{"id":9253,"date":"2020-04-23T04:32:43","date_gmt":"2020-04-23T01:32:43","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/hemograma-cu-formula-leucocitara-hbhtindici-si-reticulocite-hemoleucograma\/"},"modified":"2026-02-19T01:37:02","modified_gmt":"2026-02-18T23:37:02","slug":"hemograma-cu-formula-leucocitara-hbhtindici-si-reticulocite-hemoleucograma","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/hemograma-cu-formula-leucocitara-hbhtindici-si-reticulocite-hemoleucograma\/","title":{"rendered":"Hemogram\u0103 cu formul\u0103 leucocitar\u0103, Hb,Ht,indici \u0219i reticulocite (analiza general\u0103 a s\u00e2ngelui)"},"content":{"rendered":"<p style=\"text-align: justify;\"><em><strong>\u041e\u0431\u0449\u0430\u044f \u0438\u043d\u0444\u043e\u0440\u043c\u0430\u0446\u0438\u044f<\/strong><\/em><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hemoleucograma complet\u0103 (<strong>analiza general\u0103 a s\u00e2ngelui)<\/strong> const\u0103 din m\u0103surarea urm\u0103torilor parametrii:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">num\u0103r de leucocite;<\/span><\/li>\n<li><span style=\"font-size: medium;\">num\u0103r de eritrocite;<\/span><\/li>\n<li><span style=\"font-size: medium;\">concentra\u0163ia de hemoglobin\u0103;<\/span><\/li>\n<li><span style=\"font-size: medium;\">hematocrit;<\/span><\/li>\n<li><span style=\"font-size: medium;\">indici eritrocitari: volumul eritrocitar mediu (VEM), hemoglobin\u0103 eritrocitar\u0103 medie (HEM), concentratia medie de hemoglobin\u0103 (CHEM) si l\u0103rgimea distribu\u0163iei eritrocitare (RDW);<\/span><\/li>\n<li><span style=\"font-size: medium;\">num\u0103r de trombocite si indici trombocitari: volumul trombocitar mediu (VTM) \u015fi l\u0103rgimea distribu\u0163iei trombocitare (PDW);<\/span><\/li>\n<li><span style=\"font-size: medium;\">formul\u0103 leucocitar\u0103;<\/span><\/li>\n<li><span style=\"font-size: medium;\">+\/- num\u0103r de reticulocite.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hemograma este un test screening de baz\u0103, fiind unul din cele mai frecvent cerute teste de laborator, reprezent\u00e2nd adesea primul pas in stabilirea statusului hematologic \u015fi diagnosticul diverselor afectiuni hematologice\u00a0\u015fi nehematologice. Cuantificarea parametrilor hematologici asociat\u0103 uneori cu examinarea frotiului de s\u00e2nge aduce informa\u0163ii pre\u0163ioase, orient\u00e2nd in continuare spre efectuarea altor teste specifice<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Preg\u0103tire pacient<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hemograma se poate recolta \u00e0 jeun (pe nem\u00e2ncate) sau postprandial (trebuie totu\u015fi evitate mesele bogate in lipide care pot interfera cu anumi\u0163i parametri ai hemogramei).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Sexul, v\u00e2rsta pacientului, precum \u015fi anumite condi\u0163ii cum ar fi: starea de \u015foc, vars\u0103turi incoercibile, administrarea masiv\u0103 de lichide i.v. etc., care pot duce la deshidratarea, respectiv hiperhidratarea pacientului, precum \u015fi anumite tratamente urmate de pacient trebuie comunicate laboratorului.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Este de preferat evitarea pe c\u00e2t posibil a stresului in momentul recoltarii.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In cazul monitoriz\u0103rii regulate (zilnic sau la dou\u0103 zile) a anumitor parametrii, proba de s\u00e2nge pentru efectuarea hemogramei trebuie ob\u0163inut\u0103 \u00een acela\u015fi moment al zilei (datorit\u0103 fluctua\u0163iilor fiziologice circadiene ale unor parametri) <sup>4;6;9;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Specimen recoltat, recipient \u015fi cantitate recoltat\u0103<\/em><\/strong> \u2013 s\u00e2nge venos recoltat pe anticoagulant: EDTA tripotassium\/dipotasium\/disodium (vacutainer cu capac mov\/roz \u2013 K3 EDTA); la copii mici se poate recolta s\u00e2nge capilar din deget\/c\u0103lc\u00e2i pe heparin\u0103 (microtainer).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Se amestec\u0103 continu\u0163ul prin inversiunea u\u015foar\u0103 a tubului de circa 10 ori.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Tubul trebuie s\u0103 fie umplut cel pu\u0163in trei sferturi pentru ca raportul s\u00e2nge\/anticoagulant s\u0103 fie optim (concentra\u0163ia recomandat\u0103 de EDTA este de 1.2 \u2013 2.0 mg\/mL de s\u00e2nge) <sup>4;6;9;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Cauze de respingere a probei<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">tub incorect;<\/span><\/li>\n<li><span style=\"font-size: medium;\">specimen coagulat;<\/span><\/li>\n<li><span style=\"font-size: medium;\">specimen hemolizat;<\/span><\/li>\n<li><span style=\"font-size: medium;\">cantitate insuficient\u0103<sup>9<\/sup>.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Prelucrare necesar\u0103 dup\u0103 recoltare<\/em><\/strong> \u2013 dac\u0103 proba nu este trimis\u0103 imediat la laborator trebuie refrigerat\u0103<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Stabilitate prob\u0103 <\/em><\/strong><em>- <\/em><em>36-48 ore<\/em> la temperatura camerei (18-26\u00b0C) sau la frigider (2\u20138\u00b0C) \u2013 pentru determinarea hemoglobinei \u015fi num\u0103r\u0103torilor de celule. Este recomandat ca probele s\u0103 fie analizate \u00een primele 6 ore de la recoltare. Nu se recomand\u0103 dep\u0103\u015firea acestui interval pentru determinarea indicilor eritrocitari\u00a0\u015fi hematocritului. Dac\u0103 proba a fost refrigerat\u0103, trebuie echilibrat\u0103 la temperatura camerei inainte de a fi analizat\u0103<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metod\u0103 de determinare<\/em><\/strong> \u2013 analizor automat pe principiul citometriei in flux cu fluorescenta utiliz\u00e2nd LASER semiconductor\u00a0\u015fi focusare hidrodinamic\u0103<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Num\u0103rul de eritrocite (num\u0103rul de celule ro\u015fii) <\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Num\u0103rul de eritrocite reprezint\u0103 testul de baz\u0103 pentru evaluarea eritropoiezei. Eritrocitele sunt investigate \u00een continuare prin m\u0103surarea concentra\u0163iei de hemoglobin\u0103 \u015fi a hematocritului, iar pe baza lor analizorul calculeaz\u0103 indicii eritrocitari: VEM, HEM, CHEM \u015fi RDW, care caracterizeaz\u0103, din punct de vedere calitativ, popula\u0163ia eritrocitar\u0103.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Eritrocitele sunt cele mai numeroase celule din s\u00e2nge, sunt anucleate, fiind necesare pentru respira\u0163ia tisular\u0103. Eritrocitele sunt cele mai specializate celule ale organismului, principala func\u0163ie const\u00e2nd \u00een transportul 0<sub>2<\/sub> de la pl\u0103m\u00e2n la \u0163esuturi \u015fi transferul CO<sub>2<\/sub> de la \u0163esuturi la pl\u0103m\u00e2n. Acest lucru se realizeaz\u0103 prin intermediul hemoglobinei con\u0163inute \u00een eritrocite. Forma eritrocitelor de disc biconcav confer\u0103 raportul volum\/suprafa\u0163\u0103 optim pentru schimbul de gaze \u015fi le asigur\u0103 acestora deformabilitatea \u00een timpul travers\u0103rii microcircula\u0163iei.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>\u043f\u043e\u043a\u0430\u0437\u0430\u043d\u0438\u044f<\/em><\/strong> \u2013 \u00een combina\u0163ie cu hematocritul \u015fi concentra\u0163ia de hemoglobin\u0103, num\u0103rul de eritrocite este util \u00een detectarea \u015fi monitorizarea anemiei \u015fi eritrocitozei\/policitemiei.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metod\u0103 de determinare<\/em><\/strong> \u2013 eritrocitele sunt num\u0103rate de analizorul automat \u00een timpul trecerii acestora printr-un orificiu prin care sunt dirijate \u00eentr-un singur r\u00e2nd prin metoda de focusare hidrodinamic\u0103<sup>4;6-8;9;14;16;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referin\u0163\u0103<\/em><\/strong> \u2013 valori diferite \u00een func\u0163ie de v\u00e2rst\u0103 \u015fi sex <em>(vezi anexa 7.1.1)<\/em>; se exprim\u0103 \u00een num\u0103r de eritrocite x10<sup>6<\/sup>\/\u03bcL (mm<sup>3<\/sup>) sau num\u0103r de eritrocite x10<sup>12<\/sup>\/L<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnifica\u0163ie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Num\u0103rul de eritrocite ca singur parametru are valoare diagnostic\u0103 mic\u0103; o evaluare corect\u0103 a masei de eritrocite a organismului poate fi ob\u0163inut\u0103 doar \u00een corela\u0163ie cu hematocritul. Num\u0103rul de eritrocite este influen\u0163at de modific\u0103rile volumului plasmatic, ca de exemplu\u00a0\u00een sarcin\u0103 sau\u00a0\u00een tulbur\u0103ri ale echilibrului hidro-electrolitic<sup>4;6;14<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Sc\u0103derea num\u0103rului de eritrocite<\/span>: determin\u0103 anemie. Anemia este definit\u0103 din punct de vedere func\u0163ional printr-o mas\u0103 eritrocitar\u0103 insuficient\u0103 pentru asigurarea unei cantit\u0103\u0163i adecvate de oxigen \u0163esuturilor periferice. In practic\u0103, se consider\u0103 anemie atunci c\u00e2nd concentra\u0163ia de hemoglobin\u0103, hematocritul \u015fi\/sau num\u0103rul de eritrocite sunt sub valorile de referin\u0163\u0103<sup>7<\/sup>. Diagnosticul este dificil dac\u0103 doar unul din parametri este sub valorile limit\u0103; \u00een acest caz hemograma trebuie monitorizat\u0103 \u00een continuare pentru stabilirea unui diagnostic corect.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In anemia acut\u0103 datorat\u0103 hemoragiei, num\u0103rul de eritrocite \u015fi concentra\u0163ia de hemoglobin\u0103 r\u0103m\u00e2n nemodificate \u00een primele ore datorit\u0103 pierderii concomitente de plasm\u0103; ele \u00eencep s\u0103 scad\u0103 pe m\u0103sur\u0103 ce se produce corec\u0163ia deficitului volumic.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In anemiile cronice volumul sanguin este aproape normal prin cre\u015fterea compensatorie a volumului plasmatic, iar num\u0103rul de eritrocite\u00a0\u015fi hematocritul sunt de obicei sc\u0103zute. Totu\u015fi, \u00een condi\u0163iile asociate cu microcitoza marcat\u0103 (anemie feripriv\u0103 sever\u0103, talasemie), num\u0103rul de eritrocite poate r\u0103m\u00e2ne \u00een limite normale sau poate fi chiar crescut.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Anemia relativ\u0103 este o condi\u0163ie caracterizat\u0103 prin masa normal\u0103 de eritrocite, dar cu volum sanguin crescut prin cre\u015fterea volumului plasmatic, ca de exemplu \u00een sarcin\u0103, splenomegalie masiv\u0103. In aceast\u0103 situa\u0163ie proteinele totale plasmatice sunt la limita inferioar\u0103 a normalului, spre deosebire de anemia cronic\u0103\u00a0\u00een care proteinele totale sunt\u00a0\u00een limite normale<sup>19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Pentru a identifica cauza anemiei, informa\u0163iile privind istoricul bolii \u015fi examinarea fizic\u0103 trebuie integrate cu c\u00e2teva teste de laborator cheie, cum ar fi determinarea num\u0103rului de reticulocite, indicilor eritrocitari, examinarea frotiului de s\u00e2nge colorat \u015fi eventual a m\u0103duvei osoase. Prezen\u0163a altor anomalii hematologice (trombocitopenie, anomalii ale leucocitelor) orienteaz\u0103 diagnosticul spre o posibil\u0103 insuficien\u0163\u0103 medular\u0103 datorat\u0103 anemiei aplastice, unei boli hematologice maligne sau disloc\u0103rii m\u0103duvei osoase prin procese patologice de cauza extrahematologic\u0103. Pancitopenia poate ap\u0103rea \u015fi ca urmare a distruc\u0163iei periferice sau sechestr\u0103rii celulare prin hipersplenism.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Cre\u015fterea num\u0103rului de eritrocite<\/span> (concentra\u0163iei de hemoglobin\u0103 \u015fi\/sau hematocritului) determin\u0103 eritrocitoza. Eritrocitoza poate fi rezultatul cre\u015fterii masei eritrocitare totale (policitemie\/eritrocitoza absoluta) ori poate fi consecin\u0163a reducerii volumului plasmatic (eritrocitoza relativ\u0103\/fals\u0103)<sup>14<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>Clasificarea eritrocitozei<sup>14<\/sup><\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">A. Eritrocitoza\/policitemie relativ\u0103 (peudoeritrocitoza): hemoconcentratie; sindromul Gaisb\u0151ck.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">B. Policitemie (eritrocitoz\u0103 absolut\u0103)<\/span><\/p>\n<ol style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Policitemie primar\u0103: policitemia vera; policitemia primar\u0103 familial\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Policitemie secundar\u0103:<\/span><\/li>\n<\/ol>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Secundar\u0103 sc\u0103derii oxigen\u0103rii tisulare (eritrocitoza fiziologic\u0103\/hipoxic\u0103):<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">eritrocitoz\u0103 de altitudine;<\/span><\/li>\n<li><span style=\"font-size: medium;\">boli pulmonare: cord pulmonar cronic; hipertensiune pulmonar\u0103 primar\u0103;<\/span><\/li>\n<li><span style=\"font-size: medium;\">boli congenitale de cord cianogene;<\/span><\/li>\n<li><span style=\"font-size: medium;\">sindroame de hipoventilatie: hipoventilatie alveolar\u0103 primar\u0103; sindromul Pickwick; apneea de somn;<\/span><\/li>\n<li><span style=\"font-size: medium;\">hemoglobine anormale: ereditare\/dobandite (medicamente, substante chimice, fumat: carboxihemoglobin\u0103);<\/span><\/li>\n<li><span style=\"font-size: medium;\">policitemia familial\u0103.<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Secundar\u0103 produc\u0163iei aberante de eritropoietin\u0103 (eritrocitoz\u0103 nefiziologic\u0103):<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">boli renale: carcinomul renal \u015fi alte tumori renale; rinichiul polichistic; rinichiul in potcoav\u0103; hidronefroz\u0103; stenoz\u0103 de arter\u0103 renal\u0103;<\/span><\/li>\n<li><span style=\"font-size: medium;\">carcinomul hepatocelular \u015fi alte tumori hepatice;<\/span><\/li>\n<li><span style=\"font-size: medium;\">tumori vasculare cerebeloase;<\/span><\/li>\n<li><span style=\"font-size: medium;\">leiomiomul \u015fi tumori fibroide uterine;<\/span><\/li>\n<li><span style=\"font-size: medium;\">boli endocrine: sindrom Cushing, hiperaldosteronism primar, tumori ovariene virilizante, sindrom Barter, feocromocitom;<\/span><\/li>\n<li><span style=\"font-size: medium;\">medicamente: androgeni, abuz de eritropoietina;<\/span><\/li>\n<li><span style=\"font-size: medium;\">policitemia familial\u0103.<\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">3. Policitemie idiopatic\u0103.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferen\u0163e<\/em><\/strong> <sup>4;6;8;16;19<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. Recoltarea cu pacientul in <em>pozi\u0163ie culcat\u0103<\/em> determin\u0103 sc\u0103derea num\u0103rului de eritrocite (\u015fi hematocritului) cu 5 \u2013 10% (prin redistribuirea lichidului din spa\u0163iul intersti\u0163ial spre circula\u0163ie datorit\u0103 modific\u0103rii presiunii hidrostatice la nivelul membrelor inferioare).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <em>Stresul<\/em> poate determina cre\u015fterea num\u0103rului de eritrocite.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. <em>Staza venoas\u0103 prelungit\u0103<\/em> &gt;2 minute in timpul venopunc\u0163iei determin\u0103 cre\u015fterea num\u0103rului de eritrocite cu ~10% (\u015fi cre\u015fterea semnificativ\u0103 a hematocritului). De asemenea, recoltarea dup\u0103 <em>efort fizic intens<\/em> determin\u0103 cre\u015fterea num\u0103rului de eritrocite cu p\u00e2n\u0103 la 10% (ca \u015fi cre\u015fterea concentra\u0163iei de hemoglobin\u0103). Toate acestea se datoreaz\u0103 hemoconcentra\u0163iei.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">4. <em>Deshidratarea<\/em> cu hemoconcentra\u0163ie consecutiv\u0103 (\u015foc, arsuri severe, obstruc\u0163ie intestinal\u0103, v\u0103rs\u0103turi\/diaree persistente, abuz de diuretice) poate masca prezen\u0163a anemiei. De asemenea, <em>hiperhidratarea<\/em> pacientului (administrarea masiv\u0103 de lichide i.v.) poate determina niveluri fals sc\u0103zute ale num\u0103rului de eritrocite.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">5. Prezen\u0163a <em>aglutininelor la rece<\/em> in titru mare determin\u0103, dac\u0103 s\u00e2ngele este p\u0103strat la temperatura camerei, niveluri fals sc\u0103zute ale num\u0103rului de eritrocite \u015fiun VEM fals crescut; \u00een consecin\u0163\u0103 hematocritul este fals sc\u0103zut, iar HEM\u00a0\u015fi CHEM sunt crescute.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">6. Prezen\u0163a de <em>crioglobuline<\/em> \u00een concentra\u0163ie mare poate interfera cu determinarea num\u0103rului de eritrocite.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">7. <em>Trombocitele mari\/macrotrombocitele<\/em> (ex.: din trombocitemia esen\u0163ial\u0103) pot fi num\u0103rate ca eritrocite.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">8. Numeroase <em>medicamente<\/em> pot determina cre\u015fterea sau sc\u0103derea num\u0103rului de eritrocite:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">pot sc\u0103dea num\u0103rul de eritrocite aproape toate clasele de medicamente;<\/span><\/li>\n<li><span style=\"font-size: medium;\">pot determina cre\u015fteri ale num\u0103rului de eritrocite: corticotropina, glucocorticoizii, danazolul, eritropoietina, antitiroidienele, hidroclorotiazida, pilocarpina, mycophenolatul<sup>6<\/sup>.<\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: medium;\"><strong>Hematocritul\u00a0(volumul\u00a0pachetului\u00a0de celule)<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hematocritul m\u0103soar\u0103 raportul dintre volumul ocupat de eritrocite \u015fi volumul sanguin total.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>\u043f\u043e\u043a\u0430\u0437\u0430\u043d\u0438\u044f<\/em><\/strong> \u2013 detectarea \u015fi monitorizarea anemiei \u015fi policitemiei.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 analizorul automat calculeaz\u0103 hematocritul prin determinarea num\u0103rului de eritrocite\/L de sange \u015fi m\u0103surarea amplitudinii impulsurilor in eritrocite prin metoda luminii dispersate<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referin\u0163\u0103<\/em><\/strong> \u2013 diferite \u00een func\u0163ie de v\u00e2rst\u0103 \u015fi sex (<em>vezi anexa 7.1.1)<\/em>. Hematocritul se exprim\u0103 ca frac\u0163ie decimal\u0103\/ca procent<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnifica\u0163ie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hematocritul depinde de masa eritrocitar\u0103, volumul eritrocitar mediu \u015fi volumul plasmatic.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">De obicei, atunci cand hematiile sunt de m\u0103rime normal\u0103, modific\u0103rile hematocritului le urmeaz\u0103 pe cele ale num\u0103rului de eritrocite. Totu\u015fi \u00een anemia micro-\/macrocitar\u0103 rela\u0163ia poate s\u0103 nu se p\u0103streze. De exemplu,\u00a0\u00een talasemie hematocritul scade deoarece hematiile microcitare ocup\u0103 un volum mai mic,\u00a0\u00een timp ce num\u0103rul de eritrocite poate fi normal\/crescut<sup>8;16<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Sc\u0103derea hematocritului<\/span><span style=\"text-decoration: underline;\">: <\/span><\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2013 anemie; la un Hct &lt;30% (0.30) un pacient este moderat \u2013 sever anemic<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2013 cre\u015fterea volumului plasmatic (sarcin\u0103)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Cre\u015fterea hematocritului<\/span><span style=\"text-decoration: underline;\">:<\/span><\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2013 eritrocitoz\u0103\/policitemie<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">\u2013 hemoconcentratie (ex.: \u015foc; aport insuficient de lichide: copii mici, varstnici; poliurie etc.)<sup>8<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori critice<\/em><\/strong> -un <strong>Hct &lt;20%<\/strong> poate determina insuficien\u0163\u0103 cardiac\u0103 \u015fi deces<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 -un <strong>Hct &gt;60%<\/strong> se asociaz\u0103 cu coagularea spontan\u0103 a s\u00e2ngelui<sup>6<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferen\u0163e <\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <em>Excesul de anticoagulant<\/em> (cantitate insuficient\u0103 de s\u00e2nge) determin\u0103 sc\u0103derea volumului eritrocitar \u015fi \u00een consecin\u0163\u0103 sc\u0103derea Hct determinat manual (efect mai pronun\u0163at pentru K3-EDTA dec\u00e2t pentru K2-EDTA).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. In <em>s\u00e2ngele arterial<\/em> Hct este cu ~2% mai mare dec\u00e2t \u00een s\u00e2ngele venos.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. In <em>reticulocitoz\u0103<\/em>, <em>leucocitoz\u0103<\/em> marcat\u0103, prezen\u0163a de <em>crioglobuline<\/em> \u0438\u043b\u0438 <em>macrotrombocite<\/em> analizorul automat poate determina valori fals crescute ale Hct (volumele mai mari ale reticulocitelor \u015fi leucocitelor intr\u0103 in calculul Hct).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">4. Valori fals sc\u0103zute ale Hct pot ap\u0103rea \u00een cazuri de <em>hemoliza in vitro, autoaglutinare, microcitoz\u0103<\/em><sup>4;6;8;16;1<\/sup><sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Hemoglobina <\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hemoglobina reprezint\u0103 componentul principal al eritrocitelor (95% din proteinele citoplasmatice eritrocitare) \u015fi serve\u015fte ca vehicul pentru transportul O<sub>2<\/sub> \u015fi CO<sub>2<\/sub>. Hemoglobina este o protein\u0103 conjugat\u0103 const\u00e2nd dintr-un tetramer format din 2 perechi de lan\u0163uri polipeptidice (globine), fiecare dintre acestea fiind conjugat cu un grup hem, un complex al unui ion de fier cu pigmentul ro\u015fu, porfirina, care confer\u0103 s\u00e2ngelui culoarea ro\u015fie. Fiecare gram de hemoglobin\u0103 poate transporta 1.34 mL O<sub>2<\/sub> per 100 mL de s\u00e2nge.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hemoglobina serve\u015fte de asemenea ca tampon\u00a0\u00een lichidul extracelular. In tesuturi, la pH sc\u0103zut, O<sub>2<\/sub> se disociaz\u0103 de Hb; Hb deoxigenat\u0103 se leag\u0103 de ionii de hidrogen; \u00een eritrocite anhidraza carbonic\u0103 converte\u015fte CO<sub>2<\/sub> \u00een bicarbonat \u015fi ioni de hidrogen. Pe m\u0103sura ce ionii de hidrogen se leag\u0103 de hemoglobin\u0103, ionii bicarbonat p\u0103r\u0103sesc celula; pentru fiecare ion bicarbonat care p\u0103r\u0103se\u015fte celula intr\u0103 un ion de clor<sup>6<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Formele de hemoglobin\u0103 prezente \u00een mod normal\u00a0\u00een circula\u0163ie includ: deoxihemoglobina (HHb), oxihemoglobina (O<sub>2<\/sub>Hb), carboxihemoglobina (COHb) \u015fi methemoglobina (MetHb), toate acestea fiind determinate \u00eempreun\u0103 \u00een s\u00e2ngele total. In anumite situa\u0163ii clinice diferitele forme de Hb pot fi determinate individual<sup>19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Indicatii <\/em><\/strong><em>\u2013 \u00ee<\/em>mpreun\u0103 cu Hct \u015fi num\u0103rul de eritrocite, este util\u0103 pentru detectarea \u015fi monitorizarea anemiei \u015fi policitemiei.