Despite availability of prophylactic therapy for hemophilia A with factor VIII concentrates with a standard half-life, patients continue to experience episodes of bleeding and joint damage. The reasons for this may be the relatively short half-life of the factor VIII drug and the low adherence of patients to treatment. The appearance of clotting factor concentrates with an extended half-life makes it possible to reduce the frequency of infusions and increase the residual activity of the deficient factor. The article presents clinical observations of the use of Efmoroctocog alfa (recombinant human coagulation factor VIII, Fc fusion protein (rFVIIIFc)) in a 16-year-old adolescent and a 7-year-old child with severe and moderate forms of hemophilia A. In order to select the most rational therapy regimen and evaluate the effectiveness of treatment, the authors have conducted individual assessments of patients’ pharmacokinetic (PK) parameters. The drug administration in both patients was twice per week. To assess individual PK, the WAPPS-Hemo was used in order to calculate individual PK parameters based on a small plasma samples collected during routine prophylactic treatment. During the PK study, 3 blood samples were taken to determine the level of factor VIII in a one-step method. In a 16-year-old patient, the half-life of Efmoroctocog alfa (t1/2) was 24.25 hours. The activity of factor VIII prior to the next injection was 7.4%. In addition, 81% of time the factor VIII activity was above 15%. In a 7-year-old patient, the t1/2 of the drug was 12.75 hours. The minimum residual activity of factor VIII was 2.1%, 86% of time the activity of factor VIII was above 3%. Conclusion: high efficacy and safety were demonstrated based on the results of the use of Efmoroctocog alfa in routine clinical practice in previously treated pediatric and adolescent patients with severe and moderate hemophilia A, as well as the reduction in the frequency of infusions per week from 3 to 2.

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Введение. Гемофилия А (ГФА) — сцепленное с Х-хромосомой рецессивное врожденное заболевание, обусловленное недостаточностью VIII фактора свертывания крови (FVIII). Главным признаком заболевания является склонность к кровотечениям. Клинические проявления ГФА, как правило, коррелируют с уровнем активности FVIII. Единственным эффективным лечением гемофилии в настоящее время является заместительная терапия препаратами дефицитного фактора. Материалы и методы. Проведен ретроспективный анализ результатов обследования 28 пациентов (14 детей в возрасте от 3 до 17 лет и 14 взрослых в возрасте от 21 до 57 лет) с тяжелой формой ГФА. Все пациенты находились на длительной профилактической терапии препаратами FVIII — как рекомбинантными, так и плазматическими. Для подбора оптимального режима профилактики пациенту с ГФА проводили тест восстановления (in vivo recovery) — определение активности FVIII в двух пробах крови; определяли также прирост показателя восстановления (incremental recovery), активированное частичное тромбопластиновое время и каолиновое время. Результаты. Проведена оценка теста восстановления фактора свертывания VIII при применении плазматических и рекомбинантного препаратов фактора VIII у пациентов с тяжелой гемофилией А; изучена корреляция теста восстановления с фармакодинамическими показателями, характеризующими состояние коагуляции. Заключение. Ввиду наличия внутрииндивидуальных и межиндивидуальных колебаний фармакокинетических показателей препаратов фактора свертывания VIII у пациентов с ГФА рекомендуется проведение теста восстановления как при назначении препарата фактора свертывания VIII, так и в процессе длительной профилактики с целью контроля за терапией и ее оптимизации в случае необходимости. Introduction. Hemophilia A (HРA) is a recessive X-linked congenital disease caused by the defi ciency of VIII coagulation factor (FVIII). Hemorrhagic tendency is the main sign of the disease. As a rule, clinical manifestations of HPA correlate with level of FVIII activity. At present time substitution therapy with medication of defi cit factor is the only eff ective treatment for hemophilia. Materials and methods. We performed a retrospective study analysis of 28 patients (14 children aged from 3 to 17 years and 14 adults aged from 21 to 57 years) examination with severe HРA. All patients received prolonged preventive therapy with recombinant factor VIII products. To select the optimal prophylaxis mode for patients with HPA we performed a recovery test (in vivo recovery), determination of FVIII activity in two blood samples, determined index of incremental recovery, activated partial thromboplastin time and kaolin time. Results. We assessed recovery test for coagulation factor VIII using plasma and recombinant factor VIII products in patients with severe haemophilia A and studied correlation of recovery test with pharmacodynamic parameters that characterized coagulation state. Conclusion. Due to intra-individual and inter-individual fl uctuations in pharmacokinetic parameters of recombinant factor VIII products in patients with HPA we recommend to perform a recovery test both at appointment of coagulation factor VIII product and also during of long-term prophylaxis for monitoring and optimization of therapy.