{"id":10009,"date":"2020-04-23T03:53:50","date_gmt":"2020-04-23T01:53:50","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/factor-viii-inhibitori\/"},"modified":"2025-07-11T14:24:10","modified_gmt":"2025-07-11T11:24:10","slug":"factor-viii-inhibitori","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/factor-viii-inhibitori\/","title":{"rendered":"\u0418\u043d\u0433\u0438\u0431\u0438\u0442\u043e\u0440 \u0444\u0430\u043a\u0442\u043e\u0440\u0430 VIII"},"content":{"rendered":"<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Informa\u0163<\/em><\/strong><strong><em>ii generale<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Inhibitorii factorului VIII (anticorpi) apar la bolnavii cu hemofilie tip A ca o consecin\u0163\u0103 a terapiei cu concentrat de factor VIII, reprezent\u00e2nd o complica\u0163ie redutabil\u0103 care pune probleme serioase de tratament<sup>7<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Este vorba despre dezvoltarea unor aloanticorpi cu ac\u0163iune de neutralizare a FVIII-C \u015fi structura de tip IgG. Anticorpii sunt oligoclonali \u015fi pot apar\u0163ine subclaselor IgG<sub>1<\/sub>, IgG<sub>3 <sup>\u015f<\/sup><\/sub>i IgG<sub>4\u00a0<\/sub>nu fixeaz\u0103 complementul \u015fi de aceea bolnavii nu fac boala serului sau a complexelor imune. Induc hemoragii asem\u0103n\u0103toare deficitului de factor VIII \u2013 mai rar hemartroze \u2013 \u015fi o prelungire a timpului de tromboplastin\u0103 par\u0163ial\u0103 activat (aPTT)<sup>1;5;7<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Aloimunizarea fa\u0163\u0103 de FVIII este idiosincratic\u0103 \u015fi se produce la 15-20% din pacien\u0163ii (\u00een special copii) cu hemofilie sever\u0103. Riscul apari\u0163iei de anticorpi este extrem de variabil; datele concrete ob\u0163inute p\u00e2n\u0103 \u00een prezent arat\u0103 urm\u0103toarele:<\/span><\/p>\n<ul>\n<li style=\"text-align: justify;\"><span style=\"font-size: medium;\">nu exist\u0103 nici o implica\u0163ie familial\u0103 absolut\u0103, de\u015fi nu poate fi negat\u0103 o oarecare tendin\u0163\u0103 constitu\u0163ional\u0103 \u00een acest sens; bolnavii al c\u0103ror deficit de FVIII se datoreaz\u0103 unor dele\u0163ii sau muta\u0163ii nonsens fac mai u\u015for inhibitori;<\/span><\/li>\n<li style=\"text-align: justify;\">nu exist\u0103 o leg\u0103tur\u0103 cu sistemul HLA; mai cur\u00e2nd \u00een cadrul grupelor sanguine clasice balan\u0163a \u00eenclin\u0103 c\u0103tre grupa AB(IV);<\/li>\n<li style=\"text-align: justify;\">v\u00e2rsta pacientului prezint\u0103 o oarecare influen\u0163\u0103; grupele 1-5 ani \u015fi cele peste 40 ani sunt mai frecvent afectate;<\/li>\n<li style=\"text-align: justify;\">nu este important\u0103 doza de preparat antihemofilic administrat, ci durata lung\u0103 a tratamentului (num\u0103rul mare de perfuzii);<\/li>\n<li style=\"text-align: justify;\">tipurile clinice de hemofilie sever\u0103 \u015fi medie prezint\u0103 incidente mai mari (18%) dec\u00e2t cele u\u015foare(1%);<\/li>\n<li style=\"text-align: justify;\">puritatea factorului antihemofilic folosit \u00een tratament este direct propor\u0163ional\u0103 cu frecven\u0163a apari\u0163iei de inhibitori; preparatele mai pu\u0163in pure induc un r\u0103spuns imun umoral mai mic;<\/li>\n<li style=\"text-align: justify;\">la mul\u0163i pacien\u0163i cu inhibitori ai FVIII dezvoltarea acestora este sugerat\u0103 de lipsa de r\u0103spuns la tratamentul cu FVIII care fusese p\u00e2n\u0103 atunci eficient; aPTT prelungit nu se corecteaz\u0103 \u00een vitro dup\u0103 ad\u0103ugarea de plasm\u0103, iar prezen\u0163a inhibitorilor este confirmat\u0103 cu testul Bethesda<sup>4;6<\/sup><span style=\"font-size: medium;\">.