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 Hb este determinat\u0103 automat prin metoda fotometric\u0103 \u00een urma conversiei\u00a0\u00een SLS-Hb cu ajutorul unui surfactant Sodium Lauryl Sulfate<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong> \u2013 diferite \u00een func\u0163ie de v\u00e2rst\u0103 \u015fi sex (vezi anexa 7.1.1). Hb se exprim\u0103\u00a0\u00een g\/L sau g\/dL. In cazul exprim\u0103rii ca\u00a0\u015fi concentra\u0163ie\u00a0\u00een mmol\/L se utilizeaz\u0103 urm\u0103torii factori de conversie<sup>19<\/sup>:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">mmol\/L = g\/L x 0.0621<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">mmol\/L = g\/dL x 0.621<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">g\/dL= mmol\/L x 1.61<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">g\/L= mmol\/L x 16.1<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Num\u0103rul de eritrocite, Hb \u015fi Hct pot fi analizate aplicand \u201cregula lui trei\u201d<sup>4<\/sup>: dac\u0103 eritrocitele sunt normocitare\/normocrome: nr. Er x3 ~ valoarea Hb.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hematocritul poate fi estimat din hemoglobin\u0103 utilizand urm\u0103toarea formula:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Hct = Hb (g\/dL) x 2.8 + 0.8 sau Hct = Hb x 3<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Dac\u0103 exist\u0103 o deviere semnificativ\u0103 de la aceast\u0103 regul\u0103 trebuie verificat\u0103 existenta de anomalii ale indicilor eritrocitari \u015fi aspectul frotiului de sange<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1.<span style=\"text-decoration: underline;\">Sc\u0103derea hemoglobinei<\/span> sub nivelurile de referint\u0103 determin\u0103 aparitia anemiei. Hb trebuie evaluat\u0103 impreun\u0103 cu Hct, num\u0103rul de eritrocite, indicii eritrocitari \u015fi morfologia celular\u0103 pe frotiu pentru clasificarea anemiei. O valoare normal\u0103 a concentratiei de Hb nu exclude anemia datorat\u0103 hemoragiei acute.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In sarcin\u0103 concentratia de hemoglobin\u0103 scade cu 2\u20133 g\/dL datorit\u0103 unei cre\u015fteri disproportionate a volumului plasmatic fat\u0103 de masa eritrocitar\u0103<sup>1<\/sup><sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">La nou-n\u0103scut masa eritrocitar\u0103 este mai mare la na\u015ftere decat la adult \u015fi scade continuu in prima s\u0103pt\u0103man\u0103 de viat\u0103, Hb putand ajunge pan\u0103 la 9 g\/dL in s\u0103pt\u0103manile 11\u201312 de viat\u0103 (anemie fiziologic\u0103). Sc\u0103derea apare mai precoce \u015fi este mai pronuntat\u0103 la prematuri. Nivelurile de la adult sunt atinse in jurul varstei de 14 ani; la varstnici apare o sc\u0103dere gradual\u0103 a concentratiei de hemoglobin\u0103.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Cre\u015fterea hemoglobinei<\/span> apare in eritrocitoz\u0103\/policitemie. Dup\u0103 convietuirea un timp indelungat la altitudine survine o cre\u015ftere a Hb corespunz\u0103toare la 1 g\/dL pentru 2000 m.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori critice<\/em><\/strong> \u2013 la <strong>Hb &lt;5g\/dL<\/strong> apare insuficienta cardiac\u0103 \u015fi poate surveni decesul;<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u2013 o concentratie de <strong>Hb &gt;20 g\/dL<\/strong> poate duce la blocarea capilarelor ca urmare a hemoconcentratiei<sup>6<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. Turbiditatea serului datorat\u0103 <em>hiperlipemiei<\/em> (hipertrigliceridemiei), <em>leucocitozei<\/em> &gt;50000\/\u03bcL, <em>trombocitozei<\/em> &gt;700000\/\u03bcL sau <em>hiperproteinemiei<\/em> determin\u0103 valori fals crescute ale hemoglobinei.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. Prezenta de <em>crioglobuline<\/em> in concentratie mare poate afecta determinarea Hb (prin fenomenul de floculare).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. <em>Efortul fizic<\/em> intens poate determina cre\u015fterea Hb.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">4. Interferente medicamentoase<sup>6<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">-numeroase medicamente pot sc\u0103dea Hb;<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">-pot creste Hb: gentamicina, methyldopa<sup>4;6;8;16;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Indici Eritrocitari<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Evaluarea eritrocitelor din punct de vedere al volumului \u015fi continutului in hemoglobin\u0103 se realizeaz\u0103 prin m\u0103surarea sau calcularea urm\u0103torilor parametrii:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Volumul eritrocitar mediu <\/strong>(VEM) \u2013 reprezint\u0103 volumul ocupat de un singur eritrocit.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 VEM este calculat dup\u0103 urm\u0103toarea formul\u0103:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Hct (%) x 10<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">VEM =\u00a0\u00a0\u00a0 <span style=\"text-decoration: line-through;\">\u2014\u2014\u2014\u2014\u2014\u2014\u2013<\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Nr.Er.(x10<sup>6<\/sup>\/\u03bcL)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">VEM este determinat prin imp\u0103rtirea sumei volumelor eritrocitare la num\u0103rul de eritrocite<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103 <\/em><\/strong>\u2013 VEM se exprim\u0103 in micrometri cubi sau femtolitri (fL). La adult este cuprins intre 80 \u2013 100 fL (valori mai mari la nou-n\u0103scuti, precum \u015fi la varstnici; valori mai mici la copii pan\u0103 la 18 ani \u2013 <em>vezi anexa 7.1.1<\/em>)<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">VEM este un indice util pentru clasificarea anemiilor \u015fi poate sugera mecanismul fiziopatologic al afect\u0103rii eritrocitare. Impreun\u0103 cu ceilalti indici eritrocitari, poate permite detectarea precoce a unor procese care vor cauza anemie. VEM depinde de osmolaritatea plasmatic\u0103 \u015fi num\u0103rul diviziunilor eritrocitare.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">VEM normal<\/span><em>:<\/em> anemie normocitar\u0103 (dac\u0103 se asociaz\u0103 cu RDW &lt;15).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Clasificarea anemiilor normocitare <\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>\u00a0<\/strong>I. Anemie asociat\u0103 cu r\u0103spuns eritropoietic adecvat:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Anemie posthemoragic\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemie hemolitic\u0103 (poate fi \u015fi u\u015for macrocitar\u0103)<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">II. Anemie asociat\u0103 cu secretie sc\u0103zut\u0103 de eritropoietin\u0103:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Afectarea sursei de eritropoietin\u0103:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">Renal\u0103: anemia din insuficienta renal\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hepatic\u0103: anemia din bolile hepatice<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Reducerea stimulului (sc\u0103derea nevoilor tisulare de oxigen):<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">Anemia din insuficientele endocrine<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Malnutritia protein-caloric\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemia din bolile cronice (poate fi \u015fi microcitar\u0103)<sup>7<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">III. Anemie asociat\u0103 cu r\u0103spuns medular inadecvat:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Aplazia eritroid\u0103 pur\u0103, anemia aplastic\u0103 (pancitopenie)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli medulare infiltrative: primare hematologice sau secundare (anemia mieloftizic\u0103)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemii mielodisplazice<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemii diseritropoietice (anemia diseritropoietic\u0103 congenital\u0103 tip II)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Deficit de fier precoce<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">VEM sc\u0103zut <\/span><em>(&lt;80 fL):<\/em> anemie microcitar\u0103. Majoritatea anemiilor microcitare se datoreaz\u0103 sintezei deficitare de hemoglobin\u0103, adesea asociat\u0103 cu deficitul de fier sau cu alterarea utiliz\u0103rii fierului, precum \u015fi cu unele conditii ereditare. Datorit\u0103 acestei deficiente precursorii eritroizi parcurg mai multe diviziuni decat in mod normal, ducand la formarea de eritrocite mature de dimensiuni mai mici. RDW este &gt;15<sup>7;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Clasificarea anemiilor microcitare<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">I. Afectiuni ale metabolismului fierului:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Anemia feripriv\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemia din bolile cornice<\/span><\/li>\n<li><span style=\"font-size: medium;\">Atransferinemia congenital\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemia microcitar\u0103 hipocrom\u0103 congenital\u0103 cu suprainc\u0103rcare cu fier (sindromul Shahidi-Nathan-Diamond).<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">II. Boli ale sintezei moleculelor de globin\u0103:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Alfa- \u015fi beta- talasemia<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindroamele de hemoglobin\u0103 E (AE, EE, E-beta-talasemia)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindroamele de hemoglobin\u0103 C (AC, CC).<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hemoglobinele instabile<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">III. Boli ale sintezei de hem \u015fi porfirin\u0103:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Anemia sideroblastic\u0103 ereditar\u0103 (X-linkata, autosomala)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemia sideroblastic\u0103 dobandit\u0103 (anemia sideroblastic\u0103 idiopatic\u0103 cu sideroblasti inelari, anemia sideroblastic\u0103 asociat\u0103 cu boli mieloproliferative sau alte boli maligne)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemia sideroblastic\u0103 dobandit\u0103 reversibil\u0103 (din alcoolism, indus\u0103 de medicamente: izoniazida, cloramfenicol, din intoxicatia cu plumb \u2013 de obicei normocitar\u0103)<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Cea mai frecvent\u0103 cauz\u0103 este deficitul de fier, anemia feripriv\u0103 fiind cea mai intalnit\u0103 form\u0103 de anemie de pe glob<sup>7<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. <span style=\"text-decoration: underline;\">VEM crescut<\/span><em> (&gt;100 fL):<\/em> anemia macrocitar\u0103. Pe baza criteriilor biochimice \u015fi morfologice anemiile macrocitare se pot imparti in dou\u0103 grupuri: anemii megaloblastice\u00a0\u015fi non-megaloblastice<sup>3<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In <span style=\"text-decoration: underline;\">anemiile megaloblastice<\/span><span style=\"text-decoration: underline;\"><sup>3<\/sup><\/span> marca morfologic\u0103 este reprezentat\u0103 de prezenta precursorilor eritroizi anormali in m\u0103duva osoas\u0103, caracterizati prin dimensiuni crescute \u015fi alter\u0103ri specifice in aspectul cromatinei nucleare. Aceste celule distincte reprezint\u0103 expresia morfologic\u0103 a unei anomalii biochimice, respectiv intarzierea sintezei de ADN. Rata sintezei hemoglobinei, respectiv sinteza ARN, nu este afectat\u0103 in timp ce rata diviziunilor celulare este redus\u0103, in consecint\u0103 componentele citoplasmatice, in special Hb sunt sintetizate in exces in timpul intarzierii intre diviziunile celulare, ducand la formarea unor eritrocite de dimensiuni crescute. Cele dou\u0103 modific\u0103ri caracteristice de pe frotiul de sange care permit diferentierea anemiilor megaloblastice sunt prezenta macroovalocitelor \u015fi a neutrofilelor cu nucleu hipersegmentat. In anemia megaloblastic\u0103 VEM este de obicei &gt;110 fL (110 \u2013 130 fL, chiar pan\u0103 la 160 fL).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Clasificarea patogenic\u0103 a anemiilor megaloblastice<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>I. Deficitul de vitamin\u0103 B12<\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">A. Dieta deficitar\u0103 (rar\u0103: vegetarianismul strict, de lung\u0103 durat\u0103, f\u0103r\u0103 ou\u0103 \u015fi produse lactate; mai frecvent\u0103 la copiii n\u0103scuti din mame strict vegetariene sau la cei cu diete restrictive in fenilcetonurie).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">B. Malabsorbtie de vitamin\u0103 B12:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Anemia pernicioas\u0103 (boala autoimun\u0103 caracterizat\u0103 prin atrofie gastric\u0103 \u015fi pierderea factorului intrinsec)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Deficienta ereditar\u0103 de factor intrinsec (anemia pernicioas\u0103 ereditar\u0103)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Malabsorbtia vitaminei B12 din alimente (chirurgia gastric\u0103, pacienti cu gastrit\u0103 \u015fi aclorhidrie, infectia cu Helicobacter Pylori)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Insuficient\u0103 pancreatic\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindromul Zollinger-Ellison<\/span><\/li>\n<li><span style=\"font-size: medium;\">Competitia biologic\u0103 pentru vitamina B12: proliferarea bacterian\u0103 a intestinului subtire (anomalii structurale: diverticuli, stricturi, fistule, ansa oarb\u0103 sau ale motilitatii: disfunctia autonom\u0103 din diabet); infestarea cu Diphyllobothrium Latum<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli ileale: sprue tropical, boli intestinale inflamatorii, boala celiac\u0103, rezectii ileale, by-pass jejuno-ileal pentru obezitate, radioterapia cu afectarea ileonului, boli ileale infiltrative (limfom, sclerodermie).<\/span><\/li>\n<li><span style=\"font-size: medium;\">Malabsorbtia familial\u0103 selectiv\u0103 a vitaminei B12 (Sindromul Imerslund-Gr\u00e4sbeck)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Malabsorbtia vitaminei B12 indus\u0103 de toxice si medicamente: alcool, colchicina, metformin, neomicina, colestiramina, acid paraaminosalicilic<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">C. Defecte in tranportul \u015fi metabolismul intracelular al vitaminei B12:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Boli genetice: mutatii genetice care afecteaz\u0103 metabolismul intracelular al cobalaminei (aciduria metilmalonica \u015fi hiperhomocisteinemia); deficienta de transcobalamina II<\/span><\/li>\n<li><span style=\"font-size: medium;\">Toxicitatea oxidului nitros<sup>3;7<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>II. Deficitul de folati<\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">A. Dieta deficitar\u0103 (prematuri, dieta exclusiv lactat\u0103 la sugari f\u0103r\u0103 suplimentare cu folati, dieta restrictiv\u0103 din fenilcetonurie, abuzul de alcool)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">B. Nevoi crescute: sarcin\u0103, al\u0103ptare, copii in perioada de crestere, anemia hemolitica cronic\u0103, boli neoplazice, hipertiroidism<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">C. Pierderi crescute: dializ\u0103 cronic\u0103<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">D. Malabsorbtie de folati:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Boli intestinale: sprue tropical, boala celiac\u0103, boli intestinale inflamatorii, rezectii jejunale<\/span><\/li>\n<li><span style=\"font-size: medium;\">Dermatita herpetiform\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Aclorhidria endogen\u0103 sau iatrogenic\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Insuficienta pancreatic\u0103 in care se administreaz\u0103 terapie de substitutie oral\u0103<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">E. Deficit de folati indus toxic\/medicamentos: abuzul de alcool, sulfasalazina, anticonvulsivante (in special hidantoinele; acidul valproic), antifolati (metotrexat, trimetoprim-sulfametoxazol, pirimetamina), contraceptivele orale.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">F. Defecte mostenite ale transportului \u015fi metabolismului:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Deficitul de tetradidrofolat reductaza<\/span><\/li>\n<li><span style=\"font-size: medium;\">Malabsorbtia ereditar\u0103 de folat<\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: medium;\"><em>III. <\/em><\/span><span style=\"font-size: medium;\"><em>Boli mo\u015ftenite ale sintezei de ADN:<\/em> aciduria orotica, sindromul Lesch-Nyhan, anemia megaloblastic\u0103 responsiv\u0103 la tiamin\u0103<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>IV. Defecte ale sintezei ADN induse toxic\/medicamentos:<\/em><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Antagonisti purinici (6-mercaptopurina, 6-tioguanina, azatioprina)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antagonisti pirimidinici (citozinarabinozida)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hidroxiuree<\/span><\/li>\n<li><span style=\"font-size: medium;\">Agenti alchilanti (ciclofosfamida)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Zidovudina (AZT)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Arsenic<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>V. Cauze diverse:<\/em> eritroleucemie, leucemie acut\u0103 mieloida, sindrom mielodisplazic<sup>3;7<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><span style=\"text-decoration: underline;\">Anemiile macrocitare non-megaloblastice<\/span><span style=\"text-decoration: underline;\"><sup>7<\/sup><\/span> nu au un mecanism patogenic comun; ele reprezint\u0103 anemiile macrocitare in care precursorii eritroizi medulari sunt normali; sinteza ADN nu este afectat\u0103; VEM este de obicei, u\u015for crescut (100 \u2013 110 fL).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Clasificarea anemiilor macrocitare non-megaloblastice<\/strong><sup>7<\/sup> <\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">I. \u00a0Asociate cu eritropoieza accelerat\u0103: anemia hemolitic\u0103 \u015fi posthemoragic\u0103<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">II. Alcoolism (cre\u015fterea medie este ~5 fL, adic\u0103 5-10% peste valoarea medie a subiectilor de control; normalizarea VEM se produce dupa 3-4 s\u0103pt\u0103mani de abstinent\u0103); VEM reprezint\u0103 un test screening util pentru depistarea alcoolismului ocult.<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">III. Boli hepatice<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">IV. Sindroame mielodisplazice<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">V. Anemia mieloftizic\u0103<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">VI. Anemia aplastic\u0103<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">VII. Anemia sideroblastic\u0103 dobandit\u0103<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">VIII. Anemia diseritropoietic\u0103 ereditar\u0103 (tipurile I \u015fi III)<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">IX. Anemia Diamond-Blackfan<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">X. Hipotiroidism<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. Prezenta de <em>dubl\u0103 populatie eritrocitar\u0103<\/em> (micro- \u015fi macrocitar\u0103, cand se asociaz\u0103 anemia feripriv\u0103 cu anemia megaloblastic\u0103) poate determina un VEM normal. In aceast\u0103 situatie RDW este &gt;15, pe histograma efectuat\u0103 de analizorul automat se observ\u0103 aspectul caracteristic de \u201ccurb\u0103 cu dou\u0103 cocoa\u015fe\u201d, iar confirmarea prezentei dublei populatii eritrocitare se face prin examinarea frotiului de sange. Dubla populatie este caracteristic\u0103 pentru anemiile sideroblastice (o populatie microcitar\u0103 hipocrom\u0103 \u015fi una relativ normocitar\u0103) \u015fi anemiei feriprive dup\u0103 inceperea terapiei de substitutie cu fier.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. VEM fals crescut: <em>reticulocitoza<\/em> marcat\u0103 (&gt;50%), <em>leucocitoza<\/em> marcat\u0103 (&gt;50000\/\u00b5L) <em>hiperglicemie<\/em> marcat\u0103 (&gt;600 mg\/dl), prezenta de <em>aglutinine la rece<\/em>, intoxicatia cu <em>metanol<\/em> (\u015fi, in consecint\u0103 cre\u015fte Hct, iar CHEM scade).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. VEM fals sc\u0103zut: <em>hemoliza in vitro<\/em>, prezenta de <em>eritrocite fragmentate<\/em>, <em>excesul de EDTA<\/em>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">4. Dac\u0103 pragul inferior al analizorului este fixat prea sus, este calculat un VEM mai mare deoarece eritrocitele mai mici nu sunt m\u0103surate, iar dac\u0103 pragul superior este prea mare sunt m\u0103surate \u015fi leucocitele, iar VEM este crescut<sup>4;6;8;15;18<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Hemoglobina eritrocitar\u0103 medie <\/strong>(HEM) \u2013 este o m\u0103sura a continutului mediu de hemoglobin\u0103 pe eritrocit<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 HEM este calculat de analizorul automat conform formulei:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Hb(g\/dL) x 10<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">HEM =\u00a0\u00a0\u00a0 <span style=\"text-decoration: line-through;\">\u2014\u2014\u2014\u2014\u2014\u2014\u2013<\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Nr.Er.(x10<sup>6<\/sup>\/\u03bcL)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong> \u2013 HEM se exprim\u0103 in picograme (pg\/10<sup>-12<\/sup>g). Valorile normale la adult sunt 26\u201334 pg sau 0.4-0.53 fmol (valori mai mari la nou-n\u0103scut; <em>vezi anexa 7.1.1<\/em>).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong> \u2013 in majoritatea anemiilor HEM se coreleaz\u0103 cu VEM, astfel anemiile microcitare sunt de obicei hipocrome (uneori hipocromia poate preceda microcitoza), cele normocitare sunt de obicei normocrome, iar conditiile care cresc HEM determin\u0103 in general, dac\u0103 nu intotdeauna, VEM crescut, deoarece continutul eritrocitar normal de Hb este ~95% din concentratia de Hb maxim posibil\u0103 (anemiile macrocitare, anemia regenerativa observat\u0103 de exemplu in timpul substitutiei cu fier a anemiei feriprive, la nou-n\u0103scut)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente <\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <em>Hiperlipidemia<\/em>, <em>leucocitoza<\/em> &gt;50000\/\u03bcL determin\u0103 HEM fals crescut (Hb fals crescut\u0103)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. Concentratie crescut\u0103 de <em>heparin\u0103<\/em> determin\u0103 HEM fals crescut<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. Prezenta <em>aglutininelor la rece<\/em> determin\u0103 HEM fals crescut<sup>4;6;8;15;18<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Concentratia eritrocitar\u0103 medie de hemoglobin\u0103 <\/strong>(CHEM) \u2013 m\u0103soar\u0103 concentratia medie de Hb dintr-un volum dat de eritrocite (sau raportul dintre mas\u0103 de Hb \u015fi volumul de eritrocite)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 CHEM este calculat de analizorul automat conform formulei<sup>9<\/sup>:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Hb (g\/dL) x 100<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">CHEM =\u00a0\u00a0\u00a0 <span style=\"text-decoration: line-through;\">\u2014\u2014\u2014\u2014\u2014\u2014\u2013 <\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Hct (%)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong> \u2013 CHEM se exprim\u0103 in g\/dL. Valorile normale la adult sunt 32-36 g\/dL (320-360 g\/L)<em> (vezi anexa 7.1.1)<\/em><sup>9<\/sup><em>.<\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong> \u2013 VEM este un indice extrem de valoros in clasificarea anemiilor, dar HEM \u015fi CHEM, de obicei, nu aduc in plus informatii relevante clinic. Totu\u015fi, au un rol important in controlul de calitate al laboratorului, deoarece ace\u015fti indici variaz\u0103 foarte putin de la o zi la alta pentru un specimen dat, dac\u0103 pacientul nu este transfuzat.