Введение. К числу безусловных наследственных детерминант тромбофилии относятся мутации в генах факторов II (G20210A) и V (G1691A). Однако их наличие, особенно в гетерозиготной форме, не всегда приводит к развитию тромботических осложнений, что свидетельствует о целесообразности поиска новых объективных методов выявления протромботического фенотипа у носителей рассматриваемых мутаций. Тест генерации тромбина (ТГТ) отражает состояние гемостаза индивидуума в совокупности взаимодействия прокоагулянтных и антикоагулянтных механизмов и позволяет эффективно выявлять гиперкоагуляцию. Цель исследования: установить целесообразность использования ТГТ для оценки гемостатического потенциала у асимптомных носителей мутаций в генах фактора V (G1691A) и/или протромбина (G20210A). Материалы и методы. Обследовано 42 асимптомных носителя мутации FV G1691A и/или FII G20210A (14 мужчин и 28 женщин, средний возраст — 37,0 ± 15,0 лет). Постановка ТГТ выполнялась в бедной тромбоцитами плазме. В тромбинограмме оценивали следующие показатели: PT (Peak thrombin — максимальное количество тромбина, образующегося в образце), ETP (endogenous thrombin potential — эндогенный тромбиновый потенциал), Lag-time — время инициации свёртывания и V (скорость образования тромбина). Результаты. Согласно полученным данным, гетерозиготное носительство мутаций FV G1691A и/или FII G20210A может ассоциироваться как с протромботическим, так и с нормальным фенотипом. У асимптомных носителей Лейденской мутации повышенные значения ЕТР и РТ обнаружены в 44% случаев, в то время как резистентность к активированному протеину С — в 67%. У большей части носителей мутации в гене протромбина отмечены превышающие норму значения ЕТР и РТ (71% и 57% случаев, соответственно). Скорость генерации тромбина превышала нормальные величины у 57% носителей мутации FV G1691A и у 64% носителей мутации FII G20210A. Значительную часть обследованных можно охарактеризовать как имеющих промежуточный протромботический фенотип, учитывая наличие у них одновременно как нормальных, так и патологических показателей ТГТ. Заключение. ТГТ является перспективным методом в плане создания индивидуального профиля риска для асимптомных носителей мутаций, ассоциированных с наследственной тромбофилией. Introduction. Mutations in genes of factors II (G20210A) and V (G1691A) are well known determinants of hereditary thrombophilia, but their presence, especially in the heterozygous form, does not always lead to the development of thrombotic complications.This indicates the importance of objective methods for the detection of prothrombotic phenotype in carriers of these mutations. Thrombin generation test (TGT) demonstrates the state of individual’s hemostasis in the interaction of procoagulant and anticoagulant mechanisms and allows to detect the hypercoagulability. Aim: to assess the hemostatic potential in asymptomatic carriers of FV G1691A or/and FII G20210A mutations by TGT. Materials and methods. We examined 42 asymptomatic carriers of FV G1691A mutation and/or G20210A prothrombin gene mutation (14 men and 28 women, average age — 37,0 ± 15,0 years). TGT was performed in platelet-poor plasma. In thrombinogram we assessed following parameters: PT (Peak thrombin is the maximum amount of thrombin formed in the sample), ETP (endogenous thrombin potential), Lag-time (coagulation initiation time) and V (thrombin generation rate). Results. According to data obtained, heterozygous carriage of FV G1691A and/or FII G20210A mutations can be associated with both prothrombotic and normal phenotypes. In asymptomatic carriers of Leiden mutation we revealed elevated values of ETP and RT in 44% of cases, while resistance to activated protein C — in 67%. The majority of FII G20210A mutation carriers demonstrated increased values of ETP and PT (71% and 57%, respectively). Thrombin generation rate exceeded normal values in 57% and 64% carriers of FV G1691A and FII G20210A mutations, respectively. The majority of examined patients can be characterized as having intermediate prothrombotic phenotype, taking into account that they had both normal and pathological values of TGT parameters. Conclusion. TGT is a perspective method for creating an individual risk profi le in asymptomatic carriers of mutations associatedwith hereditary thrombophilia.

Background. Thrombotic complications are one of the main problems of polycythemia vera (PV) treatment. They significantly impair the quality of life of these patients and may lead to the lethal outcome. A thrombotic event often precedes the diagnosis of this hematological disease. The pathogenesis of thrombosis in myeloproliferative neoplasms, PV, in particular, is a complex one. Prescription of antiaggregants in the absence of thrombosis and anticoagulants after a thrombotic event requires special attention and development of corresponding recommendations. The prescription of anticoagulants is impossible without taking into account the risks of hemorrhagic complications, which are also typical for myeloproliferative neoplasms. Aim. Assessment of the impact of hereditary thrombophilia genetic markers on the risk of thrombotic complications in patients with PV. Methods. The study examined 116 patients with PV, who were screened for markers of hereditary thrombophilia: factor V (G1691A, FV Leiden), prothrombin, methylene-tetrahydrofolate reductase (MTHFR), fibrinogen (F/), plasminogen activator inhibitor (PA/-1), and platelet fibrinogen receptor type ///A (GP///A). The incidence of these markers and their role in thrombosis in such patients was investigated. Results. The study provided data on the incidence of hereditary thrombophilia markers in patients with PV. Statistically significant differences in the incidence of these markers and homocysteine level were found between patients with thrombosis and without them. Conclusion. The information about the hereditary thrombophilia markers presence may be useful for the prescription of adequate antiaggregant and anticoagulant therapy for PV patients. Further research in this field is justified and it will probably demonstrate the relevance of hereditary thrombophilia markers as prognostic factors for thrombotic complications risk assessment.

Taking into account interrelations between inflammation and hemostasis, as well as immediate effects of IL-1β, IL-6 and TNFα upon blood coagulation system, one may suggest that their functional variantscould determine thrombosis risks both in arterial and venous circulation. The aim of this study was to assess possible role of allelic IL-1β, IL-6 and TNFα variants in pathogenesis of venous thromboembolism (VTE)in young patients. A retrospective analysis was performed for a group of 180 patients with early-onset VTE, and 150 healthy. In a sub-group with deep-vein thrombosis of lower extremities (DWTLE) complicated bypulmonary artery thromboembolia (PAT), we have revealed increased frequencies of IL-6 –174C homozygotes (30.8% vs 13.0%, p = 0.02) and IL-1β –31Т (61.5% vs 40.9%, p = 0.03), when compared with a subgroup of DWTLE. Among patients with “isolated” PAT a tendency for increased IL-1β –31ТТ ratio was found, as compared with DWTLE (53.8% vs 40.9%, р = 0,3), like as with control group (53.8% vs 40.7%, р = 0,3), These differences, however, were statistically insignificant. These data may suggest certain effects of IL-1β and IL-6 gene polymorphisms upon clinical characteristics of venous thromboembolism, rather than upon general VTE risk among young persons.

Combined hormonal contraceptives (CC) increase the risk of thrombotic complications. CC are known to induce prothrombotic changes in coagulation factors, data concerning the effect of CC on platelet haemostasis are limited. The aim of our study was to evaluate influence of non-oral and oral delivery of Ethinyl Estradiol (EE) and Dezogestrel on coagulation and platelet activation (shape change and number of platelets in aggregates).

Thalidomide and its analogs increase risk of venous thromboembolism (VTE) in patients with multiple myeloma (MM), particularly when used in combination with high-dose dexamatesone. It is important to choose proper thrombosis prophylaxis without increasing risk of bleeding. Our aim was to identify measurable factors associated with prothrombotic state in MM.