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Tratamentul s\u00e2nger\u0103rilor acute la hemofiliticii cu inhibitori este dificil \u015fi costisitor; depinde de nivelul inhibitorilor \u015fi de rapiditatea cu care pacien\u0163ii dezvolt\u0103 anticorpi la fiecare doz\u0103 administrat\u0103 (\u201chigh-responders\u201d vs \u201clow-responders\u201d).<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Exist\u0103 2 tipuri principale de tratament la pacien\u0163ii \u201chigh-responders\u201d:<\/span><\/p>\n<ul>\n<li style=\"text-align: justify;\"><span style=\"font-size: medium;\">concentrate de complex de protrombin\u0103 activat;<\/span><\/li>\n<li style=\"text-align: justify;\"><span style=\"font-size: medium;\">factor VIIa recombinat (NovoSeven).<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">La fiecare pacient cu inhibitori trebuie luat\u0103 \u00een considerare posibilitatea de eliminare a acestora prin toleran\u0163a imun\u0103. Sunt disponibile 3 protocoale de inducere a toleran\u0163ei imune:<\/span><\/p>\n<ul style=\"text-align: justify;\">\n<li><span style=\"font-size: medium;\">protocol cu doze mari: administrarea zilnic\u0103 de FVIII;<\/span><\/li>\n<li><span style=\"font-size: medium;\">protocol cu doze mici: administrarea de FVIII la 2 zile;<\/span><\/li>\n<li><span style=\"font-size: medium;\">protocol Malmo: FVIII este combinat cu imunoglobulin\u0103 i.v., ciclofosfamid\u0103, imunoabsorb\u0163ie sau plasmaferez\u0103.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Rata de succes \u00eenregistrat\u0103 cu aceste protocoale este de 30-80%; odat\u0103 elimina\u0163i inhibitorii, exist\u0103 un risc de recuren\u0163\u0103 de 15%<sup>6<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Preg\u0103tire pacient<\/em><\/strong> <em>- <\/em>\u00e0 jeun (pe nem\u00e2ncate)<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Specimen recoltat<\/em><\/strong> <em>- <\/em>\u0432\u0435\u043d\u043e\u0437\u043d\u0430\u044f \u043a\u0440\u043e\u0432\u044c<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Recipient de recoltare<\/em><\/strong> \u2013 vacutainer cu citrat de Na 0.105M (raport citrat de sodiu \u2013 sange=1\/9). Presiunea realizat\u0103 de garou trebuie s\u0103 fie \u00eentre valoarea presiunii sistolice \u015fi cea a presiunii diastolice \u015fi nu trebuie s\u0103 dep\u0103\u015feasc\u0103 1 minut. Dac\u0103 punc\u0163ia venoas\u0103 a e\u015fuat, o nou\u0103 tentativ\u0103 pe aceea\u015fi ven\u0103 nu se poate face dec\u00e2t dup\u0103 10 minute<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Cantitate recoltat\u0103<\/em><\/strong> \u2013 c\u00e2t permite vacuumul; pentru a preveni coagularea par\u0163ial\u0103 a probei se va asigura amestecul corect al s\u00e2ngelui cu anticoagulantul, prin mi\u015fc\u0103ri de inversiune a tubului<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Prelucrare necesar\u0103 dup\u0103 recoltare <\/em><\/strong>\u2013 proba va fi centrifugat\u0103 15 minute la 2500g, urmat\u0103 imediat de separarea plasmei \u015fi congelarea acesteia; probele recoltate \u00een afara laboratorului vor fi transportate\u00a0\u00een r<\/span><span style=\"font-size: medium;\">ecipientul destinat probelor congelate<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Cauze