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Datorit\u0103 comportamentului similar al volumului eritrocitar \u015fi continutului in Hb al fiec\u0103rui eritrocit in parte, CHEM r\u0103mane constant in multe afectiuni hematopoietice<sup>4;6;8;16;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">CHEM sc\u0103zut<\/span><em> (&lt;30g\/dL):<\/em> apare in anemiile hipocrome (anemia feripriv\u0103, unele talasemii)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">CHEM crescut<\/span>: cu exceptia sferocitozei ereditare \u015fi a unor cazuri homozigote de siclemie \u015fi hemoglobina C, CHEM nu depa\u015feste valoarea de 37 g\/dL; aceast\u0103 valoare este aproape de nivelul de solubilitate a Hb \u015fi cre\u015fterea in continuare a concentratiei de Hb poate duce la cristalizarea ei. Acuratetea determin\u0103rii CHEM depinde de factorii care afecteaz\u0103 m\u0103surarea fie a Hct, fie a Hb.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. CHEM poate fi fals crescut in <em>hiperlipemie<\/em>, prezenta de <em>aglutinine la rece<\/em> in titru mare, prezenta de <em>rulouri<\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. In <em>hiperglicemia<\/em> marcat\u0103 (&gt;600 mg\/dL) CHEM poate fi fals sc\u0103zut (VEM si Hct fals crescute) <sup>4;6;8;16;19<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>L\u0103rgimea distributiei eritrocitare <\/strong>(RDW) \u2013 este un indice eritrocitar care cuantific\u0103 heterogenitatea volumului celular (gradului de anizocitoz\u0103)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 RDW este calculat de analizorul automat in functie de prezenta de anomalii ale frecventei relative la anumite niveluri de discriminare, existenta a dou\u0103 sau a mai multor \u201cpeak\u201d-uri \u015fi l\u0103rgime de distributie anormal\u0103. Distributia VEM intr-o proba este prezentat\u0103 sub forma unui grafic in care pe abscisa se proiecteaz\u0103 volumul eritrocitar, iar pe ordonat\u0103 frecventa relativ\u0103<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Deviatia standard a m\u0103rimii eritrocitelor x 100<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">RDW (CV%) =\u00a0\u00a0 <span style=\"text-decoration: line-through;\">\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014-<\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 VEM<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong> \u2013 11.6-14.8 coeficient de variatie (CV) a volumului eritrocitar<sup>9<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">RDW este util in caracterizarea initial\u0103 a anemiilor, in particular a anemiei microcitare, de\u015fi alte teste sunt de obicei necesare pentru confirmarea diagnosticului. Astfel RDW este util in diferentierea beta-talasemiei minore necomplicate, in care VEM este sc\u0103zut, iar RDW normal de anemia feripriv\u0103, in care VEM este sc\u0103zut, iar RDW crescut (cre\u015fterea RDW este un semn precoce in deficitul de fier)<sup>7<\/sup>. RDW este usor crescut in beta-talasemia minor\u0103 cu anemie u\u015foar\u0103<sup>4<\/sup> . Unele studii au ar\u0103tat\u00a0c\u0103 RDW nu diferentiaz\u0103 beta-talasemia minor\u0103 de anemia feripriv\u0103 decat dac\u0103 este utilizat un cut-off mai mare (17%)<sup>4<\/sup>. De asemenea permite diferentierea intre anemia din bolile cronice (VEM normal\/sc\u0103zut, RDW normal) \u015fi anemia feripriv\u0103 incipient\u0103 (VEM normal\/sc\u0103zut, RDW crescut)<sup>7;16<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><span style=\"text-decoration: underline;\">RDW crescut<\/span><em>: <\/em>anemia feripriv\u0103, anemia megaloblastic\u0103, diferite hemoglobinopatii (S, S-C, S-\u03b2-talasemia), anemia hemolitic\u0103 imun\u0103, reticulocitoza marcat\u0103, prezenta de fragmente eritrocitare, aglutinare, dimorfism eritrocitar (inclusiv pacientii transfuzati sau cei tratati recent pentru deficiente nutritionale)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><span style=\"text-decoration: underline;\">RDW normal<\/span><span style=\"text-decoration: underline;\">:<\/span> anemia din bolile cronice, beta-talasemia heterozigota, anemia hemoragic\u0103 acut\u0103, anemia aplastic\u0103, sferocitoza ereditar\u0103, boala cu Hb E, siclemia<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Nu exist\u0103 o cauz\u0103 cunoscut\u0103 pentru RDW sc\u0103zut<sup>4;6;8;16;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong>:<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">1. <em>Alcoolismul<\/em> cre\u015fte RDW<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">2. Prezenta <em>aglutininelor la rece<\/em><sup>4;6;8;16<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>\u00a0<\/strong><\/span><span style=\"font-size: medium;\"><strong>Reticulocitele <\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Reticulocitele sunt eritrocite anucleate tinere, imature, care contin acizi nucleici reziduali (ARN). Dup\u0103 expulzarea nucleului eritrocitele r\u0103man in m\u0103duv\u0103 pan\u0103 la 4 zile, timp in care are loc o sc\u0103dere continu\u0103 a num\u0103rului de poliribozomi (care contin ARN) \u015fi a sintezei de hemoglobin\u0103. Aceste eritrocite tinere se maturizeaz\u0103 complet in circulatia periferic\u0103 in circa 1-2 zile dup\u0103 ce p\u0103r\u0103sesc m\u0103duva osoas\u0103, timp in care pierd complet capacitatea de sintez\u0103 proteic\u0103 (respectiv poliribozomii care contin ARN), iar sinteza de Hb inceteaz\u0103. Reticulocitele apar pe frotiul colorat Wright-Giemsa ca celule policromatofile (materialul nucleic reticular se coloreaz\u0103 in albastru-gri) de volum mai mare decat cel al eritrocitelor mature. Materialul reticular se coloreaz\u0103 cu coloranti supravitali ca albastru cresil briliant\/albastru de metilen. In mod normal, in absenta anemiei, un num\u0103r mic de reticulocite este prezent in circulatie (in fiecare zi ~1% din eritrocite sunt inlocuite cu eritrocite tinere eliberate din m\u0103duv\u0103). Determinarea num\u0103rului de reticulocite ofer\u0103 informatii despre capacitatea medular\u0103 de a sintetiza celule rosii ca r\u0103spuns la o suprasolicitare fiziologic\u0103, cum este anemia<sup>4;6-8;16;19<\/sup>. <\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Indicatii<\/em><\/strong>:<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">1. Diferentierea tipurilor de anemii in: neregenerative \u015fi regenerative\/hiper-regenerative<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">2. Monitorizarea r\u0103spunsului la tratamentul de sustitutie cu fier, acid folic\/vitamina B12<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">3. Evaluarea eritropoiezei dup\u0103 transplant medular, in anemia aplastic\u0103 indus\u0103 de medicamente citotoxice\/sau in tratamentul cu eritropoietin\u0103<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">1. Metoda manual\u0103 \u2013 num\u0103rare microscopic\u0103<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">2. Num\u0103rarea automat\u0103 \u2013 analizor automat pe principiul citometriei in flux cu fluorescent\u0103 \u015fi LASER semiconductor<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Adult: 0.5-2% din nr. total de Er.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Nou-n\u0103scut: 2.5-6.5% din nr. total de Er (scade la nivelul de la adult din a doua s\u0103pt\u0103man\u0103 de viat\u0103)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Nr. absolut = 30-120 x 10<sup>3<\/sup>\/\u03bcL sau x 10<sup>9<\/sup>\/L.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In prezenta anemiei nr. de Rt trebuie corectat deoarece este fals crescut cand se raporteaz\u0103 la nr. sc\u0103zut de Er al pacientului anemic<sup>5;7<\/sup>:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">`\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 %Rt x Hct pacientului<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">% Rt corectat = <span style=\"text-decoration: line-through;\">\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014-<\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 45<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In continuare trebuie f\u0103cut\u0103 o corectie suplimentar\u0103 deoarece Rt eliberate sub stimularea intens\u0103 a eritropoietinei r\u0103man in circulatie un timp aproximativ dublu fat\u0103 de timpul de supravietuire al Rt normale (aproximativ o zi). Se calculeaz\u0103 astfel <em>indicele de productie reticulocitar\u0103<\/em> <em>(IPR)<\/em><em><sup>5<\/sup><\/em> din %Rt corectat \u015fi un factor de corectie care depinde de Hct pacientului:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium; text-decoration: underline;\">Hct (%)\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Factor de corectie<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">40-45\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 1.0<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">35-39\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a01.5<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">25-34\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 2.0<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">15-24\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a02.5<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">&lt;15\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 3.0<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>IPR<\/em> = % Rt corectat\/factorul de corectie<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Un IPR &lt;2 indic\u0103 un r\u0103spuns medular inadecvat, in timp ce un IPR &gt;2 sugereaz\u0103 c\u0103 m\u0103duva osoas\u0103 r\u0103spunde adecvat gradului de anemie<sup>5<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103 <\/em><\/strong>\u2013 determinarea nr. relativ sau absolut de Rt reprezint\u0103 un indicator important al activit\u0103tii eritropoietice medulare, furnizand o apreciere initial\u0103 dac\u0103 anemia se datoreaz\u0103 alter\u0103rii productiei eritrocitare sau pierderii de eritrocite in circulatie (prin sangerare sau hemoliz\u0103) <sup>1;4;5<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Num\u0103r crescut de reticulocite (reticulocitoza<\/span>): este indicator de eritropoiez\u0103 regenerativ\u0103 (cresterea productiei eritrocitare medulare sub actiunea eritropoietinei; sub stimulare maxim\u0103 m\u0103duva poate produce eritrocite de 6-8 ori mai mult fat\u0103 de rata normal\u0103).<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Hemoragia acut\u0103: debutul \u015fi gradul reticulocitozei depind de cantitatea de sange pierdut\u0103; de obicei, reticulocitoza apare in a 2<sup>a <\/sup>\u2013 a 3<sup>a<\/sup> zi \u015fi ajunge pan\u0103 la 5-15%<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemia hemolitic\u0103: anemia hemolitic\u0103 imun\u0103 (test Coombs +) idiopatic\u0103 sau secundar\u0103, transfuzii de sange incompatibil, boli hemolitice ereditare (defecte membranare eritrocitare: sferocitoz\u0103 ereditar\u0103, eliptocitoz\u0103 ereditar\u0103 etc.; defecte enzimatice: deficit de glucozo-6-fosfat dehidrogenaz\u0103, deficit de piruvat kinaz\u0103 etc.), hemoglobinopatii (siclemie, sindroame talasemice etc.), anemii hemolitice dobandite (anemia hemolitic\u0103 microangiopatic\u0103; infectii: malarie, clostridii; agenti chimici si medicamente oxidante\/neoxidante; hemodializ\u0103; veninuri; hemoglobinuria paroxistica nocturn\u0103; anemia hemolitic\u0103 cu acantocite din bolile hepatice)<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Sindroamele hemolitice usoare se pot asocia cu concentratii normale de Hb \u015fi reticulocitoz\u0103 de 2-5%.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Anemiile hemolitice acute se pot asocia cu reticulocitoz\u0103 de &gt;50%.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In hipersplenism este prezent\u0103 o anemie hemolitic\u0103 u\u015foar\u0103 cu num\u0103r de Rt u\u015for crescut.<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Tratamentul de substitutie cu fier, acid folic\/vitamina B12 al anemiilor deficitare in ace\u015fti factori: regenerarea eritropoiezei este marcat\u0103 intr-o s\u0103pt\u0103man\u0103 de tratament de cre\u015fterea num\u0103rului de Rt, iar o reticulocitoz\u0103 maxim\u0103 de 10-20% apare dup\u0103 2-4 s\u0103pt\u0103mani de tratament<\/span><\/li>\n<li><span style=\"font-size: medium;\">Tratamentul cu eritropoietin\u0103: o cre\u015ftere u\u015foar\u0103 a nr. de Rt apare dup\u0103 24 ore (cu eliberarea din m\u0103duv\u0103 de Rt imature, mari, cu continut mare de ARN), nivelul maxim este atins dup\u0103 4-6 zile, iar normalizarea survine dup\u0103 8-10 zile<\/span><\/li>\n<li><span style=\"font-size: medium;\">Aplazia medular\u0103 indus\u0103 de medicamente citotoxice: o cre\u015ftere a nr. de Rt poate precede alti parametrii hematologici cu cateva zile<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Num\u0103r sc\u0103zut de reticulocite (reticulocitopenia)<\/span>: apare in anemii non-regenerative, cum ar fi deficitul de fier\/folat\/vitamina B12, aplazia medular\u0103 (deficitul persistent de Rt sugereaz\u0103 un prognostic prost), anemia din bolile cronice, insuficienta medular\u0103 (anemia mieloftizica).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Determinarea num\u0103rului de Rt are important\u0103 in special in anemia normocitar\u0103. Anemia microcitar\u0103 cu feritin\u0103 \u015fi saturatie a transferinei normale\u00a0\u015fi nr. de Rt crescut sugereaz\u0103 o hemoglobinopatie. Reticulocitoza in combinatie cu anemia macrocitar\u0103 sugereaz\u0103 deficit de folat\/vitamina B12 partial tratat, iar anemia hemolitic\u0103 poate fi u\u015for macrocitar\u0103<sup>4;5<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Unele analizoare furnizeaz\u0103 un parametru suplimentar: <strong>fractia reticulocitelor imature (IRF)<\/strong>. Stabilirea indexului de maturitate a reticulocitelor furnizeaz\u0103 informatii complementare num\u0103rului de reticulocite in evaluarea activit\u0103tii eritropoietice.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">IFR reprezint\u0103 procentul de reticulocite care au un continut crescut sau intermediar de ARN. <\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valorile de referint\u0103<\/em><\/strong> specifice metodei de lucru a laboratorului nostru sunt diferite in functie de sex:<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">b\u0103rbati: 2.3-13.4%<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">femei: 3.0-15.9%.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Studiile efectuate au ar\u0103tat faptul c\u0103 IRF constituie un indicator mai sensibil \u015fi mai specific decat num\u0103rul de reticulocite determinat izolat, in urm\u0103toarele situatii clinice:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">monitorizarea regener\u0103rii medulare post transplant\u00a0 sau chimioterapie (ex. IRF scade la 2-3 zile dup\u0103 incheierea chimioterapiei \u015fi cre\u015fte inainte de o noua cur\u0103);<\/span><\/li>\n<li><span style=\"font-size: medium;\">monitorizarea succesului transplantului renal (instalarea productiei de eritropoietina);<\/span><\/li>\n<li><span style=\"font-size: medium;\">monitorizarea tratamentului anemiilor cu fier, vitamina B12 \u015fi folati;<\/span><\/li>\n<li><span style=\"font-size: medium;\">monitorizarea tratamentului cu eritropoietina la copii, pacienti cu insuficient\u0103 renal\u0103 cronic\u0103, sindrom mielodisplazic, SIDA;<\/span><\/li>\n<li><span style=\"font-size: medium;\">monitorizarea efectelor toxice medulare induse de AZT;<\/span><\/li>\n<li><span style=\"font-size: medium;\">evaluarea anemiilor normocrome de diverse etiologii;<\/span><\/li>\n<li><span style=\"font-size: medium;\">diagnosticul \u015fi monitorizarea anemiilor aplastice;<\/span><\/li>\n<li><span style=\"font-size: medium;\">detectia crizei aplastice in anemiile hemolitice;<\/span><\/li>\n<li><span style=\"font-size: medium;\">stabilirea momentului prelev\u0103rii de celule stem dup\u0103 tratamentul cu factori de cre\u015ftere sau chimioterapie;<\/span><\/li>\n<li><span style=\"font-size: medium;\">detectia hemoragiilor oculte sau a anemiilor hemolitice compensate;<\/span><\/li>\n<li><span style=\"font-size: medium;\">estimarea hipoxiei cronice in afectiuni pulmonare sau cardiopatii cianogene (este indus\u0103 o activitate eritropoietic\u0103 crescut\u0103);<\/span><\/li>\n<li><span style=\"font-size: medium;\">clasificarea anemiilor.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Referitor la clasificarea anemiilor, in tabelul de mai jos sunt prezentate modific\u0103rile num\u0103rului absolut de reticulocite \u015fi al FRI in diverse tipuri de anemie:<\/span><\/p>\n<table class=\"wp-block-table w-100\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\"><strong>Conditii clinice<\/strong><\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\"><strong>Numar reticulocite<\/strong><\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\"><strong>Fractia reticulocitelor imature<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Aplazie medulara, criza aplastica in anemii hemolitice<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Anemii hipoplazice<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Regenerare medulara<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2191 sau N<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Boli cronice<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193 sau N<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Deficit de fier<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193 sau N<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2191<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Deficit de folat sau vit. B12<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2193 sau N<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2191<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Talasemii<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">N sau \u2191<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">N sau \u2191<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Mielodisplazii<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Variabil<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">N sau \u2191<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Anemii hemolitice<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2191<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2191<\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: left;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">Hemoragie sau anoxie<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">N sau \u2191<\/span><\/td>\n<td style=\"text-align: center;\" valign=\"top\" width=\"197\"><span style=\"font-size: medium;\">\u2191<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In concluzie, IRF corelat cu num\u0103rul de reticulocite constituie un indicator util al activit\u0103tii eritropoietice, furnizand informatii similare cu indicele productiei reticulocitare (IPR), care fiind ins\u0103 un\u00a0 parametru calculat \u015fi nu un rezultat al m\u0103sur\u0103rii directe poate fi inlocuit de acestea<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Numarul\u00a0de\u00a0trombocite <\/strong>(numarul de plachete) <strong>\u00a0<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Trombocitele sunt fragmente citoplasmatice anucleate bogate in granule, rotund-ovalare, plate, in form\u0103 de disc, cu diametrul de 2-4\u03bc. Trombopoieza are loc in m\u0103duva osoas\u0103 incepand cu celula progenitoare multipotent\u0103, continu\u0103 cu megakariocitopoieza care include proliferarea megakariocitar\u0103 \u015fimaturarea megakariocitelor cu formarea de trombocite. In mod normal, dou\u0103 treimi din trombocite se g\u0103sesc in circulatie, iar o treime sunt stocate in splin\u0103. Trombocitele sunt implicate in hemostaz\u0103 \u015fi in initierea proceselor de reparare tisular\u0103 \u015fi vasoconstrictie dup\u0103 injuria vascular\u0103 \u015fi in timpul proceselor inflamatorii, aderarea \u015fi agregarea plachetar\u0103 avand ca rezultat formarea trombusului plachetar care astup\u0103 rupturile din peretii vaselor mici.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Indicatii<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">investigarea unei sanger\u0103ri neexplicate, unei boli hemoragice sau a unei boli trombotice<\/span><\/li>\n<li><span style=\"font-size: medium;\">in cadrul unui profil de coagulare<\/span><\/li>\n<li><span style=\"font-size: medium;\">monitorizarea bolilor asociate cu insuficient\u0103 medular\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">monitorizarea in timpul tratamentelor care pot induce supresie medular\u0103 (iradiere, chimioterapie etc.) <sup>4;6<\/sup><sup>;<\/sup><sup>8;10;12-14;16;17;19<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 trombocitele sunt num\u0103rate de analizorul automat prin aceea\u015fi metod\u0103 ca eritrocitele, in timpul direction\u0103rii lor intr-un singur rand printr-un orificiu, prin metoda de focusare hidrodinamic\u0103<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">O estimare a num\u0103rului de trombocite pe un frotiu de sange bine efectuat constituie un control valoros al num\u0103rului de trombocite determinat prin metoda automat\u0103. In general, cand frotiul este examinat cu obiectivul de 100x fiecare trombocit observat\/camp reprezint\u0103 ~10000 Tr x10<sup>6<\/sup>\/L. In consecint\u0103, un frotiu normal trebuie s\u0103 prezinte in medie cel putin 14 Tr\/camp<sup>15<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong><sup>9 <\/sup>\u2013 150-450 x 10<sup>3<\/sup>\/\u03bcL.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Cre\u015fterea num\u0103rului de trombocite (trombocitoza\/trombocitemie)<\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">A. Trombocitoza tranzitorie \u2013 se datoreaz\u0103 mobiliz\u0103rii trombocitelor din pool-ul extravascular: efort fizic, na\u015ftere, administrare de epinefrina<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">B. Trombocitoza primar\u0103:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Trombocitemia ereditar\u0103 (rar\u0103; autosomal dominant\u0103; mutatie a genei trombopoietinei de pe cromozomul 3)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindroame mieloproliferative (hematopoieza clonal\u0103): trombocitemia esential\u0103, policitemia vera, leucemia mieloid\u0103 cronic\u0103, metaplazia mieloid\u0103 cu mielofibroz\u0103<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">C. Trombocitoza secundar\u0103\/reactiv\u0103 (productia persistent\u0103 a unuia sau mai multor factori trombopoietici, in special interleukina 6, care actioneaz\u0103 asupra megakariocitelor):<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">boli infectioase<\/span><\/li>\n<li><span style=\"font-size: medium;\">boli inflamatorii<\/span><\/li>\n<li><span style=\"font-size: medium;\">boli maligne<\/span><\/li>\n<li><span style=\"font-size: medium;\">regenerarea rapid\u0103 dup\u0103 hemoragie\/anemie hemolitic\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">rebound dup\u0103 refacerea post-trombocitopenie<\/span><\/li>\n<li><span style=\"font-size: medium;\">asplenia anatomic\u0103 (splenectomie)\/functional\u0103 (de exemplu din siclemie)<\/span><\/li>\n<li><span style=\"font-size: medium;\">deficitul de fier<\/span><\/li>\n<li><span style=\"font-size: medium;\">postchirurgical<sup>13<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In sindroamele mieloproliferative cronice trombocitoza este frecvent\u0103 \u015fi poate constitui un mecanism fiziopatologic important in producerea hemoragiei\u00a0\u015fi trombozei. Trombocitele circulante sunt mari, dismorfice\u00a0\u015fi anormale functional. Pacientii cu trombocitoza reactiv\u0103 pot avea valori ale trombocitelor la fel de mari ca in bolile mieloproliferative (de ordinul milioanelor), dar hemoragia\u00a0\u015fi tromboza sunt neobisnuite. Trombocitele circulante sunt mari, rotunde, normale functional<sup>4;13<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Sc\u0103derea num\u0103rului de trombocite (trombocitopenia)<\/span>: este cea mai frecvent\u0103 cauz\u0103 de sangerare. Trombocitopenia poate ap\u0103rea prin mecanisme diferite:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">A. Distructie accelerat\u0103 a trombocitelor: este cea mai frecvent\u0103 cauz\u0103 de trombocitopenie; aceasta determin\u0103 stimularea trombopoiezei ducand la cresterea num\u0103rului, m\u0103rimii \u015fi maturatiei megakariocitelor medulare<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Datorat\u0103 unor procese imunologice:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">autoimune: idiopatic\u0103\/secundar\u0103 (infectii, sarcin\u0103, boli vasculare de colagen, boli limfoproliferative, tumori solide, medicamente etc.); mecanismul este reprezentat de prezenta de autoanticorpi anti-trombocitari de tip IgG \u015fi\/sau IgA, mai rar IgM, care activeaz\u0103 complementul \u015fi determin\u0103 scurtarea duratei de viat\u0103 a trombocitelor prin indep\u0103rtarea din circulatie de c\u0103tre sistemul fagocitic mononuclear splenic<\/span><\/li>\n<li><span style=\"font-size: medium;\">aloimune: trombocitopenie neonatal\u0103; purpura posttransfuzional\u0103<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Datorat\u0103 unor procese non-imunologice:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">microangiopatii trombotice: coagulare intravasculara diseminat\u0103, purpura trombotic\u0103 trombocitopenic\u0103, sindrom hemolitic uremic, sindromul HELLP din sarcin\u0103 (hemoliza\/eclampsie, cresterea enzimelor hepatice \u015fi sc\u0103derea trombocitelor)<\/span><\/li>\n<li><span style=\"font-size: medium;\">alterarea trombocitelor prin suprafete vasculare anormale (valvulopatii, ateroscleroz\u0103 extensiv\u0103, proteze vasculare, catetere, circulatie extracorporeal\u0103 etc.)