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.

Молекулярно-генетический фенотип (носительство одной из мутаций JAK2V617F (JAK2+), MPL (MPL+), CALR (CALR1+-1-й тип, CALR2+-2-й тип), его отсутствие-тройной-негативный (ТН) статус при эссенциальной тромбоцитемии (ЭТ) рассматриваются в качестве фактора, влияющего на развитие тромбогеморрагических осложнений. Цель исследования-оценить наличие и характер взаимосвязей между молекулярно-генетическими нарушениями, клинико-лабораторными параметрами и развитием осложнений, прогнозом течения ЭТ. Методы. Проанализированы данные, полученные на этапе диагностики и последующего динамического наблюдения за 240 пациентами с ЭТ (критерии ВОЗ 2008 г.). Исследовались показатели гемограммы, результаты молекулярно-генетических методов: полиморфизма длин рестрикционных фрагментов (ПДРФ) для определения мутации JAK2V617F, полимеразной цепной реакции с последующим анализом ПДРФ (ПЦР-ПДРФ) для выявления мутаций MPL и прямого секвенирования для обнаружения CALR. Регистрировались тромботические и / или геморрагические осложнения: артериальные / венозные тромбозы, острый инфаркт миокарда (ОИМ), острое нарушение мозгового кровообращения (ОНМК) и кровотечения. Проведен анализ общей выживаемости (ОВ) у пациентов с наличием / отсутствием осложнений, различных групп риска развития тромботических осложнений по шкале риска тромбозов при ЭТ (ВОЗ-ЭТ IPSET-thrombosis).

Background & Aims. The presence of different molecular genetic markers of clonality (mutations in JAK2, MPL, CALR) or their absence (triple negative status, TN) in essential thrombocythemia (ET) indicates a biological heterogeneity of the disease and can determine its clinical forms. The aim was to evaluate the association of molecular genetic markers with the clinical form and the prognosis of ET. Materials & Methods. We analyzed the data of 240 patients with ET at the age of 20-91 years (median age 58.7 years), who were observed in the Russian Research Institute of Hematology and Transfusiology from 1999 to 2016 (median observation period 37.2 months). Results. The JAK2V617F (JAK2+) mutation was found in 182 (75.9 %) of 240 patients. CALR (CALR+) mutations were found in 30 (12.5 %): type 1 (CALP7+) mutations in 13/30 (43.3 %) and type 2 (CALR2+) in 17/30 (56.7 %). MPL (MPL+) mutations were found in only 2 (0.8 %) of 240 patients. None of the mutations were detected in 26 (10.8 %) of 240 patients (TN status). Significantly higher platelet counts were observed in CALP7+ and CALR2+ subgroups during the primary diagnosis of ET compared with JAK2+ and TN groups. The mean platelet counts were 1252 * 10⁹/L for CALR2+ and 1079 * 10⁹/L for CALP7+ vs 841 * 10⁹/L (p < 0.001; p = 0.06) and 775 * 10⁹/L (p < 0.001; p = 0.04) for JAK2+ and TN, respectively. Thrombosis was diagnosed in 50 (27.4 %) of 182 patients of the JAK2+ subgroup, in 8 (30.7 %) of the 26 patients of the TN subgroup, and in 2 (18.2 %) of 11 patients of the CALP7+ subgroup. No thrombosis was found in the CALR2+ and MPL+ subgroups (p < 0.001). In general, the CALP7+ status was characterized as the most favorable in terms of prognosis (5-year overall survival rate of 100 %), compared to the least favorable TN status (5-year overall survival rate of 85 %). Conclusion. Mutations in the CALR gene were characterized by a more favorable prognosis in comparison with JAK2+and TN, as well as a decrease in the risk and frequency of thrombosis, despite higher platelet counts. TN-status of ET was associated with unfavorable prognosis.

РЕФЕРАТАктуальность. Появившиеся в последние годы новые препараты -миметики тромбопоэтина -позволяют с высокой долей вероятности получить клинический от-вет у больных с хронической формой идиопатической тромбоцитопенической пурпуры (ИТП), резистентной к глюкокортикоидам. Вместе с тем высокая стоимость препаратов и необходимость длительного лечения тре-буют проведения фармакоэкономического анализа ка-сательно использования агонистов рецепторов тромбо-поэтина при лечении ИТП. Цель. Оценить эффективность затрат на терапию хро-нической формы ИТП, резистентной к глюкокортикои-дам, с помощью миметиков тромбопоэтина (ромиплости-ма и элтромбопага) и иммуносупрессивной терапии. Материалы и методы. Проводилось марковское модели-рование диагностики и лечения ИТП в соответствии с На-циональными рекомендациями по диагностике и лечению первичной ИТП. Анализ применения агонистов рецепто-ров тромбопоэтина (ромиплостима и элтромбопага) и им-муносупрессивной терапии осуществляли с позиции си-стемы здравоохранения методом «стоимость-полезность». Временной период (горизонт) исследования -5 лет. Результаты. Миметики тромбопоэтина характеризуются более высокой стоимостью, но также большей эффектив-ностью по сравнению с иммуносупрессивной терапией. Эффективность затрат для достижения 1 QALY при лече-нии элтромбопагом составляет 1,33 млн рублей, ромипло-стимом -4,2 млн рублей, а при иммуносупрессивной те-рапии -0,17 млн рублей. Наименьшие дополнительные затраты при сравнении с иммуносупрессивной терапией имела стратегия использования элтромбопага, тогда как для использования ромиплостима необходимо было почти в 2 раза больше средств. Установлены пороговые значения соотношения стоимостей агонистов рецепто-ров тромбопоэтина для экономического обоснования выбора препарата. Использование ромиплостима может быть экономически оправданным при стоимости 1 флако- PHARMACOECONOMICS ABSTRACTBackground. New medications, thrombopoietin mimetics which were recently introduced into clinical practice allowed to achieve clinical response in patients with chronic glucocorticoid-resistant idiopathic thrombocytopenic purpura (ITP). However, the high cost and the need for long-term administration necessitate a pharmacoeconomic analysis of the use of thrombopoietin receptors agonists in the treatment of ITP. Aim. To assess the cost-eff ectiveness of the use of thrombopoietin mimetics (romiplostim and eltrombopag) and immunosuppressive therapy in the treatment of chronic glucocorticoid-resistant ITP. Materials & Methods. The Markov modelling of diagnosis and treatment of ITP was conducted in accordance with the National guidelines for diagnosis and treatment of primary ITP. The cost-benefi t analysis of the use of thrombopoietin receptors agonists (romiplostim and eltrombopag) and immunosuppressive therapy was performed. The time period (horizon) of the study was 5 years. Results. The therapy with thrombopoietin mimetics had higher costs but was shown to be more eff ective compared to immunosuppressive therapy. The cost-eff ectiveness for achieving 1 QALY i...

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters. Materials & Methods. Cell samples of peripheral blood cyta-pheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry. Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation. Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.