Введение. Рецидивирующие кровоизлияния в суставы у пациентов с болезнью Виллебранда (БВ) и гемофилией А (ГА) необратимо приводят к развитию деформирующей артропатии и хронического синовита. Прописанные в протоколе лечения больных гемофилией санаторно-курортное лечение, курсы лечебной физкультуры и физиотерапии сложно реализовать. Цель исследования: разработать и внедрить в клиническую практику Клиник ФГБОУ ВО СамГМУ Минздрава России программу реабилитации пациентов с наследственными коагулопатиями с суставным синдромом. Материалы и методы. В проспективном контролируемом наблюдательном рандомизированном исследовании приняли участие 5 пациентов с геморрагическими артропатиями. Из них 3 человека с диагнозом ГА и 2 пациента с диагнозом БВ типа 3. До начала курса восстановительного лечения и по его окончании проводили опрос всех пациентов, ангулометрию пораженных суставов, оценку движений в конечностях по шкале количественной оценки мышечной силы (англ. Medical Research Council Weakness Scale, MRC), оценку боли по визуально-аналоговой шкале (ВАШ), оценку независимости по шкале Рэнкина (англ. Rankin scale, RS), состояния тревожности с помощью госпитальной шкалы тревоги и депрессии (англ. Hospital Anxiety and Depression Scale, НАDS). Качество жизни оценивали по вопроснику EQ‑5D. Курс восстановительного лечения составлял 10 дней. Ежедневно пациенты получали процедуры лечебной гимнастики в зале и в бассейне, СРМ (англ. Continuous Passive Motion; непрерывное пассивное движение) терапию, тренировки на велотренажере, лазеротерапию, ультразвуковую терапию пораженных суставов. Результаты. После проведения комплексного восстановительного лечения у пациентов отмечали уменьшение боли и увеличение объема движений в суставе. Ограничение жизнедеятельности чаще оценивали как легкое. Однако пациенты по-прежнему отмечали субклинически выраженную тревогу и снижение качества жизни. Заключение. Пациентам с ГА и БВ, получающим фактор VIII свертывания крови, имеющим геморрагические артропатии, показана медицинская реабилитация в амбулаторных или стационарных условиях. Introduction. Recurrent hemorrhages in the joints in patients with Willebrand’s disease (BW) and hemophilia A (HA) irreversibly lead to the development of deforming arthropathy and chronic synovitis. It is difficult to implement sanatorium-resort treatment, physical therapy and physiotherapy courses prescribed in the protocol of treatment of patients with hemophilia. Objective: to develop and implement into clinical practice of Samara State Medical University Clinics a rehabilitation program for patients with hereditary coagulopathies and articular syndrome. Materials and Methods. The study involved 5 patients with hemorrhagic arthropathies. Of these, 3 people with a diagnosis of HA, and 2 patients with a diagnosis of type 3 BW. Before and after the course of rehabilitation treatment, all patients were interviewed, angulometry of the affected joints was performed, as well as the assessment of limb movements (according to Medical Research Council Weakness Scale, MRC), pain assessment (according to Visual Analogue Scale, VAS), assessment of independence (according to Rankin scale, RS), anxiety assessment (using Hospital Anxiety and Depression Scale, HADS). The quality of life was assessed using the EQ‑5D questionnaire. The course of rehabilitation treatment was 10 days. Every day, patients received therapeutic gymnastics procedures in the gym and in the pool, CPM (continuous passive motion) therapy, exercise bike training, laser therapy, ultrasound therapy of affected joints. Results. After comprehensive rehabilitation treatment, patients noted a decrease in pain and an increase in the volume of movements in the joint. Disability was more often assessed as mild. However, patients still noted subclinically expressed anxiety and a decrease in quality of life. Conclusion. Thus, patients with HA and BW receiving blood clotting factor VIII, having hemorrhagic arthropathies, are shown medical rehabilitation in outpatient or inpatient conditions.