<\/span><\/li>\n<li><span style=\"font-size: medium;\">infectii: virusuri (rubeol\u0103\/oreion neonatal, citomegalovirus, parvovirus B19, vaccinuri), bacterii (septicemie, meningococemie, boala Lyme), Mycoplasma pneumoniae, protozoare (malarie)<\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">B. Productie sc\u0103zut\u0103 de trombocite:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Hipoplazie megakariocitara: medicamente mielosupresive (agenti alchilanti, antimetaboliti, medicamente citotoxice), radiatii ionizante, anemie aplastic\u0103, boli medulare infiltrative, medicamente care produc hipoplazie medular\u0103 prin mecanism idiosincrazic (cloramfenicol), substante care supreseaz\u0103 selectiv megakariocitele (clorotiazide, estrogeni, etanol)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Trombopoiez\u0103 ineficient\u0103: anemia megaloblastic\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Alterarea mecanismului de reglare a trombopoiezei: deficit de trombopoietin\u0103; trombocitopenia ciclic\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">Trombocitopenii ereditare: trombocitopenia amegakariocitara congenital\u0103, trombocitopenia cu absenta radiusului, anomalia May-Hegglin, sindromul Wiskott-Aldrich (microtrombocitopenia X-linkata), macrotrombocitopenia X-linkata cu diseritropoieza, sindromul Bernard-Soulier, sindromul plachetelor gri etc.<\/span><\/li>\n<li><span style=\"font-size: medium;\">Purpura trombocitopenic\u0103 amegakariocitara pur\u0103 dobandit\u0103 (rar\u0103)<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">C. Distributie anormal\u0103 a trombocitelor:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Boli ale splinei (neoplazice, congestive, infiltrative, infectioase); de obicei trombocitopenie u\u015foar\u0103 = 50-100\u00d710<sup>3<\/sup>\/\u03bcL<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hipotermia<\/span><\/li>\n<li><span style=\"font-size: medium;\">Dilutia trombocitelor prin transfuzii masive<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Numeroase medicamente au fost asociate cu trombocitopenia imun\u0103. Cele mai comune medicamente incriminate sunt: heparina (1% din pacienti), quinidina, quinina, rifampicina, trimetoprim-sulfametoxazol, danazol, metildopa, acetaminofen, digoxin, interferon-alfa etc.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Trombocitopenia se asociaz\u0103 clinic cu sangerari cutaneo-mucoase: petesii, purpura, gingivoragii, epistaxis, pan\u0103 la sangerari gastrointestinale, pulmonare \u015fi genitourinare. Sanger\u0103rile spontane sunt rare la &gt;60\u00d710<sup>3<\/sup>Tr\/\u03bcL (pot ap\u0103rea sanger\u0103ri posttraumatice, postoperatorii) <sup>12;17<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em><span style=\"color: #ff0000;\">Valori critice<\/span><\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #ff0000; font-size: medium;\">1. Trombocitoza <strong>&gt;1.5\u00d710<sup>9<\/sup>\/<\/strong><strong>\u03bc<\/strong><strong>\u041c<\/strong>, precum \u015fi trombocitoza la pacienti varstnici \u015fi\/sau cu boli cardiovasculare prezint\u0103 risc de tromboz\u0103, mai rar de hemoragie<sup>6<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #ff0000; font-size: medium;\">2.\u00a0 Trombocitopenia <strong>&lt;20\u00d710<sup>3<\/sup>\/<\/strong><strong>\u03bc<\/strong><strong>\u041c<\/strong> se asociaz\u0103 cu risc de sanger\u0103ri spontane interne\/externe (risc 1% de hemoragii intracraniene)<sup>6<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente <\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. Trombocitele cresc la altitudine, in timpul iernii, dup\u0103 efort fizic intens, traume<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. Trombocitele scad inaintea menstruatiei \u015fi in sarcin\u0103<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. O <em>fals\u0103 trombocitopenie<\/em> poate fi indicat\u0103 de analizorul automat \u015fi se datoreaz\u0103 unei erori de num\u0103rare:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">formarea de agregate\/aglutinate trombocitare (<em>pseudotrombocitopenie<\/em>) induse de anticoagulantul EDTA \u2013 se datoreaza prezentei de aglutinine (autoanticorpi), care sunt imunoglobuline de tip IgG, IgA\/IgM \u015fi care induc aglutinarea <em>in vitro<\/em> a trombocitelor dependente de anticoagulant (care induce expunerea unor situsuri antigenice la care se vor lega anticorpii); nu exista nici o asociere cunoscuta cu vreo boala\/medicament; este cea mai frecventa cauza de falsa trombocitopenie. Frotiul de sange periferic evidentiaza agregatele trombocitare; pentru o numaratoare exacta a trombocitelor se recomanda recoltarea unei picaturi de sange din pulpa degetului \u015fi folosirea modulului capilar al analizorului<\/span><\/li>\n<li><span style=\"font-size: medium;\">prezenta de trombocite gigante<\/span><\/li>\n<li><span style=\"font-size: medium;\">satelitismul plachetar (absorbtia trombocitelor pe suprafata neutrofilelor segmentate)<\/span><\/li>\n<li><span style=\"font-size: medium;\">prezenta aglutininelor la rece care poate determina aglutinare independenta de EDTA<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">4. Prezenta de fragmente eritrocitare, microsferocite, fragmente leucocitare (fragmente nucleare \u015fi citoplasmatice limfocitare in leucemia limfoida cronica) poate determina niveluri fals crescute ale trombocitelor<sup>4;6;8;16;17;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>5. Interferente medicamentoase:<\/em><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\"><strong>Cresc trombocitele<\/strong>: cefazolin, ceftriaxon, clindamicin, danazol, diltiazem, dipiridamol, epoetin alfa, eritropoietina, fludarabina, gemfibrozil, glucocorticoizi, imipenem, imunoglobuline, interferon alfa-2a, isotretinoin, lansoprazol, litiu, lomefloxacin, megestrol, meropenem, metilprednisolon, metoprolol, miconazol, moxalactam, netilmicina, ofloxacina, contraceptive orale, penicilamina, propranolol, steroizi, ticlopidina, zalcitabina, zidovudina<sup>6<\/sup>.<\/span><\/li>\n<li><span style=\"font-size: medium;\"><strong>Scad trombocitele<\/strong>: abciximab, acetaminofen, acetazolamida, albendazol, albuterol, alemtuzumab, alopurinol, acid aminocaproic, aminoglutetimid, amiodarona, amitriptilina, amoxicilina, amfotericina B, ampicilina, amrinona, anagrelid, anticonvulsivante, antineoplazice, trioxid de arseniu, asparaginaza, aspirina, aur, azatioprina, azitromicina, barbiturice, vaccin BCG, benazepril, betaxolol, subsalicilat de bismut, bleomicina, candesartan, capecitabina, captopril, carbamazepin, carbenicilin, carmustina, carvedilol, cefaclor, cefamandol, cefazolin, cefoxitin, ceftriaxon, cefuroxim, clorambucil, cloramfenicol, clordiazepoxid, clorochina, clorotiazida, clorfeniramin, clorpromazina, clorpropamid, cimetidina, cladribina, clindamicina, clofibrat, clonazepam, clopidogrel, cotrimoxazol, codeina, colchicina, ciclofosfamida, citarabina, dacarbazina, dalteparin, danazol, diazoxid, diclofenac, didanozina, dietilstilbestrol, digitala, digoxin, diltiazem, difenhidramina, disopiramida, docetaxel, doxepin, doxorubicin, doxiciclina, enalapril, epirubicin, eprosartan, eritromicina, esomeprazol, etanercept, acid etacrinic, etosuximid, etidronat, etopozid, etretinat, factor VIIa, famotidina, fenoprofen, flecainida, fluconazol, flucitozin, fludarabina, 5-fluorouracil, flufenazin, fluvastatin, fondaparinux, furosemid, gabapentin, ganciclovir, gemcitabina, gentamicina, glimepirid, gliburid, granisetron, vaccin antihepatita B, hidralazina, hidroclorotiazida, hidroxiclorochina, hidroxiuree, ibuprofen, idarubicina, ifosfamida, imatinib, imipenem, imipramina, imunoglobulina, indinavir, indometacin, infliximab, interferon alfa-2a, interleukina-2, irinotecan, isoniazida, isosorbid, isotretinoin, itroconazol, ketoprofen, lamivudina, lansoprazol, lepirudin, levamizol, levodopa, lisinopril, lomefloxacin, lomustin, lovastatin, loxapin, vaccin antirubeolic, vaccin antirujeolic, mecloretamina, acid mefenamic, meloxicam, melfalan, meprobamat, 6-mercaptopurina, meropenem, mesalamina, metformin, metazolamida, meticilina, metotrexat, metsuximid, metildopa, metisergid, metoprolol, metronidazol, milrinona, mitoxantrona, moricizina, morfina, moxalactam, micofenolat, acid nalidixic, naproxen,\u00a0 netilmicina, nicardipina, nitrofurantoin, nitroglicerina, nizatidina, norfloxacin, nortriptilina, nistatin, ofloxacin, paclitaxel, pamidronat, penicilamina, penicilina, pentamidina, pentostatin, pentoxifilina, fenobarbital, fenotiazine, indolol, piroxicam, vaccin antipolio, pravastatin, prednison, probenecid, procainamida, procarbazina, promazina, prometazina, propafenona, propranolol, protriptilina, pirazinamida, pirimetamina, raloxifen, ramipril, rezerpina, rifampicina, vaccin antirubeolic, sargramostin, spironolactona, stavudin, streptomicin, sulfametoxazol, sulfasalazina, sulfoniluree, sulindac, tacrolimus, tamoxifen, tetraciclina, tiabendazol, tiazide, tioguanina, tioridazina, tiotepa, ticarcilina, ticlopidina, timolol, tinzaparin, tobramicina, tocainida, tolbutamid, tolmentin, topotecan, trimetoprim, vaccin antiurlian, acid valproic, vancomicina, vinblastina, vincristina, vinorelbina, zidovudina<sup>6<\/sup>.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Volumul trombocitar\u00a0mediu <\/strong>(VTM)<sup>4;6;16;17<\/sup> \u2013 indic\u0103 uniformitatea de m\u0103rime a populatiei trombocitare. Este util in diagnosticul diferential al trombocitopeniei<sup>4;6;16;17<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong>: este calculat de analizorul automat dup\u0103 urm\u0103toarea formul\u0103:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 PCT (Plachetocrit) (%)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">VTM (fL) = <span style=\"text-decoration: line-through;\">\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014\u2014-<\/span> x1000<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>\u00a0<\/strong>\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Nr. trombocite (x10<sup>3<\/sup>\/\u03bcL)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">De asemenea, analizorul automat calculeaz\u0103 <strong>l\u0103rgimea distributiei trombocitare <\/strong>(PDW) asem\u0103n\u0103tor cu calcularea l\u0103rgimii distributiei eritrocitare<sup>9<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong> \u2013\u00a0 VTM = 7.4-13 fL sau \u03bcm<sup>3<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">PDW = 8-16.5 coeficient de variatie (CV) a volumului trombocitar<sup>9<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong> \u2013 VTM poate fi utilizat impreun\u0103 cu PDW pentru distingerea conditiilor asociate cu productie scazut\u0103 de trombocite de cele asociate cu distructie plachetar\u0103 crescut\u0103.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">VTM crescut<\/span>:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In general VTM variaz\u0103 invers proportional cu num\u0103rul de trombocite, cu volume plachetare mai mari observate la pacientii trombocitopenici la care trombocitele sunt sc\u0103zute datorit\u0103 <em>distructiei periferice<\/em> si unui turn-over plachetar crescut (ca in purpura trombocitopenic\u0103 idiopatic\u0103)<sup>16<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">VTM este caracteristic crescut in <em>hipertiroidism<\/em> \u015fi in <em>bolile mieloproliferative<\/em> <sup>4;16<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In trombocitopoieza ineficient\u0103 asociat\u0103 cu hematopoieza megaloblastic\u0103 din <em>deficitul de vitamina B12 \u015fi\/sau acid folic<\/em> trombocitele circulante sunt anormal de mari.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">VTM poate fi crescut dup\u0103 <em>splenectomie<\/em>; este crescut in <em>pre-eclampsie<\/em>, la <em>fum\u0103torii aterosclerotici<\/em> (cresterea VTM la fum\u0103tori a fost propus\u0103 ca factor de risc pentru ateroscleroz\u0103)<sup>4<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Plachete mari sunt prezente in faza de recuperare dup\u0103 trombocitopenia indus\u0103 de <em>alcool<\/em><em><sup>4<\/sup><\/em>. Exist\u0103 cateva forme de trombocitopenie ereditar\u0103 caracterizate prin prezenta de trombocite gigante (VTM = 16-30 fL): <em>sindromul Bernard-Soulier<\/em> \u0438 <em>macrotrombocitopeniile ereditare cu transmitere autosomal dominant\u0103<\/em> (sindroamele Fechtner, Sebastian, May-Hegglin si Epstein)<sup>16;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In trombocitoz\u0103, VTM este de obicei crescut in bolile mieloproliferative (asociat cu morfologie anormal\u0103) \u015fi normal in trombocitozele reactive (infectii, tumori, boli inflamatorii etc.)<sup>13<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">VTM sc\u0103zut:<\/span><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Num\u0103rul de trombocite \u015fi VTM sunt de obicei sc\u0103zute in conditiile asociate cu <em>alterarea productiei de trombocite<\/em>: hipoplazia megakariocitara, anemia aplastic\u0103, chimioterapie, de asemenea in trombocitopenia septic\u0103<sup>4;16;17<\/sup>. Odat\u0103 cu ameliorarea tabloului clinic \u015fi refacerea dup\u0103 chimioterapie, VTM creste inaintea cresterii num\u0103rului de trombocite.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Pacientii cu <em>hipersplenism<\/em> au trombocite mai mici decat cei cu PTI, astfel m\u0103rimea trombocitelor poate servi ca mijloc pentru diferentierea intre trombocitopenia cauzat\u0103 de distructia imunologic\u0103 a plachetelor fat\u0103 de sindroamele cu splenomegalie<sup>4;16<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Prezenta de <em>fragmente trombocitare<\/em> (de ex. in leucemie) se poate asocia cu VTM sc\u0103zut<sup>4<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Dintre trombocitopeniile ereditare <em>sindromul Wiskott-Aldrich<\/em> \u0438 <em>trombocitopenia X-linkat\u0103<\/em> se asociaz\u0103 cu microcitoza trombocitar\u0103 (VTM ~jum\u0103tate fat\u0103 de valorile normale)<sup>10;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Exist\u0103 dovezi c\u0103 VTM se coreleaz\u0103 cu tendinta de sangerare la pacientii trombocitopenici: la VTM &gt;6.4 fL scade semnificativ frecventa sangerarilor; astfel VTM ar putea fi util in aprecierea oportunit\u0103tii administr\u0103rii de transfuzii de trombocite<sup>4<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Plachetele tind s\u0103 se m\u0103reasca in primele dou\u0103 ore in EDTA, micsorandu-se din nou o dat\u0103 cu prelungirea stoc\u0103rii probei, f\u0103cand dificil\u0103 standardizarea m\u0103sur\u0103torilor. De aceea interpretarea VTM \u015fi PDW trebuie facut\u0103 cu precautie<sup>16<\/sup>. VTM \u015fi PDW pot avea valori false dac\u0103 num\u0103rul de Tr este &lt;10000\/\u00b5L<sup>4<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Num\u0103rul de\u00a0leucocite\u00a0(num\u0103rul de celule albe) \u015fi formula<\/strong>\u00a0<strong>leucocitar\u0103 <\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Leucocitele se impart in dou\u0103 grupe principale: granulocite \u015fi a-\/non-granulocite. Granulocitele sunt denumite astfel datorit\u0103 prezentei in citoplasm\u0103 de granulatii distincte\u00a0\u015fi se identific\u0103 trei tipuri de granulocite in functie de afinit\u0103tile de colorare pe frotiul de sange colorat Wright: neutrofile, eozinofile\u00a0\u015fi bazofile. De asemenea, aceste celule sunt denumite\u00a0\u015fi leucocite polimorfonucleare datorit\u0103 nucleului multilobulat. Nongranulocitele care constau din limfocite\u00a0\u015fi monocite nu contin in general granulatii citoplasmatice distincte\u00a0\u015fi au nucleul nonlobulat, fiind denumite\u00a0\u015fi leucocite mononucleare<sup>2;4;6;8;12;16;18-20<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Indicatii<\/em><\/strong> \u2013 evaluarea infectiilor, inflamatiilor, necrozelor tisulare, intoxicatiilor, alergiilor, bolilor mieloproliferative \u015fi limfoproliferative acute\u00a0\u015fi cronice, tumorilor maligne, depresiei medulare (iradiere, medicamente citotoxice, imunosupresoare, antitiroidiene etc.)<sup>6;8;12<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda de determinare<\/em><\/strong> \u2013 leucocitele sunt determinate de analizorul automat (dup\u0103 ce hematiile sunt lizate, iar leucocitele sunt colorate cu o substant\u0103 fluorescent\u0103 cu afinitate pentru acizii nucleici) prin metoda de citometrie in flux cu fluorescenta utilizand LASER semiconductor. De asemenea, sunt efectuate dou\u0103 scatergrame bidimensionale. In scatergrama 4 DIFF axa x reprezint\u0103 intensitatea luminii dispersate lateral (respectiv complexitatea intern\u0103 a celulelor), iar axa y intensitatea fluorescentei laterale (respectiv continutul de acizi nucleici), sunt proiectate cele cinci clase leucocitare \u015fi grupul de umbre eritrocitare, precum\u00a0\u015fi anumite semnale de avertizare. In scatergrama WBC\/BASO axa x reprezint\u0103 intensitatea luminii dispersate lateral, iar axa y intensitatea luminii dispersate frontal (respectiv m\u0103rimea celulelor)\u00a0\u015fi sunt proiectate trei grupuri, respectiv grupul de umbre eritrocitare, grupul de\u00a0 bazofile\u00a0\u015fi grupul de alte leucocite<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong> \u2013 la adult = 4000-10000\/\u00b5L sau 4-10\u00d710<sup>9<\/sup>\/L<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u2013 la copii valori mai mari, diferite in functie de varst\u0103 <em>(vezi anexa7.1.1<\/em>).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Variatii fiziologice ale leucocitelor<\/span><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">cresterea \u015fi dezvoltarea: la nou-n\u0103scuti \u015fi copii num\u0103rul de leucocite este crescut, cu sc\u0103derea treptat\u0103 a valorilor, cu atingerea valorilor de la adult intre 18-21 ani<\/span><\/li>\n<li><span style=\"font-size: medium;\">variatii rasiale: la negrii din Africa num\u0103rul de neutrofile \u015fi monocite este mai mic, iar num\u0103rul de eozinofile mai mare<\/span><\/li>\n<li><span style=\"font-size: medium;\">fluctuatii diurne \u015fi de la o zi la alta: influentate de lumina; de asemenea activitatea obi\u015fnuit\u0103 determin\u0103 valori mai mari ale leucocitelor dup\u0103-amiaz\u0103, dar care tind s\u0103 r\u0103man\u0103 in limite normale<\/span><\/li>\n<li><span style=\"font-size: medium;\">variatii climatice \u015fi sezoniere: c\u0103ldura \u015fi radiatiile solare intense ar determina leucocitoz\u0103, iar rezidenta prelungit\u0103 in Antarctica determin\u0103 leucopenie; lumina artificial\u0103 \u015fi ultraviolet\u0103 determin\u0103 limfocitoza<\/span><\/li>\n<li><span style=\"font-size: medium;\">anoxia acut\u0103 determin\u0103 neutrofilie<\/span><\/li>\n<li><span style=\"font-size: medium;\">in primele zile de rezident\u0103 la altitudine crescut\u0103 apare leucocitoza asociat\u0103 cu limfopenie \u015fi eozinopenie, urmate de limfocitoz\u0103 \u015fi eozinofilie usoare<\/span><\/li>\n<li><span style=\"font-size: medium;\">exercitiile fizice intense determin\u0103 leucocitoza marcat\u0103, de obicei pe seama neutrofilelor segmentate (se datoreaz\u0103 trecerii neutrofilelor marginate in circulatie), dar poate fi prezenta \u015fi limfocitoza; normalizarea survine in mai putin de o or\u0103; gradul leucocitozei se coreleaz\u0103 cu intensitatea efortului fizic \u015fi nu cu durata sa<\/span><\/li>\n<li><span style=\"font-size: medium;\">crizele convulsive determin\u0103 cre\u015fterea num\u0103rului de leucocite<\/span><\/li>\n<li><span style=\"font-size: medium;\">injectiile cu epinefrin\u0103 determin\u0103 leucocitoz\u0103, in special neutrofilie<\/span><\/li>\n<li><span style=\"font-size: medium;\">atacurile de tahicardie paroxistic\u0103 pot determina leucocitoza<\/span><\/li>\n<li><span style=\"font-size: medium;\">durerea, greata, vars\u0103turile, anxietatea pot determina leucocitoza in absenta infectiei, prin redistribuirea celulelor marginate spre circulatie<\/span><\/li>\n<li><span style=\"font-size: medium;\">anestezia cu eter determina leucocitoza, iar narcoza cu compusi barbiturici de obicei scade numarul de leucocite;<\/span><\/li>\n<li><span style=\"font-size: medium;\">in\u00a0 perioada ovulatorie poate ap\u0103rea leucocitoza usoar\u0103 \u015fi eozinopenie<\/span><\/li>\n<li><span style=\"font-size: medium;\">in sarcin\u0103 apare leucocitoza usoar\u0103, iar neutrofilia se accentueaz\u0103 odat\u0103 cu apropierea termenului; de asemenea, in timpul travaliului apare neutrofilie uneori pronuntat\u0103, cu normalizarea valorilor dup\u0103 4-5 zile \u015fi asociat\u0103 cu eozinopenie<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Majoritatea variatiilor fiziologice se explic\u0103 prin stimularea cortexului adrenal. Administrarea de cortizon si hidrocortizon se asociaz\u0103 cu neutrofilie (datorat\u0103 probabil sc\u0103derii refluxului din sange \u015fi cre\u015fterii eliber\u0103rii medulare), urmat\u0103 de eozinopenie\u00a0\u015fi limfopenie<sup>18<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Leucocitoza<\/span>:<strong><em> L &gt;10000\/\u00b5L sau &gt;10\u00d710<sup>9<\/sup>\/L <\/em><\/strong><em>- <\/em>se datoreaz\u0103 de obicei unei cre\u015fteri a num\u0103rului de neutrofile sau limfocite; mai rar celelalte clase de leucocite determin\u0103 cre\u015fterea num\u0103rului absolut de leucocite. O cre\u015ftere proportional\u0103 a tuturor tipurilor de leucocite se datoreaz\u0103 hemoconcentratiei.<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">a. <em>Infectiile <\/em>reprezint\u0103 cauza major\u0103 de leucocitoz\u0103. O infectie acut\u0103 tipic\u0103 se caracterizeaz\u0103 printr-o faz\u0103 de atac neutrofilic\u0103, o faz\u0103 reactiv\u0103 monocitic\u0103 \u015fi o faz\u0103 de recuperare limfocitico-eozinofilic\u0103. In infectiile cronice poate persista oricare din aceste trei faze. Infectiile virale \u015fi unele infectii bacteriene (febra tifoid\u0103) nu urmeaz\u0103 in mod normal acest curs. Gradul leucocitozei depinde de severitatea infectiei, varsta \u015fi rezistenta pacientului, precum \u015fi de rezerva medular\u0103.