de respingere a probei<\/em><\/strong> <em>- <\/em>vacutainer care nu este plin; proba de s\u00e2nge hemolizat\u0103 sau coagulat\u0103; plasma care nu a ajuns congelat\u0103 la laborator<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Stabilitate prob\u0103<\/em><\/strong> \u2013 plasma separat\u0103 este stabil\u0103 <em>4 ore<\/em> la temperatura camerei; <em>3 s\u0103pt\u0103m\u00e2ni<\/em> la\u00a0 \u2013 20\u00baC; <em>&gt;1 an<\/em> la \u2013 70\u00baC<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Valori de referin\u0163\u0103 \u2013 <\/em><\/strong><\/span><span style=\"font-size: medium;\">FVIII inhibitori \u2013 negativ<sup>2<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Metoda<\/em><\/strong><\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Principial prezen\u0163a oric\u0103rui anticoagulant circulant se pune \u00een eviden\u0163\u0103 prin inhibi\u0163ia exercitat\u0103 de plasma de testat asupra unui sistem de coagulare normal; toate tehnicile de studiu ale unui anticoagulant circulant se bazeaz\u0103 pe acela\u015fi principiu, dar testul folosit variaz\u0103, dup\u0103 cum este vorba, de realizarea unei detec\u0163ii calitative sau cantitative (aceasta din urm\u0103 permite determinarea nivelului de activitate a inhibitorului). Depistarea apari\u0163iei inhibitorilor se desf\u0103\u015foar\u0103 \u00een dou\u0103 etape:<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">- <strong>Etapa calitativ\u0103 <\/strong>este bazat\u0103 pe testul aPTT: se determin\u0103 valoarea aPTT la un martor normal, la pacient \u015fi la un amestec 1\/1 al plasmelor celor doi de mai sus incubat la 37<sup>0<\/sup>C timp de o or\u0103; dac\u0103 valoarea aPTT a acestui amestec se apropie de cea a normalului (abatere maxim\u0103 + 10%), proba este negativ\u0103 \u015fi deci pacientul nu are inhibitori; men\u0163inerea valorii aPTT a amestecului \u00een vecinatatea celei a bolnavului (abatere \u2013 20%) indic\u0103 prezen\u0163a de anticorpi, deci proba este pozitiv\u0103 \u015fi se trece la etapa urm\u0103toare.<\/span><\/p>\n<p style=\"text-align: justify; padding-left: 30px;\"><span style=\"font-size: medium;\">- <strong>Etapa cantitativ\u0103<\/strong> bazat\u0103 pe urm\u0103torul principiu: dac\u0103 FVIII (de fapt, plasma normal\u0103 cu activitate FVIII 100%) este adaug\u0103t la plasma care prezint\u0103 inhibitor \u015fi amestecul este incubat la 37<sup>0<\/sup>C, FVIII va fi neutralizat progresiv. 1<sup>,2,3,7<\/sup> FVIII rezidual se ob\u0163ine\u00a0 prin determinarea activit\u0103\u0163ii FVIII din amestecul plasm\u0103 pacient \u015fi FVIII dup\u0103 incubare.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">Metoda cantitativ\u0103\u00a0<strong>\u00a0<\/strong>este de fapt o titrare \u00een care se folose\u015fte tehnica de determinare a nivelului de FVIII-C \u00een<\/span><span style=\"font-size: medium;\">tr-o baterie de dilu\u0163ii seriale ale plasmei pacientului numit\u0103 metoda Bethesda, rezultatul exprim\u00e2ndu-se \u00een unit\u0103\u0163i Bethesda\/mL (UB\/mL). O unitate Bethesda reprezint\u0103 cantitatea de anticorpi care inactiveaz\u0103 \u00een 2 ore la 37<sup>0<\/sup>C jum\u0103tate din nivelul de FVIII al unei plasme normale (factor VIII rezidual 50%).<sup>2,3 <\/sup>Dac\u0103 aceea\u015fi plasm\u0103 a fost diluat\u0103 de 10 ori \u00eenaintea test\u0103rii pentru inhibitori, acest rezultat va indica o valoare a inhibitorului de 10 UB\/mL. Pentru deciderea nivelului unit\u0103\u0163ilor Bethesda \u015fi calcularea titrului de inhibitor se alege dilu\u0163ia cea mai apropiat\u0103 de activitatea factorui VIII rezidual de 50%<sup>1;3;5;6;7<\/sup>.