Цель исследования: сбор и анализ данных о результатах применения нонакога альфа (Иннонафактор) при лечении больных с тяжелой и среднетяжелой формой гемофилии B в возрасте от 12 лет и старше в условиях рутинной клинической практики. Материалы и методы. В проспективное многоцентровое открытое наблюдательное исследование был включен 51 пациент в возрасте от 16 до 59 (32,9 ± 9,5) лет. Среди них было 39 (76,5%) пациентов с тяжелой формой и 12 (23,5%) пациентов со среднетяжелой формой гемофилии В. Эффективность лечения оценивали по числу спонтанных кровотечений, возникших в течение 72–96 ч после введения нонакога альфа, их степени тяжести и числу инъекций для купирования одного эпизода кровотечения. Безопасность оценивали по частоте и характеру нежелательных явлений (НЯ). Результаты. В группепациентов, завершивших исследование по протоколу, зарегистрировано 41 (63%) спонтанное и 24 (37%) посттравматических кровотечения. Медиана (Ме) числа спонтанных кровотечений в течение 72–96 ч после введения нонакога альфа была равна 2, межквартильный диапазон (англ. interquartile range, IQR) –6. Средняя профилактическая доза составила 28,25 ± 12,24 МЕ/кг (Me = 26,3 МЕ/кг; IQR = 24,4 МЕ/кг). Для купирования возникших кровотечений на фоне профилактического лечения требовалось в среднем 1,9 ± 1,8 введения в средней разовой дозе 2137 ± 790 МЕ (Me = 2000 МЕ; IQR = 1000 МЕ). По результатам оценки реакции на лечение острого гемартроза по шкале Всемирной федерации гемофилии (англ. World Federation of Hemophilia, WFH) в группе профилактического лечения в 16 (32,0%) эпизодах реакция была оценена как «отличная», в 31 (62,0%) эпизоде — как «хорошая» и в 3 (6,0%) эпизодах – как «умеренная». В группе лечения по требованию в 10 (100%) эпизодах реакция была оценена как «хорошая». Было зарегистрировано 26 НЯ у 14 пациентов, из которых только 2 НЯ (дисгевзия и кашель) у одного пациента имели связь с применением нонакога альфа. Заключение. Полученные результаты свидетельствуют об эффективности и безопасности нонакога альфа как для профилактического лечения, так и для купирования возникших кровотечений у обследованных пациентов с тяжелой и среднетяжелой формой гемофилии B в условиях рутинной клинической практики. Objectives: to analyze the results of the nonacog alfa (Innonafactor) use in patients aged 12 years and older with severe and moderate hemophilia B in routine clinical practice. Patients/Methods. A prospective multicenter open, observational study included 51 patients aged 16 to 59 (32.9 ± 9.5) years. Among them 39 (76.5%) patients had severe hemophilia B and 12 (23.5%) patients had moderate hemophilia B. Treatment efficacy was assessed by the number of spontaneous bleedings occurring within72–96 hours after nonacog alfa administration, bleeding severity and number of injections to stop one bleeding episode. Safety was assessed by the frequency and type of adverse events (AEs). Results. Forty one (63%) spontaneous and 24 (37%) post-traumatic bleedings were registered in patients completed the study according to protocol. The spontaneous bleedings incidence was 2 (Me; IQR = 6) within 72–96 hours after nonacog alfa administration. The mean prophylactic dose was 28.25 ± 12.24 IU/kg (Me = 26.3 IU/kg; IQR = 24.4 IU/kg). About 1.9 ± 1.8 injections were required to stop a bleeding appeared during prophylactic treatment, an average single dose was of 2137 ± 790 IU (Me = 2000 IU; IQR = 1000 IU). Basing on World Federation of Hemophilia (WFH) scale the response to treatment of acute hemarthrosis was considered as “excellent” in 16 (32.0%), “good” in 31 (62.0%), and “moderate” in 3 (6.0%) for patients with prophylactic treatment, and as “good” in 10 (100%) in the on-demand treated group. AEs incidence was as 26 in 14 patients, of which only patient performed 2 AEs (dysgeusia and cough) associated directly with the nonacog alfa administration. Conclusions. The results lets know nonacog alfa as effective and safe for prevention and to stop bleedings in patients with severe and moderate hemophilia B in routine clinical practice.

The aim of the study was to evaluate the efficacy, safety and pharmacokinetics of nonacog alfa (Innonafactor) in children aged 2 to 12 years with hemophilia B. Materials and methods: 15 patients (7.7±2.5 years ) were included in an open, multicenter, prospective, non-comparative clinical trial, of whom 12 were aged 6 to 12 years and 3 were aged 2 to 6 years. The efficacy of the drug was assessed against the background of the introduction of 45±10 IU/kg 2 times a week with an interval of 72–96 hours, the safety was assessed by the frequency and nature of adverse reactions. Results: 5 (22%) spontaneous and 18 (78%) post-traumatic bleedings were registered. The mean number of spontaneous bleeding within 72 hours after administration of nonacog alfa was 2±1.4. The average prophylactic dose was 47.74±6.47 IU/kg (Me 48.2 IU/kg). An average of 2.2±2.1 injections was required to stop a bleeding episode. 19 adverse events have been reported that are not related to nonacog alfa. Conclusion: the obtained data indicate the efficacy and safety of nonacog alfa in the study group of patients. Thus, the data obtained indicate the efficacy and safety of Innonafactor drug both for prophylactic treatment and for the relief of bleeding in patients aged 2 to 12 years with severe and moderate hemophilia B.