<\/span><\/li>\n<li><span style=\"font-size: medium;\">b. <em>Alte cauze de leucocitoz\u0103:<\/em><\/span>\n<ul>\n<li><span style=\"font-size: medium;\">hemopatii maligne<\/span><\/li>\n<li><span style=\"font-size: medium;\">traumatisme\/injurii tisulare, de exemplu interventii chirurgicale, necroze tisulare<\/span><\/li>\n<li><span style=\"font-size: medium;\">tumori maligne (in special carcinomul bronsic)<\/span><\/li>\n<li><span style=\"font-size: medium;\">toxine, uremie, eclampsie, coma, tireotoxicoza<\/span><\/li>\n<li><span style=\"font-size: medium;\">medicamente: cloroform, chinina, factori de cre\u015ftere etc.<\/span><\/li>\n<li><span style=\"font-size: medium;\">hemoliza acut\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">hemoragie acut\u0103<\/span><\/li>\n<li><span style=\"font-size: medium;\">postsplenectomie<sup>18<\/sup><\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. <span style=\"text-decoration: underline;\">Leucopenie<\/span>:<strong><em> &lt;4000\/\u00b5L sau &lt;4\u00d710<sup>9<\/sup>\/L <\/em><\/strong>(valorile cuprinse intre 2500-4000\/\u00b5L sunt considerate borderline, in timp ce valorile &lt;2500\/\u00b5L sunt cert anormale)\u00a0 se poate datora urm\u0103toarelor cauze:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">infectii virale, unele infectii bacteriene, infectii bacteriene severe<\/span><\/li>\n<li><span style=\"font-size: medium;\">hipersplenism<\/span><\/li>\n<li><span style=\"font-size: medium;\">depresie medular\u0103 produs\u0103 de intoxicatie cu metale grele, benzen, radiatii ionizante, medicamente: chimioterapice, barbiturice, antibiotice, antihistaminice, anticonvulsivante, antitiroidiene, arsenic, diuretice, analgezice si antiinflamatorii<\/span><\/li>\n<li><span style=\"font-size: medium;\">boli medulare primitive: leucemie (aleucemica), anemie megaloblastic\u0103, sindroame mielodisplazice, anemie aplastic\u0103, boli congenitale (anemia Fanconi, discheratoza congenital\u0103)<\/span><\/li>\n<li><span style=\"font-size: medium;\">boli medulare secundare: granuloame, metastaze<sup>18<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. Num\u0103r fals crescut de leucocite: prezenta de <em>eritrocite rezistente la liza<\/em> (la nou-n\u0103scuti, reticulocitoza), prezenta de <em>eritroblasti<\/em> circulanti in num\u0103r mare, <em>trombocitele gigante<\/em> (pot fi num\u0103rate ca leucocite), prezenta de <em>crioglobuline<\/em> (la temperatura camerei se formeaz\u0103 cristale proteice care sunt num\u0103rate ca leucocite; dispar dup\u0103 inc\u0103lzirea probei la 37\u00b0C), <em>paraproteinemia<\/em>, prezenta de <em>aglutinine la rece<\/em>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. Num\u0103r fals sc\u0103zut de leucocite: prezenta de <em>leucocite alterate<\/em> (chimioterapie, sepsis) \u2013 nu sunt incluse in num\u0103r\u0103toare<sup>4;6;8;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #ff0000; font-size: medium;\"><strong><em>Valori critice<\/em><\/strong> \u2013 num\u0103r de leucocite <strong>&lt;500\/\u00b5L<\/strong>, respectiv <strong>&gt;30000\/\u00b5L<\/strong><sup>6<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><span style=\"text-decoration: underline;\">Formula leucocitar\u0103<\/span><\/strong> const\u0103 in diferentierea num\u0103rului total de leucocite circulante in cele cinci tipuri de leucocite, exprimate procentual \u015fi respectiv in num\u0103r absolut, fiecare dintre acestea indeplinind o functie specific\u0103. Actualmente este de preferat raportarea fiec\u0103rui tip de leucocite in valori absolute. Formula leucocitar\u0103 este efectuat\u0103 automat de c\u0103tre analizor. Exist\u0103 anumite situatii ins\u0103 in care este necesar\u0103 efectuarea manual\u0103 a formulei leucocitare: num\u0103r de leucocite prea mic\/prea mare, prezenta de celule anormale semnalizat\u0103 de analizor prin anumite mesaje de avertizare\/chiar esecul analizorului de a indica formula leucocitar\u0103. In aceste cazuri se efectueaz\u0103 num\u0103r\u0103toarea microscopic\u0103: frotiu de sange venos (recoltat pe EDTA; heparina poate produce deform\u0103ri ale leucocitelor) sau frotiu de sange capilar<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Neutrofilele (granulocitele polimorfonucleare neutrofile) <\/strong>\u2013 cel mai numeros tip de leucocite, joac\u0103 un rol major in ap\u0103rarea antiinfectioas\u0103 primar\u0103 a organismului prin fagocitarea \u015fi digestia microorganismelor, iar activarea lor necorespunzatoare poate duce la lezarea tesuturilor normale ale organismului prin eliberarea de enzime \u015fi agenti piogeni. In momentul aparitiei infectiei sunt produsi agenti chemotactici care determin\u0103 migrarea neutrofilelor la locul infectiei \u015fi activarea functiilor defensive ale acestora, cu fagocitarea agentului respectiv, urmat\u0103 de eliberarea granulelor in vezicula de fagocitoz\u0103 \u015fi distrugerea agentului infectios. Acest efect este adesea asociat cu cresterea productiei \u015fi eliberarii neutrofilelor din m\u0103duva osoas\u0103.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Granulopoieza are loc la nivelul m\u0103duvei osoase, considerandu-se ca granulocitele neutrofile, eozinofile si bazofile urmeaz\u0103 acelasi model de proliferare, diferentiere, maturare si eliberare in sange. Mieloblastii, promielocitele si mielocitele reprezint\u0103 compartimentul mitotic, celulele fiind capabile de replicare, iar metamielocitele, neutrofilele nesegmentate si neutrofilele segmentate reprezint\u0103 compartimentul postmitotic\/de diferentiere. In afara m\u0103duvei osoase, granulocitele neutrofile se g\u0103sesc in tesuturi, circulante la nivelul vaselor de sange si marginate care ader\u0103 la endoteliul vascular. Cresterea neutrofilelor circulante se datoreaz\u0103 fie eliber\u0103rii din m\u0103duva osoas\u0103, fie mobiliz\u0103rii neutrofilelor marginate. In cazul unei stimul\u0103ri puternice metamielocitele si mielocitele pot ajunge in sangele periferic<sup>18<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referint\u0103<\/em><\/strong>: \u2013\u00a0 la adult = 2000-8000\/\u00b5L sau 2-8\u00d710<sup>9<\/sup>\/L; 45-80% din leucocite<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u2013\u00a0 la copii valori mai mici in functie de varst\u0103<sup>9<\/sup> (<em>vezi anexa 7.1.1<\/em>)<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinic\u0103<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Neutrofilia<\/span>:<strong><em> &gt;8000\/\u00b5L sau 8\u00d710<sup>9<\/sup>\/L:<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\"><em>Pseudoneutrofilia<\/em> (cresterea numarului de neutrofile circulante pe seama neutrofilelor marginate): efort fizic intens, stres (plansul la copii), travaliu, menstruatie<\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectii bacteriene acute localizate \u015fi generalizate: neutrofilie pana la 15000-20000\/\u00b5L, foarte rar chiar pana la 50000\/\u00b5L; pot aparea granulatii toxice \u015fi devierea la stanga a formulei leucocitare, cu cre\u015fterea procentului de neutrofile nesegmentate (normal 1-4% din neutrofile), iar in cazul unui stimul puternic cu eliberarea de precursori medulari (metamielocite, mielocite). In infectii foarte severe poate aparea deviere la stanga degenerativa cu cresterea formelor imature fara leucocitoza (prognostic nefavorabil) sau reactie leucemoida (leucocite &gt;25000\/\u00b5L, devierea formulei leucocitare, uneori pana la mieloblast)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectii virale, fungice \u015fi parazitare: de obicei, neutrofilia este u\u015foara \u015fi este prezenta doar in faza initiala<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sepsis neonatal<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli inflamatorii cronice: vasculite, artrita reumatoida, bronsita, colita, dermatita, pielonefrita, pancreatita<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli metabolice: coma diabetica, coma uremica, coma hepatica, atacul acut de guta, eclampsia, tireotoxicoza<\/span><\/li>\n<li><span style=\"font-size: medium;\">Necroza tisulara: arsuri, infarct miocardic<\/span><\/li>\n<li><span style=\"font-size: medium;\">Toxice \u015fi medicamente: corticosteroizi, plumb, mercur, monoxid de carbon, digitala, veninuri<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hemoragia acuta (neutrofilie pana la 25000\/\u00b5L in a 3<sup>a<\/sup>-a 5<sup>a<\/sup> zi), proceduri chirurgicale majore, anemia hemolitica, postsplenectomie<\/span><\/li>\n<li><span style=\"font-size: medium;\">Tumori maligne, in special carcinoame (gastrointestinal, pulmonar): neutrofilia apare ca urmare a reactiei inflamatorii, necrozei tumorale, producerii de factori de crestere granulopoietici de catre tumora<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli mieloproliferative cronice (leucemia mieloida cronica, policitemia vera, trombocitemia esentiala, metaplazia mieloida cu mielofibroza)<em><sup>4<\/sup><\/em><sup>,<\/sup><sup>6;8;18;19<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Neutropenia<\/span>: se clasifica in u\u015foara (1000-1500\/\u00b5L), moderata (500-1000\/\u00b5L) \u015fi severa (&lt;500\/\u00b5L); agranulocitoza reprezinta o forma severa de neutropenie cu absenta totala a neutrofilelor circulante. Neutropenia severa se asociaza cu risc crescut de infectii cu localizare orala (ulcere, periodontita), cutaneo-mucoasa (piele, perirectal, genital), iar in neutropenia prelungita infectii sistemice (pulmonare, gastrointestinale, hematogene). Cauze de neutropenie:<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>\u00a0<\/em><\/strong><em>A.<\/em> <em>Pseudoneutropenia<\/em>: efectuarea hemogramei dupa un timp indelungat de la recoltare, prezenta paraproteinemiei care produce aglutinarea neutrofilelor, marginarea neutrofilelor.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>\u00a0<\/em><em>B.<\/em> <em>Neutropenia dobandita<\/em>:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Infectii bacteriene severe, septicemie in special cu bacterii Gram negative; infectii virale: neutropenia survine in primele 1-2 zile \u015fi persista 3-7 zile, de obicei fara semnificatie clinica; neutropenie prelungita poate aparea in infectii cu virusul hepatitic B, virusul Epstein-Barr, HIV; infectii cu protozoare (malarie), fungi, rickettsii.<\/span><\/li>\n<li><span style=\"font-size: medium;\">Substante chimice, toxice \u015fi medicamente:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">Neutropenie indusa imun: aminopirina, penicilina, antitiroidiene, aur, quinidina.<\/span><\/li>\n<li><span style=\"font-size: medium;\">Inhibitia granulopoiezei dependenta de doza: antibiotice \u03b2-lactamice, carbamazepina, acid valproic.<\/span><\/li>\n<li><span style=\"font-size: medium;\">Lezarea directa a micromediului medular sau a precursorilor mieloizi de catre medicament sau metabolitii acestuia.<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Medicamente care pot produce neutropenie:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">Metale grele: aur, arseniu, mercur<\/span><\/li>\n<li><span style=\"font-size: medium;\">Analgezice si antiinflamatorii: aminopirina, fenilbutazona, indometacin, ibuprofen, acid acetilsalicilic, barbiturice, mesalazina, quinina<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antipsihotice si antidepresive: fenotiazine, imipramin, desipramin, diazepam, clordiazepoxid, meprobamat, haloperidol<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anticonvulsivante: acid valproic, fenitoin, etosuximid, carbamazepin, lamotrigin<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antitiroidiene: tiouracil, propiltiouracil, metimazol, carbimazol, perclorat de potasiu, tiocianat<\/span><\/li>\n<li><span style=\"font-size: medium;\">Medicamente cardiovasculare: procainamida, captopril, propranolol, hidralazina, metildopa, diazoxid, nifedipin, propafenona, ticlopidina, enalapril, amiodarona, quinidina<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antihistaminice: cimetidina, ranitidina, famotidina<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antimicrobiene: peniciline, cefalosporine, vancomicina, cloramfenicol, gentamicina, clindamicina, doxiciclina, flucitozina, nitrofurantoin, griseofulvin, metronidazol, rifampicina, izoniazida, streptomicina, mebendazol, pirimetamina, levamisol, sulfonamide, etambutol, ciprofloxacin, trimetoprim, imipenem<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antimalarice: clorochin, hidroxiclorochin, quinacrin, dapsona<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antivirale: zidovudina, aciclovir, ganciclovir, terbinafin<\/span><\/li>\n<li><span style=\"font-size: medium;\">Antidiabetice: clorpropamid, tolbutamid<\/span><\/li>\n<li><span style=\"font-size: medium;\">Diuretice: acid etacrinic, acetazolamida, tiazide, spironolactona<\/span><\/li>\n<li><span style=\"font-size: medium;\">Diverse: alopurinol, colchicina, bezafibrat, tamoxifen, penicilamina, acid retinoic, metoclopramid, Rauwolfia, etanol, imunoglobuline intravenoase, omeprazol, levodopa<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Neutropenia nutritionala: casexie, stari debilitante, anorexie nervoasa, deficit de vitamina B12 si folat, deficit de cupru<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia imuna (prezenta de anticorpi anti-neutrofile)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia autoimuna primara (80% din cazuri apar la copii &lt;1an; neutropenia autoimuna cronica idiopatica) sau secundara (lupus eritematos sistemic, granulomatoza Wegener, artrita reumatoida, hepatita cronica, limfocitoza T-\u03b3, transplant medular, transfuzii)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia isoimuna neonatala<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindromul Felty: artrita reumatoida, splenomegalie \u015fi neutropenie<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia asociata cu activarea complementului: expunerea sangelui la membrane artificiale (dializa, afereza, by-pass cardiopulmonar), anafilaxie. Are loc agregarea \u015fi aderarea neutrofilelor la endoteliul vascular, in special pulmonar<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hipersplenism<\/span><\/li>\n<li><span style=\"font-size: medium;\">Chimioterapia in cancer, tratamentul cu metotrexat in artrita reumatoida<\/span><\/li>\n<li><span style=\"font-size: medium;\">Radiatii ionizante<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli hematopoietice: leucemia (aleucemica), anemia aplastica.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>C. Neutropenia congenitala \u015fi cronica:<\/em><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Neutropenia congenitala severa (sindromul Kostmann)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia ciclica (oscilatii periodice ale numarului de neutrofile de la neutropenie severa &lt;200\/\u00b5L la niveluri aproape normale): ereditara sau dobandita<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia benigna cronica: familiala \u015fi nonfamiliala<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia idiopatica cronica severa<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia asociata cu defecte imune congenitale: agamaglobulinemia X-linkata, sindromul de hiper-IgM, dis-gamaglobulinemia tip I, deficienta de IgA, hipo-gamaglobulinemia familiala<\/span><\/li>\n<li><span style=\"font-size: medium;\">Disgeneza reticulara (neutropenie severa, limfopenie, agamaglobulinemie \u015fi absenta imunitatii mediate celular)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Neutropenia asociata cu anomalii fenotipice: sindromul Shwachman, hipoplazia cartilaj-par, diskeratoza congenitala, sindromul Barth, sindromul Ch\u00e9diak-Higashi<\/span><\/li>\n<li><span style=\"font-size: medium;\">Mielokathexis<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindromul leucocitelor \u201clenese\u201d<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli metabolice: glicogenoza tip Ib, metilmalonic acidemia<sup>1<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong> \u2013 vezi variatii fiziologice ale leucocitelor, pseudoneutrofilia \u015fi pseudoneutropenia.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #ff0000; font-size: medium;\"><strong><em>Valori critice<\/em><\/strong> \u2013 numar de neutrofile <strong>&lt;200\/\u00b5L<\/strong> sau agranulocitoza \u2013 risc de infectii sistemice fatale.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Limfocitele <\/strong>\u2013 reprezinta o populatie celulara heterogena care difera in functie de origine, durata de viata, localizare la nivelul organelor limfoide \u015fi functie. De\u015fi unele caracteristici morfologice ca: marimea, granularitatea, raportul nucleo-citoplasmatic diferentiaza populatiile limfocitare una de cealalta, ele nu ofera indicii privind tipul \u015fi functia lor. Majoritatea limfocitelor din sange sunt mici, de\u015fi sunt comune \u015fi forme mai mari, cum ar fi limfocitele mari granulare care contin granulatii azurofile in citoplasma.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">65-80% din limfocite sunt celule T, 8-15% sunt celule B, iar ~10% sunt celule natural killer (NK) (celulele NK sunt morfologic distincte, unele dintre acestea fiind identice cu limfocitele mari granulare). Numai 2% din limfocite sunt prezente in sange. Limfopoieza are loc la nivelul organelor limfoide. Organele limfoide primare sunt maduva osoasa \u015fi timusul, unde are loc diferentierea antigen-independenta a limfocitelor din precursorii imaturi (limfocitele B se matureaza in maduva, iar limfocitele T in timus unde migreaza de la nivel medular). Dupa acest stadiu precoce de diferentiere, limfocitele imunocompetente sunt eliberate \u015fi se localizeaza in arii specifice din organele limfoide secundare: splina, ganglionii limfatici, placile Peyer de la nivelul intestinului \u015fi inelul Waldeyer, unde are loc stadiul final, antigen-dependent al diferentierii limfocitare \u015fi distribuirea de celule efectoare complet diferentiate a produ\u015filor acestora spre alte zone ale organismului.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Plasmocitele reprezinta celule B complet diferentiate, cu citoplasma abundenta, intens bazofila, uneori granulara \u015fi nucleu excentric, rotund-ovalar, cu cromatina densa cu aspect de \u201cspite de roata\u201d. Plasmocitele nu sunt prezente in mod normal in sange. Frecvent sunt intalnite celule intermediare (limfoplasmocite), ca in infectiile virale, inclusiv mononucleoza infectioasa sau in bolile imunologice cu hipergamaglobulinemie.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Celulele B controleaza raspunsul imun umoral mediat de anticorpi specifici antigenului ofensator. Celulele B cu memorie au durata lunga de viata \u015fi nu produc anticorpi pana in momentul restimularii antigenice, cand raspund la doze mult mai mici de antigen, prolifereaza clonal \u015fi produc o cantitate de anticorpi de 7-10 ori mai mare decat celule B neexperimentate antigenic.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Celulele T sunt implicate in raspunsul imun mediat celular \u015fi includ celulele T helper CD4<sup>+<\/sup>, celulele T supresor CD8<sup>+<\/sup> \u015fi celulele T citotoxice<sup>6;15;19<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referinta<\/em><\/strong> \u2013 adult: 1000-4000\/\u00b5L sau 1-4\u00d710<sup>9<\/sup>\/L; 20-55% din leucocite;<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u2013 la copii valori mai mari in functie de varsta<sup>9<\/sup> <em>(vezi anexa7.1.1)<\/em>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinica<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Limfocitoza:<\/span><strong><em> &gt;4000\/\u00b5L:<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>\u00a0<\/em><\/strong><em>A. Cauze benigne:<\/em><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Infectii virale<\/span><\/li>\n<li><span style=\"font-size: medium;\">Limfocitoza infectioasa (apare in special la copii)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Mononucleoza infectioasa: produsa de virusul Epstein-Barr, afecteaza in special adolescentii \u015fi adultii tineri, produce un tablou hematologic caracteristic cu limfo-monocitoza \u015fi prezenta pe frotiul de sange de limfocite atipice, activate (celulele Downey)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Alte infectii virale: infectii virale ale tractului respirator superior, infectii cu citomegalovirus, rujeola, oreion, varicela, hepatita acuta virala, infectie acuta cu HIV<\/span><\/li>\n<li><span style=\"font-size: medium;\">Alte infectii: infectii cronice (tuberculoza, sifilis), tuse convulsiva, toxoplasmoza, febra tifoida, bruceloza<\/span><\/li>\n<li><span style=\"font-size: medium;\">Numarul de limfocite poate depa\u015fi 15000\/\u00b5L in limfocitoza infectioasa, mononucleoza infectioasa, tusea convulsiva<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala Crohn, colita ulcerativa<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala Addison<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala serului, hipersensibitate medicamentoasa<\/span><\/li>\n<li><span style=\"font-size: medium;\">Vasculite<\/span><\/li>\n<li><span style=\"font-size: medium;\">Limfocitoza policlonala persistenta (conditie benigna rara, care afecteaza tipic femei\u00a0 fumatoare de varsta mijlocie, cu tendinta familiala, cu prezenta de limfocite binucleate cu citoplasma abundenta)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindromul de splenomegalie hiperreactiva din malarie<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>B. Cauze maligne:<\/em><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Cu celula B: leucemia limfocitara cronica, leucemia prolimfocitara cu celula B, leucemia cu celule paroase, faza leucemica din limfoamele nonhodgkin, macroglobulinemia Waldenstr\u00f6m<\/span><\/li>\n<li><span style=\"font-size: medium;\">Cu celula T: leucemia prolimfocitara cu celula T, leucemia\/limfomul cu celula T al adultului, sindromul S\u00e9zary, leucemia cu limfocite mari granulare<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Limfopenie<\/span>:<strong><em> &lt;1000\/\u00b5L:<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Imunodeficiente congenitale: sindroame de imunodeficienta combinata<\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectia HIV (scaderea selectiva a celulelor CD4<sup>+<\/sup>)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Chimioterapia (in special analogii nucleozidici: fludarabina, cladribina \u2013 produc scaderea marcata a celulelor CD4<sup>+<\/sup>, care poate persista ani de zile), radioterapia, medicatia imunosupresoare <\/span><\/li>\n<li><span style=\"font-size: medium;\">Lupus eritematos sistemic (sunt prezenti anticorpi anti-limfocitari care produc liza complement mediata a limfocitelor); boala mixta de tesut conjuctiv; dermatomiozita <\/span><\/li>\n<li><span style=\"font-size: medium;\">Tuberculoza avansata (miliara): scaderea marcata a celulelor CD4<sup>+<\/sup><\/span><\/li>\n<li><span style=\"font-size: medium;\">Virusul gripal (limfopenia apare tipic dupa rezolvarea infectiei) <\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala Hodgkin \u015fi alte malignitati <\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemia aplastica <\/span><\/li>\n<li><span style=\"font-size: medium;\">Administrarea de ACTH\/corticosteroizi; tumori hipofizare secretoare de ACTH; boala Cushing <\/span><\/li>\n<li><span style=\"font-size: medium;\">Pierderi crescute la nivelul tractului intestinal prin obstructia drenajului limfatic: tumori, boala Whipple, limfangiectazie intestinala; boli inflamatorii intestinale <\/span><\/li>\n<li><span style=\"font-size: medium;\">Uremia <\/span><\/li>\n<li><span style=\"font-size: medium;\">Diverse: sarcoidoza, insuficienta cardiaca congestiva, boli debilitante severe, mu\u015fcaturi de \u015farpe, arsuri, anestezie, proceduri chirurgicale, by-pass cardiopulmonar <\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. <span style=\"text-decoration: underline;\">Plasmocitele<\/span>: nu sunt prezente in mod normal in sange; sunt crescute in:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Mielom multiplu, leucemia cu plasmocite<\/span><\/li>\n<li><span style=\"font-size: medium;\">Cancer: ficat, san, prostata<\/span><\/li>\n<li><span style=\"font-size: medium;\">Ciroza<\/span><\/li>\n<li><span style=\"font-size: medium;\">Artrita reumatoida, lupusul eritematos sistemic<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala serului<\/span><\/li>\n<li><span style=\"font-size: medium;\">Unele infectii bacteriene, virale, parazitare<sup>4;6;8;15;19<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong> \u2013 vezi variatii fiziologice ale leucocitelor; efortul fizic, stresul, menstruatia pot produce limfocitoza.