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\"><strong><em>Interpretarea rezultatelor<\/em><\/strong><\/span><\/p>\n<div style=\"text-align: justify;\"><span style=\"font-size: medium;\">Pacien\u0163ii cu titruri de inhibitori &lt; 5 UB\/mL sunt clasificati ca \u201clow-responders\u201d, pe c\u00e2nd cei cu titruri &gt; 10 UB\/mL <\/span><span style=\"font-size: medium;\">sunt considera\u0163i ca fiind \u201chigh-responders\u201d<sup>6<\/sup>.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: medium;\">Pe baza rezultatelor ob\u0163inute cu aceast\u0103 metod\u0103 se stabile\u015fte schema de tratament a bolnavului.<\/span><\/div>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00cen ceea ce prive\u015fte tratamentul cu FVIII este important de re\u0163inut:<\/span><\/p>\n<ul>\n<li style=\"text-align: justify;\"><span style=\"font-size: medium;\">plasma cu activitate de coagulare 100% are o unitate\/mL din factorul de coagulare. Conven\u0163ional o unitate de factor de coagulare este cantitatea respectivului factor prezent \u00een 1mL\u00a0 plasma normal\u0103. Fiecare unitate de FVIII recombinat\/kg corp m\u0103re\u015fte cu 2% activitatea plasmatic\u0103 a FVIII.<\/span><\/li>\n<li style=\"text-align: justify;\">timpul de \u00eenjum\u0103t\u0103\u0163ire a FVIII este de 12 ore<sup>5;7<\/sup><span style=\"font-size: medium;\">.<\/span><\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><span style=\"font-size: medium;\">\u00a0<\/span><strong><span style=\"font-size: small;\">\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/span><\/strong><\/p>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">1. Delia Mut Popescu. Hematologie clinic\u0103. Note de curs. Edi\u0163ia a II-a, Editura Medical\u0103 2003, 307.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">2. Laborator Synevo. Referin\u0163ele specifice tehnologiei de lucru utilizate 2010. Ref Type: Catalog.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">3. Laboratory Corporation of America. Directory of Services and Interpretive Guide. Factor VIII Inhibitor Profile, <\/span><span style=\"font-size: small;\">Comprehensive. www.labcorp.com. 2010. Ref Type: Internet Communication.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">4. Radu P\u0103un. Tratat de Medicin\u0103 Intern\u0103. Hematologie. Partea I, 1997, Editura Medical\u0103, 529.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">5. Radu P\u0103un. Tratat de medicin\u0103 intern\u0103 . Hematologie. Partea II, 1999,\u00a0Editura Medical\u0103, 779-854.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">6. Rhona M. Maclean, Michael Makris. Hemophilia A and B. In Practical Hemostasis and Thrombosis, Blackwell Publishing, 2008, 48.<\/span><\/div>\n<div style=\"text-align: justify;\"><span style=\"font-size: small;\">7. Richard A. McPetersen, Matthew R. Pincus. Coagulation and Fibrinolysis. In Clinical diagnosis and management by <\/span><span style=\"font-size: small;\">laboratory methods. 2007, 729-743.