Введение. Гематогенная тромбофилия служит дополнительным фактором риска нарушений мозгового кровообращения (НМК). Цель исследования: изучить влияние повышенного уровня фактора VIII и нарушений в системе фибринолиза на НМК у пациентов с сочетанной патологией системы свертывания крови. Материалы и методы. Обследовано 20 пациентов с перенесенными ишемическими инсультами в возрасте от 36 до 56 лет. Определяли показатели плазменного, тромбоцитарного звеньев гемостаза, системы фибринолиза, а также генетические полиморфизмы системы гемостаза. Результаты. У всех пациентов выявлены различные сочетания генетических полиморфизмов, связанных с изменениями антикоагулянтного звена гемостаза, а также дефекты системы фибринолиза и коагуляционного звена гемостаза, что является дополнительным фактором риска НМК. Заключение. У пациентов молодого и среднего возраста, перенесших острое НМК по ишемическому типу, необходимо исследование системы свертывания крови, включающее определение содержания фактора VIII в крови, показателей системы фибринолиза и уровня гомоцистеина. Background. Hematogenous thrombophilia is an additional risk factor for cerebral circulatory disorders (ССD). Objectives: to study the impact of increased factor VIII level and disturbances of fibrinolysis system on ССD in patients with combined pathology of blood coagulation. Patients/Methods. We examined 20 patients with ischemic strokes aged from 36 to 56 years. The parameters of plasma hemostasis, platelet function, fibrinolysis system, as well as the genetic polymorphisms of hemostasis system were determined. Results. All patients had different combinations of genetic polymorphisms associated with anticoagulant hemostasis changes, as well as defects in fibrinolysis system and coagulation hemostasis that is an additional risk factor for ischemic stroke. Conclusions. In young and middle-aged patients with history of acute ischemic ССD, it is necessary to study blood coagulation, including the determination of blood factor VIII level, fibrinolysis system parameters and homocysteine content.

Currently, the main method of treatment for hemophilia A is replacement therapy with drugs of blood coagulation factors VIII (FVIII). As a result of the development of new production technologies, recombinant FVIII are increasingly used for the treatment of hemophilia A. The justification for the use of new drugs in pediatric clinical practice requires careful preparation and clinical research studies of their efficacy and safety. The aim of this study was to evaluate the efficacy, safety and pharmacokinetics (PK) of domestic B-domain deleted recombinant factor VIII of Moroctocog alpha (Octofactor, GENERIUM JSC) in a cohort of children with hemophilia A aged 6 to 12 years in the framework of phase III clinical study of moroktocoga alpha in children 2 to 12 years old with hemophilia A. Materials and methods of the research: the age cohort of 6 to 12 years olds of an open multicenter prospective noncomparative study included 27 male children with severe hemophilia A (mean age 8,3±1,9 years). The study was carried out sequentially in 2 stages. Stage I included the study of PK parameters in 22 patients after a single study drug dose of 50 IU/kg. At stage II, the efficacy and safety of the drug was assessed in patients of stage I, as well as in additionally included 5 patients who received the study drug dose of 30±10 IU/kg per day every 2–3 days for 22±1 weeks of treatment. To assess the efficacy, we analyzed the incidence of spontaneous bleeding that occurred within 48–72 h after drug administration; the number of injections and the dose of FVIII used for prophylaxis, as well as for treatment on demand of one episode of bleeding, taking into account its severity; number of patients with severe hemophilia A with residual FVIII activity >/=1% 48–72 h after drug administration; the investigator's overall assessment of response to therapy on the acute hemarthrosis response scale. The main indicators for the analysis of PK properties were the area under the «concentration-time» curve, the half-life, the elimination constant, the increase in activity, and the degree of recovery of activity. To assess safety, the frequency of formation of an inhibitor to FVIII, the dynamics of vital and laboratory parameters, the frequency and characteristics of adverse events (AEs) associated with the administration of the drug were taken into account. Results: the area under the FVIII-time activity curve in the region of 0–48 h (AUC0-48) and with exponential extrapolation to infinity (AUC0-inf) was 731,82±264,94%*h and 756,11±270,16%*h, respectively. The half-life (T1/2) was 10,32±2,27 hours. In the examined age group, 78 bleeding were recorded, of which only 27 (35%) were spontaneous, including 24 (30%) episodes that occurred during 48–72 hours after the administration of drug under investigation. Haemorrhage within 48–72 hours after administration of the Octofactor drug was absent or was observed rarely (1–3 times) against the background of prophylactic treatment in most patients (88%), the median number of bleeding within 48–72 hours after administration of the study drug was 2 episodes per observation period. The proportion of spontaneous bleeding was the smallest in patients receiving a single prophylactic doses of the study drug 2000–3000 IU (7% of all bleeding), the largest proportion of spontaneous bleeding was observed in patients receiving a single prophylactic doses of the study drug 1000–2000 IU (70% of bleeding). The average single dose of Octofactor for preventive treatment was 1290,4±458,6 IU or 39,12±7,79 IU/kg, for on-demand treatment – 1641,7±722,4 IU per single injection. Of the 78 reported bleeding episodes, 68 (87%) required the study drug administration for relief, while the remaining 10 bleedings were selfcontained. On average, to stop bleeding, it took 1,5±0,8 injections of the drug on demand, median doses were 1 [1; 2], and average doses were 2434,3±1501,7 IU. During the study, 37 AEs were recorded in 15 (56%) patients. At the same time, 36 AEs (97%) were not associated with the drug under investigation, and one AE (allergic reaction), according to the researchers, was associated with the use of the drug. Thus, the analysis of data indicates the efficacy and safety of the Octofactor drug both the prophylactic treatment and treatment of on-demand bleeding in 6 to 12 year old patients with severe hemophilia A.