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>Interferente medicamentoase<\/em><em><sup>6<\/sup><\/em><em>:<\/em><\/span><\/p>\n<ul>\n<li><span style=\"font-size: medium;\"><strong>Cresc limfocitele:<\/strong> acid aminosalicilic, cefaclor, ceftazidim, clorambucil, clorpropamid, dexametazona, gabapentin, G-CSF, griseofulvin, haloperidol, levodopa, narcotice, ofloxacin, propiltiouracil, quazepam, spironolactona, triazolam, acid valproic.<\/span><\/li>\n<li><span style=\"font-size: medium;\"><strong>Scad limfocitele:<\/strong> alprazolam, asparaginaza, benzodiazepine, ceftriaxon, clorambucil, ciclosporina, dexametazona, eprosartan, fludarabina, acid folic, furosemid, hidrocortizon, ibuprofen, irinotecan, levofloxacin, litiu, mecloretamina, mirtazepina, muromonab-CD3, nelfinavir, ofloxacin, olsalazina, pamidronat, pentostatin, fenitoin, quazepam, terbinafina, tiamina, trastuzumab, triazolam<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori critice<\/em><\/strong> \u2013 numar de limfocite <strong>&lt;500\/\u00b5L<\/strong> cre\u015fte riscul de infectii, in special virale<sup>6<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Numar de celule CD4<sup>+<\/sup> sever scazut este cel mai bun indicator unic de infectii oportuniste<sup>18<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Monocitele<\/strong> \u2013 sunt cele mai mari celule din sange; fac parte din sistemul fagocitic mononuclear\/reticuloendotelial compus din monocite, macrofage \u015fi precursorii lor medulari. Monocitele sunt eliberate in sange \u015fi, dupa un scurt timp in circulatie, migreaza in diferite tesuturi, intamplator sau specific, ca raspuns la diferiti factori chemotactici. In tesuturi, ca raspuns la diferiti stimuli solubili, ele se diferentiaza in macrofage tisulare, cu calitati morfologice si functionale caracteristice, proces care a fost denumit activare\u00a0\u015fi care este reversibil (\u201cdezactivare\u201d). Celulele sistemului fagocitic mononuclear sunt foarte primitive filogenetic, nici un animal neputand trai fara ele. Indeplinesc o varietate larga de functii importante in organism, incluzand indepartarea particulelor straine\u00a0\u015fi celulelor senescente, moarte sau alterate, reglarea functiilor altor celule, procesarea\u00a0\u015fi prezentarea de antigene in reactiile imune, participarea in diferite reactii inflamatorii, distrugerea bacteriilor\u00a0\u015fi celulelor tumorale. Monocitele\u00a0\u015fi macrofagele produc numerosi factori bioactivi: enzime, factori ai complementului, factori de coagulare, specii reactive de oxigen\u00a0\u015fi azot, factori angiogenetici, proteine de legare (transferina, transcobalamina II, fibronectina, apolipoproteina E), lipide bioactive (derivati ai acidului arahidonic), factori chemotactici, citokine\u00a0\u015fi factori de cre\u015ftere (IFN \u03b1\u00a0\u015fi \u03b3, IL 1,3,6,8,10,12, FGF, PDGF, TNF, M-CSF) <sup>1;6;16<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referinta<\/em><\/strong> \u2013 0-1000\/\u00b5L sau 0-1\u00d710<sup>9<\/sup>\/L; 0-15% din leucocite<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinica<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Monocitoza<\/span>:<strong><em> &gt;1000\/\u00b5L:<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Cele mai frecvente cauze sunt infectiile bacteriene, tuberculoza, endocardita bacteriana subacuta, sifilisul, bruceloza<\/span><\/li>\n<li><span style=\"font-size: medium;\">Leucemia mielomonocitara cronica, leucemia monoblastica acuta, boli mieloproliferative cronice<\/span><\/li>\n<li><span style=\"font-size: medium;\">Carcinoame: stomac, san, ovar<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala Hodgkin, limfoame<\/span><\/li>\n<li><span style=\"font-size: medium;\">Recuperarea dupa neutropenie, chimioterapie, transplant medular (semn favorabil)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Tezaurismoze (boala Gaucher)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli parazitare (malarie, Kala-azar, tripanosomiaza), rickettsioze, infectii micotice<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli gastrointestinale: colita ulcerativa, enterita regionala, sprue, ciroza hepatica<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli de colagen, sarcoidoza<\/span><\/li>\n<li><span style=\"font-size: medium;\">Postchirurgical, postsplenectomie<\/span><\/li>\n<li><span style=\"font-size: medium;\">Reactii medicamentoase<\/span><\/li>\n<li><span style=\"font-size: medium;\">Intoxicatie cu tetracloretan<\/span><\/li>\n<li><span style=\"font-size: medium;\">Tratament cu factori de crestere granulo-monocitari<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Monocitopenie<\/span>:<strong><em> &lt;100\/\u00b5L <\/em><\/strong>(conditie extrem de rara)<strong><em>:<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Tratament cu prednison (tranzitoriu) <\/span><\/li>\n<li><span style=\"font-size: medium;\">Leucemia cu celule paroase <\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectii severe care determina si neutropenie <\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectie HIV <\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemie aplastica<sup>1;4;8;19<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente<\/em><\/strong> \u2013 vezi variatii fiziologice ale leucocitelor.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>Interferente medicamentoase:<\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Cresc monocitele:<\/strong> alprazolam, ampicilina, carbenicilina, clorpromazina, griseofulvin, haloperidol, lomefloxacin, metsuximid, penicilamina, piperacilina, prednison, propiltiouracil, quazepam.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Scad monocitele:<\/strong> alprazolam, triazolam<sup>6<\/sup>. <\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Eozinofilele (granulocitele eozinofile)<\/strong><sup>6;9;18<\/sup>\u2013 au fost initial descrise pentru granulatiile lor intracitoplasmatice caracteristice care manifesta afinitate crescuta pentru colorantii acizi, cum ar fi eozina, \u015fi care apar colorate ro\u015fu-stralucitor in microscopia optica. Eozinofilele sunt celule mobile, cu originea in maduva osoasa, urmand acela\u015fi model de proliferare, diferentiere, maturare \u015fi eliberare in sange ca \u015fi granulocitele neutrofile; nucleul lor este de obicei bilobat, dar sunt adesea observati \u015fi trei sau mai multi lobi.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">La indivizii sanatosi se gasesc in numar mic in sange, dar devin predominante in sange \u015fi tesuturi in asociere cu diferite boli alergice, parazitare sau boli maligne. Prezenta eozinofilelor in caile respiratorii \u015fi mucoasa intestinala, numarul cat \u015fi starea lor de activare, a fost asociata atat cu maifestarile IgE-dependente cat \u015fi IgE-independente ale bolilor alergice. Totusi, rolul imunologic \u015fi importanta eozinofilului in patogeneza astmului nu sunt pe deplin clarificate. Eozinofilele contin cel putin cinci tipuri diferite de granulatii intracitoplasmatice; granulatiile cristaloide contin cea mai mare parte a proteinelor cationice cu incarcatura mare, incluzand proteina bazica majora, peroxidaza, proteina cationica eozinofilica si neurotoxina derivata din eozinofil, implicate in alterarile tisulare observate in astm \u015fi alte boli alergice. Eozinofilia indusa de alergeni sau paraziti este dependenta de celula T \u015fi este mediata de citokine eliberate de limfocitele sensibilizate. Eozinofilul produce \u015fi stocheaza pana la 29 de mediatori cunoscuti, citokine, chemokine \u015fi factori de cre\u015ftere, importante in reactiile inflamatorii in care este implicata aceasta celula (produ\u015fi ai acidului arahidonic, interleukine 1\u03b1-6, 8, 9-13, 16, IFN\u03b3, TNF, TGF\u03b1, TGF\u03b21, NGF, PDGF-B,SCF, GM-CSF, eotaxina, MIP-1\u03b1, RANTES).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referinta<\/em><\/strong>: 0-700\/\u00b5L sau 0-0.7\u00d710<sup>9<\/sup>\/L (0-7% din leucocite); valori mai mici la copiii pana la 1 an<em> (vezi anexa 1).<\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em><strong>Semnificatie clinica<\/strong><\/em> <sup>4;6;8;9;18<\/sup><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>1. Eozinofilia &gt;700\/\u00b5L:<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Boli alergice:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">Astmul bronsic: exista o corelatie intre hiperreactivitatea bronsica \u015fi gradul eozinofiliei; biopsia bronsica identifica prezenta eozinofilelor in caile respiratorii; in astmul intrinsec\/nonatopic in care lipseste dependenta de un raspuns imun dependent de IgE, exista o cre\u015ftere similara a eozinofilelor in caile aeriene<\/span><\/li>\n<li><span style=\"font-size: medium;\">Dermatita atopica, urticaria, edemul angioneurotic, sensibilizarea la aspirina, alergii medicamentoase (trimetoprim-sulfametoxazol, penicilina, tetraciclina, nitrofurantoin), febra fanului<\/span><\/li>\n<li><span style=\"font-size: medium;\">Esofagita eozinofilica (posibil asociata cu alergie la alimente), gastroenterita eozinofilica, proctocolita eozinofilica (asociata cu alergia la laptele de vaca, de\u015fi poate aparea \u015fi la copii hraniti cu formule de soia sau alimentati la san).<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Asocierea dintre infiltrate pulmonare si eozinofilie apare in:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">Sindromul L\u00f6ffler (infiltrat eozinofilic pulmonar tranzitoriu) \u2013 se poate asocia cu infestarea cu specii de Ascaris<\/span><\/li>\n<li><span style=\"font-size: medium;\">Angeita alergica \u015fi granulomatoasa (sindromul Churg-Strauss \u2013 tablou astmatiform, eozinofilie \u015fi vasculita sistemica)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Vasculita de hipersensibilizare<\/span><\/li>\n<li><span style=\"font-size: medium;\">Aspergiloza bronho-pulmonara alergica (se caracterizeaza printr-un tablou de astm, test cutanat pozitiv la aspergilus \u015fi prezenta de anticorpi precipitanti anti-aspergilus)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Eozinofilia tropicala (infestare parazitara pulmonara: filariaza)<\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">In plus, reactiile medicamentoase, sindromul hipereozinofilic \u015fi infestatiile parazitare se pot asocia cu eozinofilie si infiltrate pulmonare<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Boli neoplazice:<\/span>\n<ul>\n<li><span style=\"font-size: medium;\">Sindromul hipereozinofilic idiopatic: rar, mai frecvent la barbati (B:F=9:1), eozinofilie pana la 50000\/\u00b5L, diferentiat de leucemia eozinofilica prin absenta blastilor, determina afectare organica multipla, alterare nervoasa centrala \u015fi deces de obicei prin disfunctie cardiaca<\/span><\/li>\n<li><span style=\"font-size: medium;\">Leucemia eozinofilica<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala Hodgkin si limfoamele maligne<\/span><\/li>\n<li><span style=\"font-size: medium;\">Bolile mieloproliferative cronice<\/span><\/li>\n<li><span style=\"font-size: medium;\">Carcinomul bronsic (prin productie excesiva de IL5)<\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"font-size: medium;\">Boli gastrointestinale: boala Crohn, colita ulcerativa<\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectia HIV: se poate datora infestatiilor parazitare intercurente, reactiei la trimetoprim-sulfametoxazol utilizat pentru tratamentul infectiei cu Pneumocystis carinii<\/span><\/li>\n<li><span style=\"font-size: medium;\">Infestari parazitare in special helmintice (trichineloza, chist hidatic, schistosomiaza, fascioloza, toxocaroza \u2013 \u201clarva migrans\u201d viscerala, cisticercoza, scabie), in special in timpul fazei de migrare tisulara<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli cutanate: pemfigus vulgaris, dermatita herpetiforma, eritem exsudativ multiform<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli infectioase (febra ro\u015fie), in convalescenta dupa alte infectii<\/span><\/li>\n<li><span style=\"font-size: medium;\">Eozinofilia familiala (rara)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Eozinofilie iatrogena: tratamentul bolilor maligne cu IL-2, administrarea de GM-CSF, rejetul alogrefei<\/span><\/li>\n<li><span style=\"font-size: medium;\">Sindromul eozinofilie-mialgie: produs de ingestia de L-triptofan, potential fatal (polineuropatie ascendenta Guillain-Barr\u00e9-like)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Rinita eozinofilica nonalergica<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\"><em>!Cele mai mari valori ale numarului de eozinofile (&gt;1500\/\u00b5L) apar in sindromul hipereozinofilic idiopatic, leucemia cu eozinofile, trichineloza si dermatita herpetiforma<\/em><em><sup>6;18<\/sup><\/em><em>.<\/em><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>2. Eozinopenia <\/em><\/strong>se datoreaza in general unei productii crescute de steroizi, care acompaniaza majoritatea conditiilor de stres \u015fi se asociaza cu:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">\u0421\u0438\u043d\u0434\u0440\u043e\u043c \u041a\u0443\u0448\u0438\u043d\u0433\u0430<\/span><\/li>\n<li><span style=\"font-size: medium;\">Medicamente: ACTH, corticosteroizi, epinefrina, tiroxina, prostaglandine<\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectii acute<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interferente <\/em><\/strong><em><sup>4;6;8<\/sup><\/em>: vezi variatii fiziologice ale leucocitelor.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. Ritmul circadian: numarul de eozinofile este minim dimineata \u015fi cre\u015fte de la pranz pana dupa miezul noptii<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. Conditiile de stres scad numarul de eozinofile<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>3. Interferente medicamentoase:<\/em><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\"><strong>Cresc eozinofilele:<\/strong> alopurinol, alprazolam, acid aminosalicilic, amoxicilina, amfotericina B, ampicilina, aztreonam, benazepril, captopril, carbamazepin, carbenicilina, cefoperazon, cefotaxim, ceftazidim, ceftriaxon, cefalexin, cloramfenicol, clorpromazina, ciprofloxacin, clindamicina, clofibrat, clonazepam, danazol, dapsona, desipramina, diazoxid, diclofenac, doxepin, doxorubicina, doxiciclina, enalapril, etosuximid, flucitozina, fluorouracil, flufenazina, furazolidon, famciclovir, gemfibrozil, gentamicina, haloperidol, vaccin anti-hepatita A, ibuprofen, imipenem, isoniazida, lamotrigin, lansoprazol, levodopa, acid mefenamic, mefenitoin, metsuximid, metisergid, moxalactam, naproxen, nitrofurantoin, nizatidina, norfloxacina, ofloxacina, penicilinamina, pentazocin, perfenazina, piperacilina, piroxicam, procarbazina, propafenona, ramipril, ranitidina, rifampicina spironolactona, streptomicina, sulfametoxazol, sulfasalazina, tetraciclina, tioridazina, ticarcilina, ticlopidina, tobramicina, triazolam, trifluoperazina, trimipramina, trovafloxacin, acid valproic, zalcitabina<sup>6<\/sup>.<\/span><\/li>\n<li><span style=\"font-size: medium;\"><strong>Scad eozinofilele:<\/strong> amitriptilina, aspirina, captopril, clozapin, corticotropin, desipramina, etosuximid, indometacin, nortriptilina, olsalazina, procainamida, rifampicina, sulfametoxazol, triazolam<sup>6<\/sup>.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong>Bazofilele (granulocitele bazofile)<\/strong> \u0438 <strong>mastocitele <\/strong>\u2013 sunt doua populatii de leucocite bazofile care prezinta multe asemanari, dar \u015fi unele diferente. Ambele tipuri de celule contin granulatii intracitoplasmatice care se coloreaza metacromatic cu coloranti bazici. De asemenea, ambele exprima pe suprafata lor o isoforma tetramerica (\u03b1\u03b2\u03b32) a receptorului cu afinitate mare pentru IgE. Cand acest receptor cu afinitate mare este legat de alergenul sensibilizant sau de anticorpii anti-IgE, atat bazofilele, cat \u015fi mastocitele sunt activate, fiind indusa sinteza \u015fi secretia de mediatori. Prin aceste mecanisme bazofilele \u015fi mastocitele sunt factori importanti in inflamatiile alergice \u015fi alte fenomene imune \u015fi inflamatorii.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Bazofilele sunt celule avand kinetica \u015fi istoria naturala a granulocitelor, care se matureaza in maduva, circula in sange \u015fi retin anumite trasaturi ultrastructurale caracteristice dupa migrarea in tesuturi in timpul proceselor inflamatorii \u015fi imunologice (hipersensibilitate cutanata bazofilica, astm). Nu exista evidente convingatoare ca bazofilele se metamorfozeaza in mastocite dupa migrarea in tesuturi.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Mastocitele se matureaza in mod obi\u015fnuit in afara maduvei osoase sau circulatiei \u2013 in general in tesutul conjunctiv \u015fi cavitatile seroase. Exista anumite conditii in care numarul de progenitori mastocitari din circulatie poate fi crescut.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Bazofilele \u015fi mastocitele difera semnificativ in ceea ce priveste fenotipul de suprafata, forma \u015fi structura nucleului; bazofilele au in general mai putine granule \u015fi o morfologie mai omogena decat mastocitele. Exista, de asemenea, diferente in ceea ce priveste mediatorii stocati \u015fi cei nou sintetizati dupa activare. Ambele celule contin histamina, PAF \u015fi metaboliti ai acidului arahidonic, considerate importante in patogeneza bolilor inflamatorii, cum ar fi astmul. O distinctie majora consta in proteinazele care sunt continute in cantitate abundenta in mastocite. Ambele celule produc citokine, spre exemplu bazofilele produc cantitati mari de IL-4 si IL-13, in timp ce repertoriul mastocitelor include un spectru larg de citokine, asociate cu fenotipurile Th1 si Th2 (cum ar fi TNF).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">De asemenea, rolul bazofilelor \u015fi mastocitelor in inflamatiile alergice difera in functie de stimulii care activeaza fiecare celula. Cateva populatii mastocitare raspund la unele neuropeptide, iar asocierea anatomica stransa dintre mastocite \u015fi nervi constituie evidenta componentei neurogenice-dependente de mastocite a reactiilor alergice.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Degranularea anafilactica survine dupa stimularea receptorului pentru IgE sau prin alti stimuli cum ar fi componente ale complementului. Degranularea anafilactica poate fi extensiva implicand majoritatea granulelor. Dar in numeroase reactii inflamatorii in care apare infiltrare mastocitara \u015fi bazofilica, cum ar fi hipersensibilitatea cutanata intarziata, poate aparea o degranulare\u00a0\u015fi secretie de mediatori mult mai putin exploziva (\u201cpiecemeal degranulation\u201d). Dupa degranulare, celule sunt capabile sa se refaca\u00a0\u015fi sa functioneze din nou<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referinta<\/em><\/strong> \u2013 bazofile = 0-200\/\u00b5L sau 0-0.2\u00d710<sup>9<\/sup>\/L (0-2% din leucocite)<sup>9<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Semnificatie clinica<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">1. <span style=\"text-decoration: underline;\">Bazofilia:<\/span><strong><em> &gt;200\/\u00b5L:<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Numarul de bazofile \u015fi precursori mastocitari este crescut in boli alergice: rinita alergica, polipoza nazala, sinuzita cronica, astm, dermatita atopica, alergii medicamentoase<\/span><\/li>\n<li><span style=\"font-size: medium;\">In leucemia megakarioblastica din sindromul Down (trisomia 21) exista diferentiere bazofilica (care poate include mastocitele) din progenitorii leucemici<\/span><\/li>\n<li><span style=\"font-size: medium;\">Leucemia mieloida cronica \u015fi alte sindroame mieloproliferative cronice (policitemia vera, metaplazia mieloida cu mielofibroza). Nivelul bazofiliei are valoare prognostica, iar criza bazofilica anunta faza blastica terminala din leucemia mieloida cronica. Hiperhistaminemia din leucemia mieloida cronica \u015fi celelalte sindroame mieloproliferative se coreleaza cu numarul \u015fi turn-overul bazofilelor (posibil \u015fi al mastocitelor)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Mastocitoza sistemica, urticaria pigmentosa (o forma pediatrica de proliferare mastocitara limitata, cu localizare cutanata) \u2013 numar crescut de bazofile \u015fi precursori mastocitari in sange<\/span><\/li>\n<li><span style=\"font-size: medium;\">Leucemie bazofilica<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boala Hodgkin<\/span><\/li>\n<li><span style=\"font-size: medium;\">Anemie hemolitica cronica, postsplenectomie<\/span><\/li>\n<li><span style=\"font-size: medium;\">Postradiatii ionizante<\/span><\/li>\n<li><span style=\"font-size: medium;\">Infectii: tuberculoza, varicela, gripa<\/span><\/li>\n<li><span style=\"font-size: medium;\">Injectarea de particule straine<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hipotiroidism<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">2. <span style=\"text-decoration: underline;\">Bazopenia<\/span>:<strong><em> &lt;20\/\u00b5L:<\/em><\/strong><\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Infectii in faza acuta<\/span><\/li>\n<li><span style=\"font-size: medium;\">Reactii de stres (sarcina, infarct miocardic)<\/span><\/li>\n<li><span style=\"font-size: medium;\">Dupa tratament prelungit cu steroizi, chimioterapie, iradiere<\/span><\/li>\n<li><span style=\"font-size: medium;\">Absenta ereditara a bazofilelor<\/span><\/li>\n<li><span style=\"font-size: medium;\">Febra reumatica acuta la copii<\/span><\/li>\n<li><span style=\"font-size: medium;\">Hipertiroidism<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">3. <span style=\"text-decoration: underline;\">Prezenta de precursori mastocitari in sange<\/span>:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">Urticarie, astm<\/span><\/li>\n<li><span style=\"font-size: medium;\">Soc anafilactic<\/span><\/li>\n<li><span style=\"font-size: medium;\">Mastocitoza sistemica, urticaria pigmentosa, leucemia cu mastocite<\/span><\/li>\n<li><span style=\"font-size: medium;\">Macroglobulinemie, limfoame cu invazie medulara<\/span><\/li>\n<li><span style=\"font-size: medium;\">Insuficienta corticosuprarenaliana<\/span><\/li>\n<li><span style=\"font-size: medium;\">Boli hepatice si renale cronice<\/span><\/li>\n<li><span style=\"font-size: medium;\">\u041e\u0441\u0442\u0435\u043e\u043f\u043e\u0440\u043e\u0437 <sup>4;6;8;19<\/sup><\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><em>Interferente medicamentoase<\/em>:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\"><strong>Cre\u015fteri ale bazofilelor<\/strong>: desipramina, paroxetin, tretinoin, triazolam<\/span><\/li>\n<li><span style=\"font-size: medium;\"><strong>Scaderi ale bazofilelor:<\/strong> procainamida, tiopental<sup>6<\/sup><\/span><\/li>\n<\/ul>\n<p><em>Anexa 7.1.1<\/em><\/p>\n<table class=\"wp-block-table w-100\" width=\"1017\">\n<tbody>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>\u0425<\/strong><strong>\u00e2rst\u0103<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>Nr. eritro-<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>cite<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>(x10<sup>6<\/sup>\/\u00b5L)<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>Hb<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>(g\/dL)<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>Ht<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>(%)<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>VEM<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>(fL)<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>HEM<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>(pg)<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>CHEM<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>(g\/dL)<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>Nr.