Relevance. Immune tolerance induction (ITI) is the only approach proven to eradicate inhibitors in hemophilia A patients. ITI with Octanate® (human VWF-stabilized FVIII) has been shown to be effective at eradicating inhibitors, even in poor-prognosis patients. Here we report interim data from two observational, prospective studies on the use of Octanate® for ITI in patients in Russia. Purposes of research. The primary objective was to assess the efficacy of ITI. Secondary objectives included assessment of time to ITI success and inhibitor eradication. Patients and methods. Patients of any age with any severity of hemophilia A and a FVIII inhibitor  0.6 BU/mL were eligible. The ITI regimen was at the discretion of the treating physician. Results. The analysis included 73 patients. ITI outcomes were assessed in 63 patients who had completed the study, of whom 56 (89 %) had  1 poor prognostic factors. Inhibitor eradication was achieved by 77.1 % (37/48) of primary ITI patients and 71.4 % (45/63) of all patients, in a median of 2.4 months (range – 0.0–27.4) for both groups. Complete success was achieved by 72.9 % (35/48) of primary ITI patients in a median of 8.9 months (range – 2.4–28.0) and 66.7 % (42/63) of all patients in a median of 10.5 months (range – 2.4–28.0). No relapses were reported after complete or partial ITI success. Of the patients with  1 poor prognostic factors, 67.9 % achieved inhibitor eradication and 62.5 % complete success. Conclusions. ITI with Octanate® in a real-world setting showed rapid and sustained success, even in patients with poor prognostic factors.

Введение. Тяжелые послеродовые кровотечения остаются одной из основных причин материнской смертности. Своевременная диагностика нарушений в системе гемостаза и целенаправленная гемостатическая терапия с включением концентратов факторов свертывания может способствовать уменьшению трансфузионной нагрузки и остановке кровотечения. Цель исследования: оценить эффективность концентрата протромбинового комплекса (КПК) «Протромплекс 600» для лечения тяжелых послеродовых кровотечений. Материалы и методы. В исследование включены 44 женщины, которым вводили КПК в комплексной терапии тяжелых послеродовых кровотечений. Осуществляли контроль состояния гемостаза до и после введения препарата с помощью стандартных коагулологических тестов и тромбоэластографии (ТЭГ). Показания для введения КПК: тяжелое послеродовое кровотечение, гипокоагуляция по плазменному звену гемостаза, по данным ТЭГ, увеличение международного нормализованного отношения ≥ 1,5. Результаты. Замедление темпа кровотечения с последующей остановкой достигнута у 38 (86%) рожениц после однократного введения КПК в дозе 10–25 МЕ/кг. Не зафиксировано каких-либо побочных реакций на введение препарата, в том числе тромбогенных осложнений. Уровень антитромбина III у пациенток после инфузии «Протромплекса» не выходил за рамки референсных значений. Заключение. Хороший терапевтический эффект КПК у данной категории больных подтверждает клиническую целесообразность и патогенетическую обоснованность его введения для быстрой коррекции дефицита основных факторов свертывания. Introduction. Severe postpartum hemorrhage remains one of the main causes of maternal mortality. In-time diagnosis of coagulation disorders and targeted therapy, with incorporation of coagulation’s factor concentrates, can help reduce blood components consumption and stop bleeding. Aim: to assess the eff ectiveness of prothrombin complex concentrate (PCC) «Protromplex 600» for treatment of severe postpartum hemorrhage. Materials and methods. PCC was used in complex therapy of severe postpartum hemorrhage in 44 women. Hemostasis was monitored before and after PCC administration using standard coagulological tests and thromboelastography (TEG). Indications for PCC administration: severe postpartum hemorrhage, hypocoagulation in plasma hemostasis link, hypocoagulation according to TEG, increased international normalized ratio ≥ 1.5. Results. Decreasing of bleeding rate with its subsequent stopping was achieved in 38 (86%) post-delivery women after single PCC administration at dose 10–25 IU/kg. No adverse reactions to PCC administration, including thrombogenic complications were fi xed. After «Protromplex 600» infusion antithrombin III level was within the reference values. Conclusion. A good therapeutic effect of CCP in this category of patients confirms the clinical advisability and pathogenetic validity of its administration for the rapid correction major coagulation factors deficiency.

Introduction . The Problem of the use of recombinant activated factor VII (rFVIIa) in hemophilia patients with inhibitors is the complexity of the laboratory evaluation of the therapy. After rFVIIa  administration standard clothing tests are changing, however, are not normalized. The aim of this study was to investigate the possibility of using standard clothing tests (activated partial thromboplastin time (APTT) and prothrombin time (PT)) to assess the efficiency of hemostatic  therapy with rFVIIa in hemophilia patients with inhibitors. The aim of this work is to investigate the possibility of using standard clothing  tests (activated partial thromboplastin time (APTT), prothrombin time (PT)) to assess the efficiency of hemostatic  therapy with rFVIIa in patients with inhibitory hemophilia. Materials and methods. 20 male hemophilia patients with inhibitors were included in the study. At the time of study inclusion  none patients had signs of bleeding. Plasma levels of FVIII were < 1  %, FVIII inhibitor titers were from 5 BU/ml to 463 BU/ml. All  patients received rFVIIa (Coagil-VII) at a dose of 90 μg/kg. Before  the administration of rFVIIa and then in 15, 30 and 60 min, 2 and 24 h the APTT, the PT, the endogenous thrombin potential (ETP) and thromboelastography (TEG) parameters (reaction time – R, maximum amplitude – MA) were evaluated. Results. Before rFVIIa administration all patients had prolonged APTT. 15 min after administration of rFVIIa APTT shortened and remained shorter than baseline level, but 2 times longer than  normal ranges during 2 hours. The PT also significantly decreased in  15 min after the rFVIIa administration. Prior to treatment patients had minimal to no clotting detectable by TEG. Administration of rFVIIa led to normalization of TEG traces in the most of the patients  in 15 min. Elevated by TEG hemostatic effects persisted for 2 h. The  ETP increased in 15 min after rFVIIa administration. This increase of  ETP persisted for 60 min. There were strong correlations between R  and APTT (r = 0.74; p = 0.001), between MA and APTT (r = 0.70),  between PT and R (r = 0.79; p = 0.01), PT and MA (r = 0.76; p =  0.01). There were no correlations between ETP and APTT, and  between ETP and R. The shortening of the APTT after rFVIIa administration for 17 s and more or for 22 % and more from the baseline levels were associated with the normalization of R and MA.  Changes of the PT poorly allowed to discriminate normal values of  TEG. Conclusion . Shortening of the APTT after rFVIIa administration in hemophilia patients with inhibitor for 17 s and more or for 22 % and more from the initial value can be used to assess the hemostatic efficiency of rFVIIa therapy.

The liver function was studied in 135 patients with severe hemophilia A and B. It has been established that in hemophilia the liver is naturally involved into the pathological process. The liver function disorders are manifested as inflammatory and cytolytic syndromes. The incidence rate and degree of the shifts manifestation correlate with the disease duration.