Болезнь Виллебранда (БВ) может представлять определенные трудности у рожениц с данной патологией. Приведены 2 клинических примера использования у женщин с БВ фактора VIII свертывания крови с фактором Виллебранда, показана эффективность и безопасность их применения. У одной пациентки было также показано использование фактора свертывания крови VIII с фактором Виллебранда во время экстракорпорального оплодотворения. Von Willebrand disease presents a certain hemostatic problem among parturients. This article shows the effectiveness and safety of using coagulation factor VIII with von Willebrand factor for the prevention of bleeding in childbirth in 2 patients with type 3 von Willebrand disease. In one patient, the use of coagulation factor VIII with von Willebrand factor during in vitro fertilization was also shown.

Введение. Новая коронавирусная инфекция COVID-19 представляет повышенную опасность инфицирования у медицинских работников. Цель исследования: показать возможность применения дипиридамола у медицинских работников в комплексе мер первичной профилактики новой коронавирусной инфекции COVID-19. Материалы и методы. Наблюдались 33 медицинских работника: 14 человек принимали дипиридамол в дополнение к стандартным методам профилактики; 19 человек, не принимавшие дипиридамол, составили группу сравнения. Результаты. Несмотря на стандартные методы профилактики в многопрофильном стационаре, из 14 сотрудников, принимавших дипиридамол, 5 (35,7%) заболели коронавирусной инфекцией COVID-19 (подтвержденной); интерстициальная пневмония диагностирована у 4 человек. В группе из 19 сотрудников, не принимавших дипиридамол, заболели 13 (68,4%); интерстициальная пневмония была диагностирована у 11 человек. Заключение. Показана возможность применения дипиридамола в качестве дополнительного средства для снижения риска инфицирования новой коронавирусной инфекцией COVID-19. Background. Healthcare workers are under high risk of the novel coronavirus infection COVID-19. Objectives: to show the opportunity of dipyridamole using within the set of primary prophylaxis measures against the infection of COVID-19. Patients / Methods. We followed up 33 people from medical staff, of them 14 were taking dipyridamole in addition to standard prophylaxis methods; the comparison group consisted of 19 people who did not take dipyridamole. Results. Despite standard prophylaxis in a multidisciplinary hospital, out of 14 staff members who took dipyridamole, 5 (35.7%) catch coronavirus infection COVID-19 (justified); interstitial pneumonia was diagnosed in 4 people. In a group of 19 employees who did not take dipyridamole, 13 (68.4%) fell ill; interstitial pneumonia was diagnosed in 11 people. Conclusions. The opportunity of dipyridamole using has been shown as an additional means to reduce the risk to infect with COVID-19.

Providing hemophilia patients with blood coagulation preparations is one of the priority tasks of the national health care system. In 2011, the first recombinant factor IX was created in Russia (rFIX, nonacog alpha, Innonafactor, GENERIUM JSC), that was previously studied for pharmacokinetic (PK) parameters, efficacy and safety in adult patients and adolescents over 12 years of age with severe and moderate hemophilia B. Objective of this open-label, prospective, multicenter, noncomparative clinical study was to study PK, efficacy and safety of Innonafactor in 12 patients aged 6 to 12 years with severe and moderate forms of hemophilia B (FIX activity less than 2%). The study included periods of screening, studies of PK parameters and treatment within 26±1 weeks, but not less than 50 days of administration of the studied drug. Nonacog alfa was administered in the study of PK parameters at a dose of 75 IU/kg, once, for prophylactic treatment – at a dose of 45±10 IU/kg, 2 times a week with an interval of 72–96 h. 30 minutes after administration of the studied drug, FIX activity increased to 73,93±13,35%, with a gradual decrease to 5,88±1,97% 72 hours after administration. The area under the «concentration ‒ time» curve in the section 0–72 h (AUC0–72) and with exponential extrapolation to infinity (AUC00‒∞) was 1573,41±407,16%*h and 1808,74 ± 437,59%*h respectively. Biological half-life (T1/2) was 28,11±8,60 hours. During preventive treatment there were 19 hemorrhagic episodes, 14 (74%) bleedings were post-traumatic and 5 (26%) bleedings were spontaneous. Mean number of bleeding episodes over the entire observation period was 1,9±1,4. Mean number of episodes of spontaneous bleeding that occurred within 72 hours after Innonafactor administration in patients with bleeding was 2,5±2,1. During the entire study period, patients received 942,5 thousand IU of the drug Innonafactor, 890,5 thousand IU were administered for prophylaxis and 52 thousand IU to stop bleeding on demand. Mean single dose of Innonafactor for prophylactic treatment was 46,24±5,86 IU/kg, for on-demand treatment – 49±13,1 IU/kg. Of the 19 registered bleeding episodes, 14 (73.7%) episodes required the administration of the studied drug; 5 (26,3%) bleedings stopped on their own. To stop one episode of bleeding, an average of 2,3±2,3 administration of nonacog alfa was required. At the end of the study, the proportion of hemophilia B patients with residual FIX activity of 2% or more was 92%. During the study, 14 adverse events (AEs) were registered in 7 (58,3%) patients. All reported AEs were not study drug related and did not require study drug withdrawal. Thromboembolic complications and immunogenic reactions were not registered. Thus, the data obtained indicate efficacy and safety of Innafactor both for prophylactic treatment and for on-demand treatment of bleeding in patients aged 6 to 12 years with severe and moderate hemophilia B.