<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>leuco-<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>cite<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>(x10<sup>3<\/sup>\/\u00b5L)<\/strong><\/span><\/td>\n<td style=\"width: 185px;\" colspan=\"3\"><span style=\"font-size: 10pt;\"><strong>Nr. neutrofile<\/strong><\/span><\/td>\n<td style=\"width: 58px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>Limfo-<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>cite<\/strong><\/span><\/td>\n<td style=\"width: 56px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>Mono-<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>cite<\/strong><\/span><\/td>\n<td style=\"width: 65px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>Eozino-<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>file<\/strong><\/span><\/td>\n<td style=\"width: 51px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>Bazo-file<\/strong><\/span><\/td>\n<td style=\"width: 96px;\" rowspan=\"4\"><span style=\"font-size: 10pt;\"><strong>Trombocite (x10<sup>3<\/sup>\/<\/strong><strong> \u00b5L)<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>Total<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>Nesegm.<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>Segm.<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>%<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>%<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>%<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>%<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>%<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>%<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>%<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>#<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>#<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>#<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>#<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>#<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>#<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>#<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>&lt;1 luna<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.9-5.9<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>13.4-19.8<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>41-65<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>85-120<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>30-37<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>28-35<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>5.0-20.0<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>20-40<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>20-35<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>35-65<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-15<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<td style=\"width: 96px;\" rowspan=\"32\"><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>\u00a0<\/strong><\/span><\/p>\n<p><span style=\"font-size: 10pt;\"><strong>150 -450<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.0-9.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-0.5<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.0-9.0<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>2.0-17.0<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.7<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.85<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.6<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>1 luna<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.3-5.3<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>10.7-17.1<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>33-55<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>85-110<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>29-36<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>28-35<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>5.0-20.0<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>20-40<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>20-35<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>40-70<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.0-9.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-0.5<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.0-9.0<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>2.0-17.0<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.85<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.6<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>2-3 luni<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.3-5.3<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>9.4-13.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>28-42<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>84-106<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>27-34<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>28-35<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6.0-17.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>15-50<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>15-40<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>40-70<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.0-8.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.0-7.5<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>4.0-13.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.6<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4-5 luni<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.5-5.1<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>10.3-14.1<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-44<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>76-97<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>25-32<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>29-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6.0-17.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>15-50<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>15-40<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>40-70<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.0-8.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.0-7.5<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>4.0-13.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.6<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6-8 luni<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.9-5.5<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>11.4-14.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>33-41<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>70-89<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>25-30<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6.0-17.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>15-50<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>15-40<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>40-70<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.0-8.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.5-7.5<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>4.0-13.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>9-11 luni<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.0-5.3<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>11.4-14.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>33-41<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>70-89<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>25-30<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6.0-17.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>15-50<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>15-40<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>40-65<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.0-8.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.5-7.5<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>4.0-10.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>1 an<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.1-5.3<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>11.3-14.1<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-40<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>70-89<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>22-30<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-38<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6.0-17.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>20-65<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>40-65<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-5<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.5-8.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.5-7.5<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>4.0-10.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>2-3 ani<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.7-4.9<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>11.0-14.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-42<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>73-89<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>25-31<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6.0-17.0<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>30-75<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>30-65<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>30-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.5-8.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.5-7.5<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>3.0-9.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4-5 ani<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.7-4.9<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>11.0-14.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-42<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>73-89<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>25-31<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>5.5-15.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>30-75<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>30-65<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>25-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.5-8.5<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.5-7.5<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>2.0-8.0<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>6-8 ani<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.8-4.9<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>11.5-14.5<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>33-41<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>75-89<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>25-31<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>5.0-14.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>30-75<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>30-65<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.5-8.0<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.5-7.0<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>1.5-7.0<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 58px;\" colspan=\"2\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>9-11 ani<\/strong><\/span><\/td>\n<td style=\"width: 60px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>3.9-5.1<\/strong><\/span><\/td>\n<td style=\"width: 55px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>12.0-15.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>34-43<\/strong><\/span><\/td>\n<td style=\"width: 46px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>76-90<\/strong><\/span><\/td>\n<td style=\"width: 47px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>26-32<\/strong><\/span><\/td>\n<td style=\"width: 57px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.5-13.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>35-75<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>35-65<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-15<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.8-8.0<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.8-7.0<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>1.5-6.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 32px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>12-14 ani<\/strong><\/span><\/td>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0411<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>4.1-5.2<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>12.0-16.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>35-45<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>77-94<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>26-32<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.5-13.5<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>40-75<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>40-65<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-15<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0415<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>3.8-5.0<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>11.5-15.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>34-44<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>76-95<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>26-32<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-36<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.8-8.0<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.8-7.0<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>1.5-6.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 32px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>15-17 ani<\/strong><\/span><\/td>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0411<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>4.2-5.6<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>11.7-16.6<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>37-48<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>79-95<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>27-32<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-36<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.5-13.0<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>40-75<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-10<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>40-65<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-15<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0415<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>3.9-5.1<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>11.7-15.3<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>34-44<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>78-98<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>26-34<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-36<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>1.8-8.0<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>1.8-7.0<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>1.5-6.5<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 32px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>18-44 ani<\/strong><\/span><\/td>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0411<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>4.3-5.7<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>13.2-17.3<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>39-49<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>80-99<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>27-34<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-37<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.0-10.0<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>45-80<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-4<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>45-76<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-15<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0415<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>3.8-5.1<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>11.7-15.5<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>35-45<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>81-100<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>27-34<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-36<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>2.0-8.0<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-0.4<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>2.0-7.6<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>1.0-4.0<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0.3-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0.05-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 32px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>45-64 ani<\/strong><\/span><\/td>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0411<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>4.2-5.6<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>13.1-17.2<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>39-50<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>81-101<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>27-35<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-36<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.0-10.0<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>45-80<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-4<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>45-76<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-15<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0415<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>3.8-5.3<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>11.7-16.0<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>35-47<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>81-101<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>27-34<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>31-36<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>2.0-8.0<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-0.4<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>2.0-7.6<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>1.0-4.0<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0.3-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0.05-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 32px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>65-74 ani<\/strong><\/span><\/td>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0411<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>3.8-5.8<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>12.6-17.4<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>37-51<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>81-103<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>27-34<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>31-36<\/strong><\/span><\/td>\n<td style=\"width: 59px;\" rowspan=\"2\"><span style=\"font-size: 10pt;\"><strong>4.0-10.0<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>45-80<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-4<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>45-76<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>20-55<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0-15<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0-7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-2<\/strong><\/span><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 20px;\"><span style=\"font-size: 10pt;\"><strong>\u0415<\/strong><\/span><\/td>\n<td style=\"width: 60px;\"><span style=\"font-size: 10pt;\"><strong>3.8-5.2<\/strong><\/span><\/td>\n<td style=\"width: 55px;\"><span style=\"font-size: 10pt;\"><strong>11.7-16.1<\/strong><\/span><\/td>\n<td style=\"width: 36px;\"><span style=\"font-size: 10pt;\"><strong>35-47<\/strong><\/span><\/td>\n<td style=\"width: 46px;\"><span style=\"font-size: 10pt;\"><strong>81-102<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>27-35<\/strong><\/span><\/td>\n<td style=\"width: 57px;\"><span style=\"font-size: 10pt;\"><strong>32-36<\/strong><\/span><\/td>\n<td style=\"width: 47px;\"><span style=\"font-size: 10pt;\"><strong>2.0-8.0<\/strong><\/span><\/td>\n<td style=\"width: 72px;\"><span style=\"font-size: 10pt;\"><strong>0-0.4<\/strong><\/span><\/td>\n<td style=\"width: 54px;\"><span style=\"font-size: 10pt;\"><strong>2.0-7.6<\/strong><\/span><\/td>\n<td style=\"width: 58px;\"><span style=\"font-size: 10pt;\"><strong>1.0-4.0<\/strong><\/span><\/td>\n<td style=\"width: 56px;\"><span style=\"font-size: 10pt;\"><strong>0.3-1.0<\/strong><\/span><\/td>\n<td style=\"width: 65px;\"><span style=\"font-size: 10pt;\"><strong>0.05-0.7<\/strong><\/span><\/td>\n<td style=\"width: 51px;\"><span style=\"font-size: 10pt;\"><strong>0-0.2<\/strong><\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify;\"><strong><span style=\"font-size: small;\">\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/span><\/strong><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">1. B Weinberg. Monunuclear Phagocytes. In Wintrobe\u2019s Clinical Hematology. Philadelphia ed. 2004, 349-377.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">2. Befus D, Denburg J. Basophilic Leukocytes: Mast Cells and Basophils. In Wintrobe\u2019s Clinical Hematology. Lippincott, Williams, and Wilkins, Philadelphia, 11 ed. ed. 2004, 336-345.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">3. Carmel L. Megaloblastic Anemias: Disorders of Impaired DNA Synthesis. In Wintrobe\u2019s Clinical Hematology. Lippincott, Williams, and Wilkins, Philadelphia, 11 ed. 2004, 1367-1413.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">4. DeMott W, Tilzer L. Hematology. In Laboratory Test Handbook. Hudson (Cleveland) ed. 1994, 517-617.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">5. Desai S. Complete Blood Count. In Clinicians\u2019s Guide to Laboratory Medicine. Hudson (Cleveland) ed. 2004, 13-18.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">6. Fischbach F. Blood Studies: Hematology and Coagulation; Appendix J: Effects of the Most Commonly Used Drugs on Frequently Ordered Laboratory Tests. In A Manual of Laboratory and Diagnostic Tests. Lippincott Williams &amp; Wilkins, Philadelphia, 8 ed. 2009, 67-110, 1227-1247.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">7. Glader B. Anemia: General Considerations. In Wintrobe\u2019s Clinical Hematology, Philadelphia. 2004, 948-975.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">8. J Wallach. Hematologic Diseases. In Interpretation of Diagnostic Tests. Philadelphia ed. 1996, 293-316.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">9. Laborator Synevo. Referintele specifice tehnologiei de lucru utilizate. 2010. Ref Type: Catalog<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">10. Lacy P, Becker A, Moqbel R. The Human Eosinophil. In Wintrobe\u2019s Clinical Hematology. Philadelphia, ed. 2004, 311-329.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">11. Levine S. Miscellaneous Causes of Thrombocytopenia. In Wintrobe\u2019s Clinical Hematology, Philadelphia. Philadelphia ed. 2004, 1565-1570.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">12. Levine S. Thrombocytopenia: Pathophysiology and Classification. In Wintrobe\u2019s Clinical Hematology. Philadelphia ed. 2004, 1529-1531.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">13. Levine S. Thrombocytosis. In Wintrobe\u2019s Clinical Hematology. Philadelphia ed. 2004, 1591-1597.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">14. Means R. Erythrocytosis. In Wintrobe\u2019s Clinical Hematology. Philadelphia ed. 2004, 1495-1505.