<\/span><\/div>","protected":false},"excerpt":{"rendered":"<p>\u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u043f\u0440\u0438\u043c\u0435\u043d\u044f\u044e\u0442 \u0434\u043b\u044f \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0438 \u0433\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u0438 \u0442\u0438\u043f\u0430 \u0410, \u043f\u0440\u0438\u043e\u0431\u0440\u0435\u0442\u0435\u043d\u043d\u044b\u0445 \u0433\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0440\u0430\u0441\u0441\u0442\u0440\u043e\u0439\u0441\u0442\u0432, \u043f\u0440\u0438 \u043e\u0431\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0438 \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u043e\u0432 \u0441 \u0443\u0434\u043b\u0438\u043d\u0435\u043d\u043d\u044b\u043c \u0410\u0427\u0422\u0412.<\/p>\n<p>\u0424\u0430\u043a\u0442\u043e\u0440 \u0441\u0432\u0435\u0440\u0442\u044b\u0432\u0430\u043d\u0438\u044f VIII (FVIII), \u043d\u0430\u0437\u044b\u0432\u0430\u0435\u043c\u044b\u0439 \u0442\u0430\u043a\u0436\u0435 \u0430\u043d\u0442\u0438\u0433\u0435\u043c\u043e\u0444\u0438\u043b\u044c\u043d\u044b\u043c \u0433\u043b\u043e\u0431\u0443\u043b\u0438\u043d\u043e\u043c \u2013 \u0433\u043b\u0438\u043a\u043e\u043f\u0440\u043e\u0442\u0435\u0438\u043d \u043f\u043b\u0430\u0437\u043c\u044b, \u043a\u043e\u0442\u043e\u0440\u044b\u0439 \u043e\u0442\u043d\u043e\u0441\u0438\u0442\u0441\u044f \u043a \u0444\u0430\u043a\u0442\u043e\u0440\u0430\u043c \u0432\u043d\u0443\u0442\u0440\u0435\u043d\u043d\u0435\u0433\u043e \u043f\u0443\u0442\u0438 \u043f\u043b\u0430\u0437\u043c\u0435\u043d\u043d\u043e\u0433\u043e \u0437\u0432\u0435\u043d\u0430 \u043a\u0430\u0441\u043a\u0430\u0434\u0430 \u0441\u0432\u0451\u0440\u0442\u044b\u0432\u0430\u043d\u0438\u044f. FVIII \u0441\u0438\u043d\u0442\u0435\u0437\u0438\u0440\u0443\u0435\u0442\u0441\u044f \u043f\u0440\u0435\u0438\u043c\u0443\u0449\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u043e \u0432 \u043f\u0435\u0447\u0435\u043d\u0438, \u0446\u0438\u0440\u043a\u0443\u043b\u0438\u0440\u0443\u0435\u0442 \u0432 \u043a\u0440\u043e\u0432\u0438 \u0432 \u0432\u0438\u0434\u0435 \u043a\u043e\u043c\u043f\u043b\u0435\u043a\u0441\u0430 \u0441 \u0444\u0430\u043a\u0442\u043e\u0440\u043e\u043c \u0412\u0438\u043b\u043b\u0435\u0431\u0440\u0430\u043d\u0434\u0430, \u0432 \u043f\u0440\u043e\u0446\u0435\u0441\u0441\u0435 \u0441\u0432\u0435\u0440\u0442\u044b\u0432\u0430\u043d\u0438\u044f \u043a\u0440\u043e\u0432\u0438 \u043f\u0435\u0440\u0435\u0445\u043e\u0434\u0438\u0442 \u0432 \u0430\u043a\u0442\u0438\u0432\u043d\u0443\u044e \u0444\u043e\u0440\u043c\u0443 \u0438 \u0434\u0435\u0439\u0441\u0442\u0432\u0443\u0435\u0442 \u043a\u0430\u043a \u043a\u043e-\u0444\u0430\u043a\u0442\u043e\u0440 \u0434\u043b\u044f \u0444\u0430\u043a\u0442\u043e\u0440\u0430 IX, \u043c\u043d\u043e\u0433\u043e\u043a\u0440\u0430\u0442\u043d\u043e \u0443\u0441\u043a\u043e\u0440\u044f\u044f \u0435\u0433\u043e \u0430\u043a\u0442\u0438\u0432\u0430\u0446\u0438\u044e.<\/p>\n<p>\u0412\u0440\u043e\u0436\u0434\u0435\u043d\u043d\u044b\u0439 \u0434\u0435\u0444\u0438\u0446\u0438\u0442 FVIII \u044f\u0432\u043b\u044f\u0435\u0442\u0441\u044f \u043f\u0440\u0438\u0447\u0438\u043d\u043e\u0439 \u0433\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u0438 \u0410. \u042d\u0442\u043e \u043d\u0430\u0441\u043b\u0435\u0434\u0441\u0442\u0432\u0435\u043d\u043d\u043e\u0435 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u0435, \u043f\u0440\u043e\u044f\u0432\u043b\u044f\u044e\u0449\u0435\u0435\u0441\u044f \u043a\u0440\u043e\u0432\u043e\u0438\u0437\u043b\u0438\u044f\u043d\u0438\u044f\u043c\u0438 \u0432\u043e \u0432\u043d\u0443\u0442\u0440\u0435\u043d\u043d\u0438\u0435 \u043e\u0440\u0433\u0430\u043d\u044b, \u043a\u0440\u043e\u0432\u043e\u0442\u0435\u0447\u0435\u043d\u0438\u044f\u043c\u0438, \u043a\u0430\u043a \u0441\u043f\u043e\u043d\u0442\u0430\u043d\u043d\u044b\u043c\u0438, \u0442\u0430\u043a \u0438 \u0432\u044b\u0437\u0432\u0430\u043d\u043d\u044b\u043c\u0438 \u0442\u0440\u0430\u0432\u043c\u0430\u043c\u0438 \u0438\u043b\u0438 \u0445\u0438\u0440\u0443\u0440\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u043c\u0438 \u0432\u043c\u0435\u0448\u0430\u0442\u0435\u043b\u044c\u0441\u0442\u0432\u0430\u043c\u0438, \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0438\u0432\u0430\u0435\u0442\u0441\u044f \u043e\u0431\u044b\u0447\u043d\u043e \u0432 \u0440\u0430\u043d\u043d\u0435\u043c \u0432\u043e\u0437\u0440\u0430\u0441\u0442\u0435. \u0420\u0430\u0437\u043b\u0438\u0447\u0430\u044e\u0442 \u0442\u044f\u0436\u0435\u043b\u0443\u044e, \u0443\u043c\u0435\u0440\u0435\u043d\u043d\u0443\u044e \u0438 \u043b\u0435\u0433\u043a\u0443\u044e \u0444\u043e\u0440\u043c\u044b \u0433\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u0438 \u0410. \u0422\u044f\u0436\u0435\u0441\u0442\u044c \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f \u043e\u0431\u0440\u0430\u0442\u043d\u043e \u0441\u0432\u044f\u0437\u0430\u043d\u0430 \u0441 \u0443\u0440\u043e\u0432\u043d\u0435\u043c FVIII (\u043f\u043e\u0434\u0440\u043e\u0431\u043d\u0435\u0435 \u0441\u043c. \u0440\u0430\u0437\u0434\u0435\u043b \u0418\u043d\u0442\u0435\u0440\u043f\u0440\u0435\u0442\u0430\u0446\u0438\u044f). \u0413\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u044f \u0410 (\u0434\u0435\u0444\u0438\u0446\u0438\u0442 FVIII) \u0432\u0441\u0442\u0440\u0435\u0447\u0430\u0435\u0442\u0441\u044f \u0432 4\u20135 \u0440\u0430\u0437 \u0447\u0430\u0449\u0435 \u0433\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u0438 \u0412 (\u0434\u0435\u0444\u0438\u0446\u0438\u0442 FIX). \u0422\u0438\u043f \u043d\u0430\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f \u2013 \u0430\u0443\u0442\u043e\u0441\u043e\u043c\u043d\u043e-\u0440\u0435\u0446\u0435\u0441\u0441\u0438\u0432\u043d\u044b\u0439, \u0441\u0446\u0435\u043f\u043b\u0435\u043d\u043d\u044b\u0439 \u0441 \u0425-\u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043e\u0439. \u0413\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f \u0441 \u0442\u0430\u043a\u0438\u043c \u0442\u0438\u043f\u043e\u043c \u043d\u0430\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f \u043f\u0440\u043e\u044f\u0432\u043b\u044f\u044e\u0442\u0441\u044f \u043f\u0440\u0435\u0438\u043c\u0443\u0449\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u043e \u0443 \u043c\u0443\u0436\u0447\u0438\u043d, \u0436\u0435\u043d\u0449\u0438\u043d\u044b \u044f\u0432\u043b\u044f\u044e\u0442\u0441\u044f \u043b\u0438\u0448\u044c \u043d\u043e\u0441\u0438\u0442\u0435\u043b\u044f\u043c\u0438 (\u0437\u0430 \u043a\u0440\u0430\u0439\u043d\u0435 \u0440\u0435\u0434\u043a\u0438\u043c\u0438 \u0438\u0441\u043a\u043b\u044e\u0447\u0435\u043d\u0438\u044f\u043c\u0438). \u0427\u0430\u0441\u0442\u043e\u0442\u0430 \u0432\u0441\u0442\u0440\u0435\u0447\u0430\u0435\u043c\u043e\u0441\u0442\u0438 \u043a\u043b\u0430\u0441\u0441\u0438\u0447\u0435\u0441\u043a\u043e\u0439 \u0433\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u0438 \u0410 \u2013 14:100000 \u0441\u0440\u0435\u0434\u0438 \u043c\u0443\u0436\u0447\u0438\u043d, \u0435\u0434\u0438\u043d\u0438\u0447\u043d\u044b\u0435 \u0441\u043b\u0443\u0447\u0430\u0438 \u044d\u0442\u043e\u0433\u043e \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f \u043e\u043f\u0438\u0441\u0430\u043d\u044b \u0443 \u0436\u0435\u043d\u0449\u0438\u043d.