The article shows the possible use of sulodexidi in a patient with primary infertility of unknown origin associated with an excess of the plasminogen activator type 1 inhibitor. This method illustrates the possibility of pregnancy when taking sulodexidi at the stage of pregravidar preparation in a woman with hypofibrinolysis.

Введение. Новая коронавирусная инфекция COVID-19 представляет повышенную опасность инфицирования у медицинских работников. Цель исследования: показать возможность применения дипиридамола у медицинских работников в комплексе мер первичной профилактики новой коронавирусной инфекции COVID-19. Материалы и методы. Наблюдались 33 медицинских работника: 14 человек принимали дипиридамол в дополнение к стандартным методам профилактики; 19 человек, не принимавшие дипиридамол, составили группу сравнения. Результаты. Несмотря на стандартные методы профилактики в многопрофильном стационаре, из 14 сотрудников, принимавших дипиридамол, 5 (35,7%) заболели коронавирусной инфекцией COVID-19 (подтвержденной); интерстициальная пневмония диагностирована у 4 человек. В группе из 19 сотрудников, не принимавших дипиридамол, заболели 13 (68,4%); интерстициальная пневмония была диагностирована у 11 человек. Заключение. Показана возможность применения дипиридамола в качестве дополнительного средства для снижения риска инфицирования новой коронавирусной инфекцией COVID-19. Background. Healthcare workers are under high risk of the novel coronavirus infection COVID-19. Objectives: to show the opportunity of dipyridamole using within the set of primary prophylaxis measures against the infection of COVID-19. Patients / Methods. We followed up 33 people from medical staff, of them 14 were taking dipyridamole in addition to standard prophylaxis methods; the comparison group consisted of 19 people who did not take dipyridamole. Results. Despite standard prophylaxis in a multidisciplinary hospital, out of 14 staff members who took dipyridamole, 5 (35.7%) catch coronavirus infection COVID-19 (justified); interstitial pneumonia was diagnosed in 4 people. In a group of 19 employees who did not take dipyridamole, 13 (68.4%) fell ill; interstitial pneumonia was diagnosed in 11 people. Conclusions. The opportunity of dipyridamole using has been shown as an additional means to reduce the risk to infect with COVID-19.

Introduction. Frequent bleeding with hemophilia significantly worsens the quality of life of patients. The pathogenesis of hemorrhage in hemophilia has not been studied enough, especially at the vascular level, so it is necessary to study microcirculation in this disease. The purpose of the study is to assess the mechanisms of regulation of blood tissue perfusion and the adaptive reserves of the microcirculation system in patients with hemophilia. Materials and methods. Total microcirculation was assessed by laser Doppler flowmetry in 44 patients with hemophilia A between the ages of 14 and 20 years. Severe form of the disease was in 59 % of patients, the average – in 32 %, light – in 9 % of patients. The control group included 26 healthy men aged 14 to 19 years. The sensors recorded blood flow in the index fingers on both sides. In 20 patients with hemophilia А, an occlusion test was performed. The results of the study. In patients with hemophilia, asymmetric changes in microcirculation parameters were detected when measured in the area of the index fingers. At rest in patients with hemophilia, the prevalence of vasospasm was revealed: a decrease in the perfusion index M, an increased blood bypass due to the predominance of myogenic tone. However, neurogenic tone indicators tended to decrease. During occlusive ischemia, vasospasm is slowed down in the first seconds after the onset of exposure to the stress factor. Conclusion. The study revealed a dysregulation of the vascular tone of the microvasculature in young hemophilia patients at rest and under the influence of a stress factor in the form of short-term ischemia. Therefore, with hemophilia from a young age, control of microcirculation is necessary for the timely prevention of both bleeding and cardiovascular pathology associated with vasospasm.