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">15. Paraskevas F. Lymphocytes and Lymphatic Organs. In Wintrobe\u2019s Clinical Hematology. Philadelphia, ed. 2004, 409-433.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">16. Perkins S. Examination of the Blood and Bone Marrow. In Wintrobe\u2019s Clinical Hematology. Philadelphia, ed. 2004, 3-21.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">17. Rodgers G. Diagnostic Approach of the Bleeding Disorders. In Wintrobe\u2019s Clinical Hematology. Philadelphia ed. 2004, 1511-1526.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">18. Skubitz K. Neutrofilic Leukocytes. In Wintrobe\u2019s Clinical Hematology. Philadelphia ed. 2004, 268-303.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">19. Thomas L, Bartl R. Hematology. In Clinical Laboratory Diagnostics. 1998, 463-547.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: small;\">20. Watts R. Neutropenia. In Wintrobe\u2019s Clinical Hematology. Philadelphia ed. 2004, 1777-1795.<\/span><\/p>","protected":false},"excerpt":{"rendered":"<p>\u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u043f\u043e\u043a\u0430\u0437\u044b\u0432\u0430\u0435\u0442 \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u043e \u0438 \u0444\u0438\u0437\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0445\u0430\u0440\u0430\u043a\u0442\u0435\u0440\u0438\u0441\u0442\u0438\u043a\u0438 \u043a\u043b\u0435\u0442\u043e\u043a \u043a\u0440\u043e\u0432\u0438: \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432, \u043b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u043e\u0432, \u0442\u0440\u043e\u043c\u0431\u043e\u0446\u0438\u0442\u043e\u0432. \u0410\u043d\u0430\u043b\u0438\u0437 \u043f\u043e\u043c\u043e\u0433\u0430\u0435\u0442 \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u043e\u0431\u0449\u0435\u0435 \u0441\u043e\u0441\u0442\u043e\u044f\u043d\u0438\u0435 \u0437\u0434\u043e\u0440\u043e\u0432\u044c\u044f, \u0432\u044b\u044f\u0432\u0438\u0442\u044c \u0432\u043e\u0441\u043f\u0430\u043b\u0435\u043d\u0438\u044f, \u0438\u043d\u0442\u043e\u043a\u0441\u0438\u043a\u0430\u0446\u0438\u0438, \u0434\u0438\u0444\u0444\u0435\u0440\u0435\u043d\u0446\u0438\u0440\u043e\u0432\u0430\u0442\u044c \u0431\u0430\u043a\u0442\u0435\u0440\u0438\u0430\u043b\u044c\u043d\u044b\u0435 \u0438 \u0432\u0438\u0440\u0443\u0441\u043d\u044b\u0435 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u0438, \u043f\u043e\u043c\u043e\u0447\u044c \u0432 \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0435 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u0439 \u043a\u0440\u043e\u0432\u0435\u0442\u0432\u043e\u0440\u043d\u044b\u0445 \u043e\u0440\u0433\u0430\u043d\u043e\u0432, \u0430\u043b\u043b\u0435\u0440\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0440\u0435\u0430\u043a\u0446\u0438\u0439, \u0430\u0443\u0442\u043e\u0438\u043c\u043c\u0443\u043d\u043d\u044b\u0445 \u0431\u043e\u043b\u0435\u0437\u043d\u0435\u0439, \u043e\u043d\u043a\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u0439, \u0430 \u0442\u0430\u043a\u0436\u0435 \u043f\u0440\u043e\u043a\u043e\u043d\u0442\u0440\u043e\u043b\u0438\u0440\u043e\u0432\u0430\u0442\u044c \u0438\u0445 \u043b\u0435\u0447\u0435\u043d\u0438\u0435.<\/p>\n<p>\u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u043f\u0440\u043e\u0432\u043e\u0434\u044f\u0442, \u043a\u043e\u0433\u0434\u0430 \u043d\u0443\u0436\u043d\u043e \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u043e\u0431\u0449\u0435\u0435 \u0441\u043e\u0441\u0442\u043e\u044f\u043d\u0438\u0435 \u0437\u0434\u043e\u0440\u043e\u0432\u044c\u044f, \u0432\u044b\u044f\u0432\u0438\u0442\u044c \u0432\u043e\u0441\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0435 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f \u2014 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u043e\u043d\u043d\u044b\u0435, \u0430\u0443\u0442\u043e\u0438\u043c\u043c\u0443\u043d\u043d\u044b\u0435 \u0438 \u0434\u0440\u0443\u0433\u0438\u0435, \u043e\u0442\u0441\u043b\u0435\u0434\u0438\u0442\u044c \u0434\u0438\u043d\u0430\u043c\u0438\u043a\u0443 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f, \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u044d\u0444\u0444\u0435\u043a\u0442\u0438\u0432\u043d\u043e\u0441\u0442\u044c \u043b\u0435\u0447\u0435\u043d\u0438\u044f \u0438\u043b\u0438 \u043f\u0440\u043e\u0432\u0435\u0441\u0442\u0438 \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0443 \u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u0438 \u043a\u0440\u043e\u0432\u0435\u0442\u0432\u043e\u0440\u0435\u043d\u0438\u044f.<\/p>\n<p>\u041a\u0440\u043e\u0432\u044c \u2014 \u0431\u0438\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0430\u044f \u0436\u0438\u0434\u043a\u043e\u0441\u0442\u044c, \u043a\u043e\u0442\u043e\u0440\u0430\u044f \u0441\u043e\u0441\u0442\u043e\u0438\u0442 \u0438\u0437 \u043f\u043b\u0430\u0437\u043c\u044b \u2014 \u0436\u0438\u0434\u043a\u043e\u0433\u043e \u043c\u0435\u0436\u043a\u043b\u0435\u0442\u043e\u0447\u043d\u043e\u0433\u043e \u0432\u0435\u0449\u0435\u0441\u0442\u0432\u0430 \u2014 \u0438 \u0446\u0438\u0440\u043a\u0443\u043b\u0438\u0440\u0443\u044e\u0449\u0438\u0445 \u0432 \u043d\u0435\u0439 \u0444\u043e\u0440\u043c\u0435\u043d\u043d\u044b\u0445 \u044d\u043b\u0435\u043c\u0435\u043d\u0442\u043e\u0432: \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432, \u043b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u043e\u0432 \u0438 \u0442\u0440\u043e\u043c\u0431\u043e\u0446\u0438\u0442\u043e\u0432. \u041e\u0431\u0449\u0438\u0439 \u0430\u043d\u0430\u043b\u0438\u0437 \u043a\u0440\u043e\u0432\u0438 \u0438\u0437\u043c\u0435\u0440\u044f\u0435\u0442 \u0438\u0445 \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u043e, \u0444\u043e\u0440\u043c\u0443, \u0440\u0430\u0437\u043c\u0435\u0440 \u0438 \u0434\u0440\u0443\u0433\u0438\u0435 \u0445\u0430\u0440\u0430\u043a\u0442\u0435\u0440\u0438\u0441\u0442\u0438\u043a\u0438.<\/p>\n<p>\u041a\u0440\u043e\u0432\u044c \u043f\u043e\u0441\u0442\u043e\u044f\u043d\u043d\u043e \u043a\u043e\u043d\u0442\u0430\u043a\u0442\u0438\u0440\u0443\u0435\u0442 \u0441\u043e \u0432\u0441\u0435\u043c\u0438 \u0432\u043d\u0443\u0442\u0440\u0435\u043d\u043d\u0438\u043c\u0438 \u043e\u0440\u0433\u0430\u043d\u0430\u043c\u0438 \u0438 \u0441\u0438\u0441\u0442\u0435\u043c\u0430\u043c\u0438, \u043f\u043e\u044d\u0442\u043e\u043c\u0443 \u043b\u044e\u0431\u044b\u0435 \u0438\u0437\u043c\u0435\u043d\u0435\u043d\u0438\u044f \u0432 \u043e\u0440\u0433\u0430\u043d\u0438\u0437\u043c\u0435 \u043e\u0442\u0440\u0430\u0436\u0430\u044e\u0442\u0441\u044f \u043d\u0430 \u0435\u0451 \u0441\u043e\u0441\u0442\u0430\u0432\u0435. \u041a\u0440\u043e\u0432\u044c \u2014 \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u0439 \u0438 \u043d\u0430\u0438\u0431\u043e\u043b\u0435\u0435 \u0438\u043d\u0444\u043e\u0440\u043c\u0430\u0442\u0438\u0432\u043d\u044b\u0439 \u0438\u043d\u0434\u0438\u043a\u0430\u0442\u043e\u0440 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f \u043c\u043d\u043e\u0436\u0435\u0441\u0442\u0432\u0430 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u0439. \u0415\u0441\u043b\u0438 \u043e\u0434\u0438\u043d \u0438\u043b\u0438 \u043d\u0435\u0441\u043a\u043e\u043b\u044c\u043a\u043e \u043f\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u0435\u0439 \u043e\u0431\u0449\u0435\u0433\u043e \u0430\u043d\u0430\u043b\u0438\u0437\u0430 \u043a\u0440\u043e\u0432\u0438 \u043e\u0442\u043a\u043b\u043e\u043d\u044f\u044e\u0442\u0441\u044f \u043e\u0442 \u043d\u043e\u0440\u043c\u044b, \u0432\u0440\u0430\u0447 \u043c\u043e\u0436\u0435\u0442 \u043f\u043e\u0441\u0442\u0430\u0432\u0438\u0442\u044c \u043f\u0440\u0435\u0434\u0432\u0430\u0440\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0439 \u0434\u0438\u0430\u0433\u043d\u043e\u0437 \u0438 \u043d\u0430\u0437\u043d\u0430\u0447\u0438\u0442\u044c \u0434\u043e\u043f\u043e\u043b\u043d\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0435 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f.<\/p>\n<p>\u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u0435\u0442 \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u043f\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u0438 \u0442\u0440\u0451\u0445 \u043e\u0441\u043d\u043e\u0432\u043d\u044b\u0445 \u043a\u043e\u043c\u043f\u043e\u043d\u0435\u043d\u0442\u043e\u0432 \u043a\u0440\u043e\u0432\u0438: \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432, \u043b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u043e\u0432 \u0438 \u0442\u0440\u043e\u043c\u0431\u043e\u0446\u0438\u0442\u043e\u0432.<\/p>\n<p>\u042d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u044b \u2014 \u043a\u0440\u0430\u0441\u043d\u044b\u0435 \u043a\u0440\u043e\u0432\u044f\u043d\u044b\u0435 \u043a\u043b\u0435\u0442\u043a\u0438, \u043e\u0441\u043d\u043e\u0432\u043d\u0430\u044f \u0444\u0443\u043d\u043a\u0446\u0438\u044f \u043a\u043e\u0442\u043e\u0440\u044b\u0445 \u0441\u043e\u0441\u0442\u043e\u0438\u0442 \u0432 \u043f\u0435\u0440\u0435\u043d\u043e\u0441\u0435 \u043a\u0438\u0441\u043b\u043e\u0440\u043e\u0434\u0430 \u043a \u0442\u043a\u0430\u043d\u044f\u043c \u0438 \u0443\u0434\u0430\u043b\u0435\u043d\u0438\u0438 \u0443\u0433\u043b\u0435\u043a\u0438\u0441\u043b\u043e\u0433\u043e \u0433\u0430\u0437\u0430 \u0438\u0437 \u043d\u0438\u0445. \u0412 \u0440\u0430\u043c\u043a\u0430\u0445 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f \u0438\u0437\u0443\u0447\u0430\u044e\u0442 \u0438\u0445 \u0446\u0432\u0435\u0442, \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u043e, \u0440\u0430\u0437\u043c\u0435\u0440 \u0438 \u0434\u0440\u0443\u0433\u0438\u0435 \u0444\u0438\u0437\u0438\u043a\u043e-\u0445\u0438\u043c\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0441\u0432\u043e\u0439\u0441\u0442\u0432\u0430.<\/p>\n<p>\u0413\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d \u2014 \u0433\u043b\u0430\u0432\u043d\u044b\u0439 \u0431\u0435\u043b\u043e\u043a \u0432 \u0441\u043e\u0441\u0442\u0430\u0432\u0435 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432. \u041e\u043d \u043f\u0435\u0440\u0435\u043d\u043e\u0441\u0438\u0442 \u043e\u0442 \u043b\u0451\u0433\u043a\u0438\u0445 \u043a \u0442\u043a\u0430\u043d\u044f\u043c \u043a\u0438\u0441\u043b\u043e\u0440\u043e\u0434, \u0430 \u043e\u0431\u0440\u0430\u0442\u043d\u043e \u2014 \u0443\u0433\u043b\u0435\u043a\u0438\u0441\u043b\u044b\u0439 \u0433\u0430\u0437. \u0423\u0440\u043e\u0432\u0435\u043d\u044c \u0433\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d\u0430 \u043f\u043e\u043c\u043e\u0433\u0430\u0435\u0442 \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u043a\u0430\u0447\u0435\u0441\u0442\u0432\u043e \u0441\u043d\u0430\u0431\u0436\u0435\u043d\u0438\u044f \u043a\u043b\u0435\u0442\u043e\u043a \u043a\u0438\u0441\u043b\u043e\u0440\u043e\u0434\u043e\u043c, \u0430 \u0435\u0433\u043e \u0438\u0437\u043c\u0435\u043d\u0435\u043d\u0438\u0435 \u043c\u043e\u0436\u0435\u0442 \u0443\u043a\u0430\u0437\u044b\u0432\u0430\u0442\u044c \u043d\u0430 \u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u043f\u0440\u043e\u0446\u0435\u0441\u0441\u044b.<\/p>\n<p>\u0413\u0435\u043c\u0430\u0442\u043e\u043a\u0440\u0438\u0442 \u2014 \u043e\u0442\u043d\u043e\u0448\u0435\u043d\u0438\u0435 \u0444\u043e\u0440\u043c\u0435\u043d\u043d\u044b\u0445 \u044d\u043b\u0435\u043c\u0435\u043d\u0442\u043e\u0432 \u043a\u0440\u043e\u0432\u0438 (\u0432 \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u043c \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432) \u043a \u043f\u043b\u0430\u0437\u043c\u0435. \u041f\u043e\u0437\u0432\u043e\u043b\u044f\u0435\u0442 \u0441\u0443\u0434\u0438\u0442\u044c \u043e\u0431 \u0438\u0437\u0431\u044b\u0442\u043a\u0435 \u0438\u043b\u0438 \u0434\u0435\u0444\u0438\u0446\u0438\u0442\u0435 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432, \u0430 \u0442\u0430\u043a\u0436\u0435 \u043e\u0431\u0435\u0437\u0432\u043e\u0436\u0438\u0432\u0430\u043d\u0438\u0438 \u0438\u043b\u0438 \u0438\u0437\u0431\u044b\u0442\u043e\u0447\u043d\u043e\u043c \u0441\u043e\u0434\u0435\u0440\u0436\u0430\u043d\u0438\u0438 \u0432\u043e\u0434\u044b \u0432 \u043e\u0440\u0433\u0430\u043d\u0438\u0437\u043c\u0435.<\/p>\n<p>\u0426\u0432\u0435\u0442\u043e\u0432\u043e\u0439 \u043f\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u044c \u0438 MCH (Mean Cell Hemoglobin) \u2014 \u043f\u0430\u0440\u0430\u043c\u0435\u0442\u0440\u044b, \u043a\u043e\u0442\u043e\u0440\u044b\u0435 \u043e\u0442\u0440\u0430\u0436\u0430\u044e\u0442 \u043e\u0442\u043d\u043e\u0441\u0438\u0442\u0435\u043b\u044c\u043d\u043e\u0435 \u0441\u043e\u0434\u0435\u0440\u0436\u0430\u043d\u0438\u0435 \u0433\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d\u0430 \u0432 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u0430\u0445. \u041e\u043d\u0438 \u043f\u043e\u043c\u043e\u0433\u0430\u044e\u0442 \u0432\u044b\u044f\u0432\u0438\u0442\u044c \u0430\u043d\u0435\u043c\u0438\u044e \u0438 \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0438\u0442\u044c, \u043a \u043a\u0430\u043a\u043e\u043c\u0443 \u0442\u0438\u043f\u0443 \u043e\u043d\u0430 \u043e\u0442\u043d\u043e\u0441\u0438\u0442\u0441\u044f: \u0441 \u043d\u043e\u0440\u043c\u0430\u043b\u044c\u043d\u044b\u043c \u0441\u043e\u0434\u0435\u0440\u0436\u0430\u043d\u0438\u0435\u043c \u0433\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d\u0430 (\u043d\u043e\u0440\u043c\u043e\u0445\u0440\u043e\u043c\u043d\u0430\u044f), \u043f\u043e\u043d\u0438\u0436\u0435\u043d\u043d\u044b\u043c \u0441\u043e\u0434\u0435\u0440\u0436\u0430\u043d\u0438\u0435\u043c \u0433\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d\u0430 (\u0433\u0438\u043f\u043e\u0445\u0440\u043e\u043c\u043d\u0430\u044f) \u0438\u043b\u0438 \u043f\u043e\u0432\u044b\u0448\u0435\u043d\u043d\u044b\u043c \u0441\u043e\u0434\u0435\u0440\u0436\u0430\u043d\u0438\u0435\u043c \u0433\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d\u0430 (\u0433\u0438\u043f\u0435\u0440\u0445\u0440\u043e\u043c\u043d\u0430\u044f).<\/p>\n<p>MCV (Mean Cell Volume) \u2014 \u0441\u0440\u0435\u0434\u043d\u0438\u0439 \u043e\u0431\u044a\u0451\u043c \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u0430. \u0421\u043e\u0432\u043c\u0435\u0441\u0442\u043d\u043e \u0441 MCH \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u0435\u0442\u0441\u044f \u0434\u043b\u044f \u0432\u044b\u044f\u0432\u043b\u0435\u043d\u0438\u044f \u0430\u043d\u0435\u043c\u0438\u0438 \u0438 \u0435\u0451 \u043f\u0440\u0438\u0447\u0438\u043d.<\/p>\n<p>RDW (Red Cell Distribution Width) \u2014 \u0440\u0430\u0441\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u0438\u0435 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432 \u043f\u043e \u043e\u0431\u044a\u0451\u043c\u0443. \u041f\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u044c \u0432\u0430\u0436\u0435\u043d \u0432 \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0435 \u0430\u043d\u0435\u043c\u0438\u0438, \u0437\u0430\u0432\u0438\u0441\u0438\u0442 \u043e\u0442 \u0441\u0440\u0435\u0434\u043d\u0435\u0433\u043e \u043e\u0431\u044a\u0451\u043c\u0430 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u0430 (MCV). \u041f\u043e\u0432\u044b\u0448\u0435\u043d\u0438\u0435 \u043f\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u044f \u0443\u043a\u0430\u0437\u044b\u0432\u0430\u0435\u0442 \u043d\u0430 \u0442\u043e, \u0447\u0442\u043e \u0432 \u043a\u0440\u043e\u0432\u0438 \u043d\u0430\u0445\u043e\u0434\u044f\u0442\u0441\u044f \u043a\u043b\u0435\u0442\u043a\u0438 \u0440\u0430\u0437\u043d\u043e\u0433\u043e \u043e\u0431\u044a\u0451\u043c\u0430.<\/p>\n<p>MCHC (Mean Cell Hemoglobin Concentration) \u2014 \u0441\u0440\u0435\u0434\u043d\u044f\u044f \u043a\u043e\u043d\u0446\u0435\u043d\u0442\u0440\u0430\u0446\u0438\u044f \u0433\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d\u0430 \u0432 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u0430\u0445. \u0418\u0437\u043c\u0435\u043d\u0435\u043d\u0438\u0435 \u043f\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u044f \u043d\u0430\u0431\u043b\u044e\u0434\u0430\u0435\u0442\u0441\u044f \u043f\u0440\u0438 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0438 \u0441\u0438\u043d\u0442\u0435\u0437\u0430 \u0433\u0435\u043c\u043e\u0433\u043b\u043e\u0431\u0438\u043d\u0430, \u0433\u0438\u043f\u043e\u0445\u0440\u043e\u043c\u043d\u044b\u0445 \u0438 \u0433\u0438\u043f\u0435\u0440\u0445\u0440\u043e\u043c\u043d\u044b\u0445 \u0430\u043d\u0435\u043c\u0438\u044f\u0445.<\/p>\n<p>\u0420\u0435\u0442\u0438\u043a\u0443\u043b\u043e\u0446\u0438\u0442\u044b \u2014 \u043c\u043e\u043b\u043e\u0434\u044b\u0435 \u043a\u0440\u0430\u0441\u043d\u044b\u0435 \u043a\u043b\u0435\u0442\u043a\u0438, \u043f\u0440\u0435\u0434\u0448\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u0438\u043a\u0438 \u0437\u0440\u0435\u043b\u044b\u0445 \u044d\u0440\u0438\u0442\u0440\u043e\u0446\u0438\u0442\u043e\u0432. \u041f\u043e \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u0443 \u0440\u0435\u0442\u0438\u043a\u0443\u043b\u043e\u0446\u0438\u0442\u043e\u0432 \u0432 \u043a\u0440\u043e\u0432\u0438 \u043c\u043e\u0436\u043d\u043e \u0441\u0443\u0434\u0438\u0442\u044c \u043e \u0441\u043a\u043e\u0440\u043e\u0441\u0442\u0438 \u0441\u0438\u043d\u0442\u0435\u0437\u0430 \u043a\u0440\u0430\u0441\u043d\u044b\u0445 \u043a\u0440\u043e\u0432\u044f\u043d\u044b\u0445 \u0442\u0435\u043b\u0435\u0446 \u0438 \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u0440\u043e\u0432\u0430\u0442\u044c \u0430\u043d\u0435\u043c\u0438\u044e. \u0414\u043e\u043f\u043e\u043b\u043d\u0438\u0442\u0435\u043b\u044c\u043d\u043e \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u044f\u0435\u0442\u0441\u044f \u0440\u0435\u0442\u0438\u043a\u0443\u043b\u043e\u0446\u0438\u0442\u0430\u0440\u043d\u044b\u0439 \u0438\u043d\u0434\u0435\u043a\u0441 \u2014 \u043f\u0430\u0440\u0430\u043c\u0435\u0442\u0440, \u043a\u043e\u0442\u043e\u0440\u044b\u0439 \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u0435\u0442 \u0431\u043e\u043b\u0435\u0435 \u0442\u043e\u0447\u043d\u043e \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u0442\u044f\u0436\u0435\u0441\u0442\u044c \u0430\u043d\u0435\u043c\u0438\u0438. \u0412 \u0441\u043e\u0432\u043e\u043a\u0443\u043f\u043d\u043e\u0441\u0442\u0438 \u044d\u0442\u0438 \u0434\u0430\u043d\u043d\u044b\u0435 \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u044e\u0442\u0441\u044f \u0434\u043b\u044f \u0432\u0435\u0434\u0435\u043d\u0438\u044f \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u043e\u0432 \u0441 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0435\u043c \u043f\u0440\u043e\u0446\u0435\u0441\u0441\u043e\u0432 \u043a\u0440\u043e\u0432\u0435\u0442\u0432\u043e\u0440\u0435\u043d\u0438\u044f.<\/p>\n<p>\u041b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u044b \u2014 \u043a\u043b\u0435\u0442\u043a\u0438, \u043a\u043e\u0442\u043e\u0440\u044b\u0435 \u0442\u0430\u043a\u0436\u0435 \u043d\u0430\u0437\u044b\u0432\u0430\u044e\u0442 \u0431\u0435\u043b\u044b\u043c\u0438 \u043a\u0440\u043e\u0432\u044f\u043d\u044b\u043c\u0438 \u0442\u0435\u043b\u044c\u0446\u0430\u043c\u0438. \u041e\u043d\u0438 \u0443\u0447\u0430\u0441\u0442\u0432\u0443\u044e\u0442 \u0432 \u0438\u043c\u043c\u0443\u043d\u043d\u044b\u0445 \u043f\u0440\u043e\u0446\u0435\u0441\u0441\u0430\u0445 \u0438 \u0437\u0430\u0449\u0438\u0449\u0430\u044e\u0442 \u043e\u0440\u0433\u0430\u043d\u0438\u0437\u043c \u043e\u0442 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u0439. \u0421\u0443\u0449\u0435\u0441\u0442\u0432\u0443\u0435\u0442 \u043d\u0435\u0441\u043a\u043e\u043b\u044c\u043a\u043e \u0442\u0438\u043f\u043e\u0432 \u043b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u043e\u0432: \u044d\u043e\u0437\u0438\u043d\u043e\u0444\u0438\u043b\u044b, \u043d\u0435\u0439\u0442\u0440\u043e\u0444\u0438\u043b\u044b, \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b, \u0431\u0430\u0437\u043e\u0444\u0438\u043b\u044b, \u043c\u043e\u043d\u043e\u0446\u0438\u0442\u044b.<\/p>\n<p>\u041d\u0435\u0439\u0442\u0440\u043e\u0444\u0438\u043b\u044b \u2014 \u0441\u0430\u043c\u0430\u044f \u043c\u043d\u043e\u0433\u043e\u0447\u0438\u0441\u043b\u0435\u043d\u043d\u0430\u044f \u043f\u043e\u043f\u0443\u043b\u044f\u0446\u0438\u044f \u043b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u043e\u0432, \u0431\u043e\u0440\u044e\u0449\u0430\u044f\u0441\u044f \u0441 \u0447\u0443\u0436\u0435\u0440\u043e\u0434\u043d\u044b\u043c\u0438 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\u043d\u0435\u0433\u0430\u0437\u0438\u0440\u043e\u0432\u0430\u043d\u043d\u0443\u044e \u0432\u043e\u0434\u0443. \u041d\u0430\u043a\u0430\u043d\u0443\u043d\u0435 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f \u043b\u0443\u0447\u0448\u0435 \u043f\u043e\u0443\u0436\u0438\u043d\u0430\u0442\u044c \u043b\u0451\u0433\u043a\u043e\u0439, \u043d\u0435\u0436\u0438\u0440\u043d\u043e\u0439 \u043f\u0438\u0449\u0435\u0439.<\/li>\n<li>\u0417\u0430 1\u20132 \u0447\u0430\u0441\u0430 \u0434\u043e \u0430\u043d\u0430\u043b\u0438\u0437\u0430 \u0436\u0435\u043b\u0430\u0442\u0435\u043b\u044c\u043d\u043e \u043d\u0435 \u043a\u0443\u0440\u0438\u0442\u044c, \u0438\u0437\u0431\u0435\u0433\u0430\u0442\u044c \u0441\u0442\u0440\u0435\u0441\u0441\u0430 \u0438 \u0444\u0438\u0437\u0438\u0447\u0435\u0441\u043a\u043e\u0433\u043e \u043d\u0430\u043f\u0440\u044f\u0436\u0435\u043d\u0438\u044f (\u0431\u0435\u0433, \u0431\u044b\u0441\u0442\u0440\u044b\u0439 \u043f\u043e\u0434\u044a\u0451\u043c \u043f\u043e \u043b\u0435\u0441\u0442\u043d\u0438\u0446\u0435).<\/li>\n<li>\u0417\u0430 15 \u043c\u0438\u043d\u0443\u0442 \u0434\u043e \u0432\u0437\u044f\u0442\u0438\u044f \u043a\u0440\u043e\u0432\u0438 \u0436\u0435\u043b\u0430\u0442\u0435\u043b\u044c\u043d\u043e \u043d\u0435\u043c\u043d\u043e\u0433\u043e \u043e\u0442\u0434\u043e\u0445\u043d\u0443\u0442\u044c: \u043f\u043e\u0441\u0438\u0434\u0435\u0442\u044c \u0432 \u043b\u0430\u0431\u043e\u0440\u0430\u0442\u043e\u0440\u043d\u043e\u043c \u043e\u0442\u0434\u0435\u043b\u0435\u043d\u0438\u0438, \u043e\u0442\u0434\u044b\u0448\u0430\u0442\u044c\u0441\u044f, \u0443\u0441\u043f\u043e\u043a\u043e\u0438\u0442\u044c\u0441\u044f.<\/li>\n<\/ol>\n<p>\u041f\u0440\u0430\u0432\u0438\u043b\u0430 \u0432\u0437\u044f\u0442\u0438\u044f \u043a\u0440\u043e\u0432\u0438 \u0443 \u0434\u0435\u0442\u0435\u0439:<\/p>\n<ul>\n<li>\u043c\u043b\u0430\u0434\u0435\u043d\u0446\u044b \u0434\u043e 1 \u0433\u043e\u0434\u0430<\/li>\n<li>\u0434\u0435\u0442\u0438 \u0434\u043e 7 \u043b\u0435\u0442<\/li>\n<\/ul>\n<p>\u0414\u043b\u044f \u043a\u043e\u043d\u0442\u0440\u043e\u043b\u044f \u043f\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u0435\u0439 \u0432 \u0434\u0438\u043d\u0430\u043c\u0438\u043a\u0435 \u0441\u043b\u0435\u0434\u0443\u0435\u0442 \u0441\u0434\u0430\u0432\u0430\u0442\u044c \u0430\u043d\u0430\u043b\u0438\u0437 \u0432 \u043e\u0434\u0438\u043d\u0430\u043a\u043e\u0432\u044b\u0445 \u0443\u0441\u043b\u043e\u0432\u0438\u044f\u0445: \u0432 \u0442\u043e\u0439 \u0436\u0435 \u043b\u0430\u0431\u043e\u0440\u0430\u0442\u043e\u0440\u0438\u0438, \u0432 \u0442\u043e \u0436\u0435 \u0432\u0440\u0435\u043c\u044f \u0441\u0443\u0442\u043e\u043a. \u0416\u0435\u043d\u0449\u0438\u043d\u0430\u043c \u0441\u0442\u043e\u0438\u0442 \u0443\u0447\u0435\u0441\u0442\u044c \u0444\u0430\u0437\u0443 \u043c\u0435\u043d\u0441\u0442\u0440\u0443\u0430\u043b\u044c\u043d\u043e\u0433\u043e \u0446\u0438\u043a\u043b\u0430.<\/p>","protected":false},"featured_media":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_brand":[],"product_cat":[948],"product_tag":[],"class_list":{"0":"post-9253","1":"product","2":"type-product","3":"status-publish","5":"product_cat-morfofiziologie","7":"first","8":"instock","9":"sold-individually","10":"shipping-taxable","11":"purchasable","12":"product-type-simple"},"_links":{"self":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product\/9253","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/comments?post=9253"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=9253"}],"wp:term":[{"taxonomy":"product_brand","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_brand?post=9253"},{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_cat?post=9253"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_tag?post=9253"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}