<\/p>\n<p>\u041f\u0440\u0438\u043e\u0431\u0440\u0435\u0442\u0435\u043d\u043d\u0430\u044f \u043d\u0435\u0434\u043e\u0441\u0442\u0430\u0442\u043e\u0447\u043d\u043e\u0441\u0442\u044c FVIII \u2013 \u0440\u0435\u0434\u043a\u043e\u0435, \u043d\u043e \u0442\u044f\u0436\u0435\u043b\u043e\u0435 \u0430\u0443\u0442\u043e\u0438\u043c\u043c\u0443\u043d\u043d\u043e\u0435 \u0440\u0430\u0441\u0441\u0442\u0440\u043e\u0439\u0441\u0442\u0432\u043e, \u043a\u043e\u0442\u043e\u0440\u043e\u0435 \u0441\u0432\u044f\u0437\u0430\u043d\u043e \u0441 \u043f\u0440\u0438\u0441\u0443\u0442\u0441\u0442\u0432\u0438\u0435\u043c \u0432 \u043a\u0440\u043e\u0432\u0438 \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u0430 \u0430\u0443\u0442\u043e\u0430\u043d\u0442\u0438\u0442\u0435\u043b, \u043d\u0430\u043f\u0440\u0430\u0432\u043b\u0435\u043d\u043d\u044b\u0445 \u043f\u0440\u043e\u0442\u0438\u0432 FVIII (\u0438\u043d\u0433\u0438\u0431\u0438\u0442\u043e\u0440\u043e\u0432). \u041e\u043d\u043e \u043c\u043e\u0436\u0435\u0442 \u043d\u0430\u0431\u043b\u044e\u0434\u0430\u0442\u044c\u0441\u044f \u043a\u0430\u043a \u0443 \u043c\u0443\u0436\u0447\u0438\u043d, \u0442\u0430\u043a \u0438 \u0436\u0435\u043d\u0449\u0438\u043d, \u0447\u0430\u0449\u0435 \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0438\u0432\u0430\u0435\u0442\u0441\u044f \u0432 \u0441\u0440\u0435\u0434\u043d\u0435\u043c \u0432\u043e\u0437\u0440\u0430\u0441\u0442\u0435, \u043f\u0440\u043e\u044f\u0432\u043b\u044f\u0435\u0442\u0441\u044f \u0442\u044f\u0436\u0435\u043b\u044b\u043c\u0438 \u043a\u0440\u043e\u0432\u043e\u0442\u0435\u0447\u0435\u043d\u0438\u044f\u043c\u0438. \u0412 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u0445 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f\u0445 \u0431\u044b\u043b\u0430 \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0435\u043d\u0430 \u0430\u0441\u0441\u043e\u0446\u0438\u0430\u0446\u0438\u044f \u044d\u0442\u043e\u0433\u043e \u0441\u043e\u0441\u0442\u043e\u044f\u043d\u0438\u044f \u0441 \u0434\u0440\u0443\u0433\u0438\u043c\u0438 \u0430\u0443\u0442\u043e\u0438\u043c\u043c\u0443\u043d\u043d\u044b\u043c\u0438 \u0440\u0430\u0441\u0441\u0442\u0440\u043e\u0439\u0441\u0442\u0432\u0430\u043c\u0438 (\u0441\u0438\u0441\u0442\u0435\u043c\u043d\u0430\u044f \u043a\u0440\u0430\u0441\u043d\u0430\u044f \u0432\u043e\u043b\u0447\u0430\u043d\u043a\u0430, \u0440\u0435\u0432\u043c\u0430\u0442\u043e\u0438\u0434\u043d\u044b\u0439 \u0430\u0440\u0442\u0440\u0438\u0442, \u043d\u0435\u0441\u043f\u0435\u0446\u0438\u0444\u0438\u0447\u0435\u0441\u043a\u0438\u0439 \u044f\u0437\u0432\u0435\u043d\u043d\u044b\u0439 \u043a\u043e\u043b\u0438\u0442 \u0438 \u0442. \u0434.), \u0437\u043b\u043e\u043a\u0430\u0447\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u044b\u043c\u0438 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f\u043c\u0438, \u043f\u0440\u0438\u043c\u0435\u043d\u0435\u043d\u0438\u0435\u043c \u043d\u0435\u043a\u043e\u0442\u043e\u0440\u044b\u0445 \u043b\u0435\u043a\u0430\u0440\u0441\u0442\u0432\u0435\u043d\u043d\u044b\u0445 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432, \u043f\u043e\u0441\u043b\u0435\u0440\u043e\u0434\u043e\u0432\u044b\u043c \u043f\u0435\u0440\u0438\u043e\u0434\u043e\u043c \u0438 \u043f\u0440\u043e\u0447. \u0423 \u0447\u0430\u0441\u0442\u0438 \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u043e\u0432 \u0441\u0432\u044f\u0437\u0430\u043d\u043d\u043e\u0439 \u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u0438 \u0432\u044b\u044f\u0432\u0438\u0442\u044c \u043d\u0435 \u0443\u0434\u0430\u0435\u0442\u0441\u044f. \u0410\u0443\u0442\u043e\u0430\u043d\u0442\u0438\u0442\u0435\u043b\u0430 \u043a \u0444\u0430\u043a\u0442\u043e\u0440\u0443 VIII \u2013 \u043d\u0430\u0438\u0431\u043e\u043b\u0435\u0435 \u0447\u0430\u0441\u0442\u043e \u0432\u0441\u0442\u0440\u0435\u0447\u0430\u044e\u0449\u0438\u0439\u0441\u044f \u0441\u043f\u0435\u0446\u0438\u0444\u0438\u0447\u0435\u0441\u043a\u0438\u0439 \u0438\u043d\u0433\u0438\u0431\u0438\u0442\u043e\u0440 \u0444\u0430\u043a\u0442\u043e\u0440\u043e\u0432 \u0441\u0432\u0435\u0440\u0442\u044b\u0432\u0430\u043d\u0438\u044f. \u041f\u043e\u044f\u0432\u043b\u0435\u043d\u0438\u0435 \u0438\u043d\u0433\u0438\u0431\u0438\u0442\u043e\u0440\u043e\u0432 \u043c\u043e\u0436\u0435\u0442 \u0431\u044b\u0442\u044c \u043e\u0431\u0443\u0441\u043b\u043e\u0432\u043b\u0435\u043d\u043e \u0442\u0430\u043a\u0436\u0435 \u0432\u044b\u0440\u0430\u0431\u043e\u0442\u043a\u043e\u0439 \u0430\u0443\u0442\u043e\u0430\u043d\u0442\u0438\u0442\u0435\u043b \u043f\u0440\u043e\u0442\u0438\u0432 \u044d\u043a\u0437\u043e\u0433\u0435\u043d\u043d\u043e\u0433\u043e FVIII, \u043a\u043e\u0442\u043e\u0440\u044b\u0439 \u043f\u0440\u0438\u043c\u0435\u043d\u044f\u044e\u0442 \u0434\u043b\u044f \u043b\u0435\u0447\u0435\u043d\u0438\u044f \u0433\u0435\u043c\u043e\u0444\u0438\u043b\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0440\u0430\u0441\u0441\u0442\u0440\u043e\u0439\u0441\u0442\u0432.<\/p>\n<p><strong>\u041f\u0440\u0430\u0432\u0438\u043b\u0430 \u043f\u043e\u0434\u0433\u043e\u0442\u043e\u0432\u043a\u0438 \u043a \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044e \u043a\u0440\u043e\u0432\u0438<\/strong><\/p>\n<ul>\n<li>\u0412\u0437\u044f\u0442\u0438\u0435 \u043a\u0440\u043e\u0432\u0438 \u043f\u0440\u0435\u0434\u043f\u043e\u0447\u0442\u0438\u0442\u0435\u043b\u044c\u043d\u043e \u043f\u0440\u043e\u0432\u043e\u0434\u0438\u0442\u044c \u0443\u0442\u0440\u043e\u043c \u043d\u0430\u0442\u043e\u0449\u0430\u043a, \u043f\u043e\u0441\u043b\u0435 8-14 \u0447\u0430\u0441\u043e\u0432 \u043d\u043e\u0447\u043d\u043e\u0433\u043e \u043f\u0435\u0440\u0438\u043e\u0434\u0430 \u0433\u043e\u043b\u043e\u0434\u0430\u043d\u0438\u044f (\u0432\u043e\u0434\u0443 \u043f\u0438\u0442\u044c \u043c\u043e\u0436\u043d\u043e), \u0434\u043e\u043f\u0443\u0441\u0442\u0438\u043c\u043e \u0434\u043d\u0435\u043c \u0447\u0435\u0440\u0435\u0437 4 \u0447\u0430\u0441\u0430 \u043f\u043e\u0441\u043b\u0435 \u043b\u0435\u0433\u043a\u043e\u0433\u043e \u043f\u0440\u0438\u0435\u043c\u0430 \u043f\u0438\u0449\u0438.<\/li>\n<li>\u041d\u0430\u043a\u0430\u043d\u0443\u043d\u0435 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\u0433\u0435\u043f\u0430\u0440\u0438\u043d\u0430.<\/li>\n<\/ul>","protected":false},"featured_media":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_brand":[],"product_cat":[951],"product_tag":[],"class_list":{"0":"post-10009","1":"product","2":"type-product","3":"status-publish","5":"product_cat-teste-de-hemostaza","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\/10009","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=10009"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=10009"}],"wp:term":[{"taxonomy":"product_brand","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_brand?post=10009"},{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_cat?post=10009"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_tag?post=10009"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}