Relevance. In accordance with the guidelines on the clinical investigation of clotting factor VIII products of the European Medicines Agency and guidelines on pharmacovigilance of the Eurasian Economic Union, after registration of a new drug, it is recommended to study its efficacy and safety on a large population of patients in a standard medical practice to clarify and identify new data.Materials and methods. In a prospective, multicenter, open-label, uncontrolled observational study, the efficacy and safety of the domestic recombinant B-domain deleted blood clotting factor FVIII (FVIII) (moroctocog alfa, Octofactor®, JSC “GENERIUM”) in patients with moderate and severe hemophilia A in the context of standard medical practice (study protocol number CI-51/15). Patients received the drug in terms of standard medical practice for the purpose of prophylactic treatment or on demand treatment. For prophylactic treatment Octofactor was administered to patients according to the instructions for medical use in a single dose of 20–40 IU/kg every 2–3 days. In the case of bleeding a single dose of Octofactor was calculated taking into account the severity and localization of bleeding in accordance with the instructions for medical use. The results of the treatment were analyzed for a period of 52 ± 2 weeks. The main parameter for evaluating the efficacy was the frequency of spontaneous bleeding that occurred within 48–72 hours after the administration of the Octofactor. Additional parameters for evaluating the efficacy included: the severity of spontaneous bleeding arising during the prophylactic treatment; the number of injections and the total dose of the Octofactor to stop 1 episode of bleeding; the amount of Octofactor used during the entire observation period (52 ± 2 weeks) and for 1 month both for prophylaxis and for stopping the bleeding that occurred; an indicator of the efficacy of therapy on the scale for determining the response to treatment of acute hemarthrosis (World Federation of Hemophilia, WFH).Results.According to the results of the screening survey 237 male patients aged from 19 to 78 years old (mean age 35.2 ± 11.1 years) with moderate and severe hemophilia A (FAS-population) were included in the study. The efficacy of therapy was evaluated in 202 patients who underwent all the planned procedures during the observation period (PP-population). 193 (95.5 %) patients received prophylactic treatment, 9 (4.5 %) patients received on-demand treatment. Evaluation of the efficacy of treatment was carried out on the basis of basic and additional parameters. The main parameter for evaluating the efficacy – the frequency of spontaneous bleeding that occurred within 48–72 hours after the administration of the Octofactor – was 52 ± 2 weeks within 1.4 ± 2.9 cases. At the same time, the proportion of spontaneous bleeding that occurred within 48–72 hours after administration of the Octofactor preparation was 45.2 % of the total number of spontaneous bleeding and 15.6 % of the total number of all bleeding in patients who received prophylactic treatment. Among 608 spontaneous bleeding that occurred in patients receiving prophylactic treatment, 287 (47.2 %) of the bleeding were mild, 289 (47.5 %) were moderate and 32 (5.3 %) were heavy. Of the 275 spontaneous bleeding that occurred within 48–72 hours after administration of the study drug for prophylactic purposes, 117 (42.5 %) episodes were mild, 146 (53.1 %) were moderate, and 12 (4.4 %) were severe. With prophylactic administration the average single dose of the Octofactor was 2036.3 ± 884.7 IU, or 27.3 ± 11.2 IU/kg, in the treatment of bleeding occured during prophylactic treatment – 2227.7 ± 1087 IU, in the treatment of bleeding in patients receiving the drug only on demand – 2280.7 ± 1037.2 IU. The average monthly intake of the drug by one patient in prophylactic treatment was 19.75 ± 9.75 thousand IU, while the average monthly consumption of the drug for preventing bleeding from one patient was 17.16 ± 9.13 thousand IU for stopping bleeding against the background prevention – 3.87 ± 3.97 thousand IU. One patient who received on-demand treatment had an average monthly average of 13.47 ± 13.46 thousand IU of the Octofactor preparation. For stopping 1 bleeding, on average, 1.7 ± 1.7 injections of the Octofactor preparation were required, in the prophylactic treatment group – 1.8 ± 1.8, and in the on-demand treatment group – 1.5 ± 1.1. In the overwhelming majority of cases, patients of both groups showed excellent and good response to all treatment of acute hemarthrosis on the scale of the WFH on all visits, the reaction was moderate in a few episodes, and only in 1 case of acute hemarthrosis there was no response to the drug administration. The safety of therapy was evaluated in 228 patients who received at least 1 Octofactor administration during the study (mITT-population). There were 66 adverse events in 40 patients, 10 of them were associated with the use of the drug, the most significant of which were the formation of inhibiting antibodies to FVIII in low titer (1.5 U) in 1 patient and the development of allergic reactions in 2 patients.Conclusions.Under the conditions of standard medical practice the efficacy and safety of Octofactor was confirmed for both prophylactic treatment and on-demand bleeding treatment in adult patients with severe and moderate hemophilia A.

Objectives - the review presents the analysis of the main changes in Rome IV. The subsequent Rome IV consensus focused on the etiology, pathogenesis, diagnosis and differential diagnosis of the functional gastrointestinal disorders. It updated some definitions of the functional gastrointestinal disorders; opioid-induced constipation was set as a separate disorder; functional abdominal distention was considered specific for functional abdominal bloating as both disorders are often combined and do not replace each other. The functional gastrointestinal disorders still remain of the high medico-social importance as they are endemic, refractory and cause long-term disability.

Relevance.The development of a new recombinant blood coagulation factor VIII preparation is a promising step towards optimizing the treatment of hemophilia A. An introduction of a new medication into clinical practice precedes a clinical trials to evaluate the efficacy and safety.Materials and methods.The efficacy and safety of the domestic recombinant B-domain deleted blood coagulation factor VIII (FVIII) (moroctocog alfa, Octofactor®, JSC “GENERIUM”) were studied in the preventive treatment of 31 patients aged 21 to 52 years with severe haemophilia A. The Octofactor was administered in doses of 40 ± 5 IU/kg 3 times per week at intervals of at least 48 hours for 21 ± 1 weeks.Results.The efficacy of therapy was evaluated in 30 patients, since 1 patient refused to participate in the trial after the first injection of the study medication. There were registered 43 episodes of bleeding among 11 patients in the course of the preventive treatment with Octofactor. The average number of bleeding episodes was 1.4 ± 2.58. There were 43 bleeding episodes, 9 (20.9 %) of them were posttraumatic, 34 (79.1 %) of them were spontaneous. The average number of the spontaneous bleeding episodes (a major criterion of the efficacy) was 1.13 ± 2.19, which showed a low incidence of exacerbations of the hemorrhagic syndrome in the course of preventive treatment with Octofactor. Among all registered bleeding episodes there were 6 (14 %) mild episodes, 37 (86 %) moderate episodes. Among all spontaneous bleedings there were 6 mild episodes (17.6 %), 28 (82.4 %) moderate episodes. All posttraumatic bleedings were moderate. The vast majority (36, or 83.7 %) of bleeding episodes were stopped with administration of the Octofactor. The average number of administrations of the Octofactor for arresting 1 bleeding episode was 1.2 ± 0.56, for 1 spontaneous bleeding episode – 1.2 ± 0.59. On average, it was required to administer 3534.9 ± 2329.02 IU of the Octofactor to stop 1 episode of bleeding. In the vast majority of patients with severe hemophilia A (83.3–86.7 %), the remaining activity FVIII was 1 % or more after the administration of the Octofactor in 48 hours. The total amount of the Octofactor, introduced for the prevention of bleeding, was 6,107,000 IU, to stop bleeding – 152,000 IU. The safety of therapy was evaluated in 31 patients. There were recorded 25 adverse events (AE) in 17 patients. Among them the laboratory ones prevailed in 23 (92 %) cases, which is not associated with the use of the trial medication. There were noted nausea and an unpleasant aftertaste in the mouth in 1 patient during the first administration of the Octofactor, and therefore he refused to continue to participate in the trial. Causality 2 AE with the study drug was regarded as definite. Such AE are expected and described in the instructions to the preparation. All AE were not serious and mild and resolved without outcomes. There were no presented thromboembolic events and immunogenic reactions.Conclusions.The obtained data testify to the efficacy and safety of the Octofactor both for preventive measures and for stopping bleeding in adult patients with severe hemophilia A.

The article presents the historical and modern conception of therapeutic liver diseases, which have eponymicnames. Five liver diseases with an eponymic history are considered: Addison-Gall's syndrome (primary biliary cirrhosis), Badd-Chiari syndrome, Bearn-Kunkel syndrome (autoimmune hepatitis), Wilson-Konovalov's disease and Gilbert’s syndrome. The discovery of these diseases and the development of hepatology as a science are closely related tothose scientists whose names were subsequently given to these diseases. The review presents a historical background aswell as current information on epidemiology, etiology, developmental mechanisms, diagnosis, differential diagnosis and treatment of the above mentioned syndroms, which can be recommended for physicians, gastroenterologists and hepatologists

Результаты многоцентрового, проспективного, открытого, неконтролируемого исследования эффективности и безопасности препарата Иннонафактор у пациентов в возрасте 12 лет и старше с тяжелой и среднетяжелой гемофилией В

Aim of the review - to illuminate the problem of proton pump inhibitor(PPI)-refractory form of gastroesophageal reflux disease (RFGERD) at a modern scientific level. It is shown that PPI remain the standard and the most effective therapy for GERD. Patients, whose GERD symptoms are refractory to PPI, should be further examined to exclude other diseases. It is possible to use different treatment options: medication, endoscopic or surgical treatment. The response to IPP therapy can be complete (no symptoms), partial or absent. In patients with complete response to treatment with PPI no other therapy is provided. Currently, new methods of RFGERD treatment are being actively developed. Patients with partial response may require endoscopic or surgical intervention.

Хирургия 12, 2016 Тромбоз печеночных вен у мест их впадения в нижнюю полую вену описан английским врачом G. Budd в 1845 г. Позднее, в 1899 г., австрийский патолог Н. Chiari предоставил информацию о 13 случаях этого синдрома. Из-за редкости заболевания (1 на 100 000 населения в мире, 1 на 1 000 000 населения в Европе) в отечественной литературе обычно публикуются спорадические наблюдения [1]. Единой классификации не существует [2, 3]. Наиболее частой причиной развития заболевания являются врожденные и приобретенные нарушения гемостаза [4, 5]. Этим объясняется частое распространение тромбоза на воротную вену и ее притоки [6]. При отсутствии специфической терапии и оперативного лечения прогноз неблагоприятный. Больная К., 34 лет, была госпитализирована 01.12.13 в клинику Самарского государственного медицинского университета в экстренном порядке в тяжелом состоянии с жалобами на выраженную общую слабость, головокружение, увеличение живота, тошноту, рвоту 3—4 раза в день после еды, отеки нижних конечностей. За 3 мес до поступления — вторые роды в срок без осложнений. Больной себя считает в течение 1 мес. Находилась на лечении в хирургическом отделении одной из городских больниц с диагнозом: «острый панкреатит». В связи с развитием асцита, причина которого была неясна, направлена в наш медицинский центр. В ходе обследования выявлена тромбофилия с избытком VIII фактора и фактора Виллебранда. При КТ обнаружены полная окклюзия печеночных вен и субтотальная окклюзия нижней полой вены, резкое обеднение кровотока по правой ветви воротной вены. После обследования и предоперационной подготовки в течение 4 дней в ОРИТ 11.12 больная была оперирована (В.В. Сухоруков). Из трансъяремного доступа выполнена реканализация правой печеночной вены. Произведено трансъяремное внутрипеченочное портокавальное шунтирование (TIPSS). При прямой портографии (рис. 1, а) выявлены окклюзия селезеночной вены, левой ветви воротной вены, выраженная редукция кровотока в бассейне правой ветви воротной вены, ретроградный кровоток по кардиальным венам, врожденный портогеморроидальный анастомоз (см. рис. 1, б). Портометрия — 490 мм вод.ст. На баллоне Express LD Vascular (Abbott Vascular) последовательно имплантировано два периферических стента размером 10×57 мм от просвета устья правой ветви воротной вены до нижней полой вены (см. рис. 1, в). Портальное давление снизилось до 320 мм вод.ст. Достигнута редукция кровотока по кардиальным венам и портогеморроидальному анастомозу. Ранний послеоперационный период в условиях ОРИТ протекал стабильно. Диспепсические расстройства купированы, появился аппетит. Уменьшилось количество асцитического отделяемого. Кровоток по транспеченочному шунту ежедневно контролировали с помощью УЗИ в режиме цветового допплеровского картирования (ЦДК). Проводили коррекцию гиповолемии, антикоагулянтную, гепатопротекторную, антибактериальную терапию, нутритивную поддержку. Однако на 3-и сутки после операции отмечено нарастание асцита, появление тошноты и рвоты, гипотонии, нарастание тахикардии. При ЦДК обнаружен тромбоз портокавального шунта. По согласованию со специалистами Гематологического научного центра Минздрава РФ предпринята попытка консервативного лечения. С целью коррекции гемостаза ежедневно выполняли плазмаферез с забором 300—600 мл и возмещением адекватным объемом свежезамороженной плазмы. Проводили дозированную эвакуацию асцитической жидкости по 800—1000 мл/сут. Несмотря на это, состояние больной ухудшалось. Нарастала гиповолемия, сердечно-сосудистая, дыхательная недостаточность. Усиливался цитолиз. Потребовалась постоянная вазопрессорная поддержка. На 8-е сутки после первой операции (19.12) больная оперирована повторно (В.В. Сухоруков). Использован трансъяремный доступ. При кавографии обнаружен стеноз нижней полой вены, подтвержден тромбоз TIPSS (рис. 2). Шунт механически реканализирован. Портометрия — 350 мм вод.ст. При прямой портографии выявлены окклюзия селезеночной вены, тромбоз шунта на всем протяжении и проксимальной части воротной вены. Кровоток сохранен по портогеморроидальному анастомозу и кардиаль-