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The article defines reference values for activated partial thromboplastin time, Quick’s value, INR, thrombin time, fibrinogen, antithrombin and II, V, VII, VIII, IX, X, XI and XII coagulation factors, according to existing standards on the automated Sysmex CS‑2000i analyzer.The aim of the study. To determine reference values for routine and specific parameters of the hemostasis, which may vary depending on the type of analyzer and utilized reagents.Materials and methods. After receiving informed consent from donors for medical survey and blood donation, blood samples were obtained from 100 healthy donors: 64 (64%) males и 36 (36%) females. We established reference values with the Sysmex CS‑2000i (Sysmex, Japan) hemostasis analyzer and reagents from Siemens (Siemens Healthcare, Germany).Results. The data obtained were compared with the literature data and the data presented in the instructions for the reagents used. The results obtained for activated partial thromboplastin time (23.59–35.69 sec), fibrinogen (1.67–3.59 g/l) and antithrombin (67.65–114.89%) are comparable to the available data. There are no data on other studied parameters of hemostasis for the Sysmex CS‑2000i analyzer and the reagents used in the work. The obtained reference intervals are consistent with the recommendations of the manufacturer.Conclusions. Reference values vary significantly depending on the analytical systems and reagent kits used, which confirms the need for local derivation or validation of reference intervals for each specific analytical system and in each laboratory.

Introduction. Acquired hemophilia is a rare autoimmune disease caused by an inhibitor to clotting factor VIII (FVIII). It complicates the course of many diseases, in particular autoimmune diseases, and in women is often associated with pregnancy.Aim — to present a case of successful treatment of a patient with acquired hemophilia using long-term continuous infusion of rFVIIa and inhibitor eradication as a result of immunosuppressive therapy.Main findings. A clinical observation of severe hemorrhagic syndrome in a patient with acquired hemophilia associated with pregnancy is presented. Uterine bleeding in the patient after spontaneous delivery, refractory to standard hemorrhagic syndrome treatment, required multiple surgical interventions. Laboratory tests showed prolongation of APTT, CT in the INTEM rotational thromboelastometry test, a decrease in plasma FVIII activity and presence of inhibitor to FVIII. Vacuum-assisted closure was applied to treat infected laparotomy wound. Therapy for acquired hemophilia consisted of hemostatic therapy and the inhibitor eradication. Hemostatic therapy included a continuous infusion of rFVIIa at a rate of 30 μg/kg/h with a gradual decrease up to 9.6 μg/kg/h, as well as its fractional administration before every surgery at a dosage of 80 μg/kg. The effectiveness of the therapy was assessed by the dynamics of CT in the INTEM test and the shortening of the APTT. The inhibitor eradication was achieved by prednisolone therapy, combined immunosuppression with rituximab and azathioprine, followed by its replacement with cyclophosphamide. As a result, the hemorrhage was stopped, reference plasma activity of FVIII and eradication of the inhibitor were reached.

Introduction. In most cases, in patients with hereditary fibrinogen deficiency, clinical manifestations are represented by bleeding of varying intensity and localization. However, the clinical picture of hereditary fibrinogen deficiency can also be represented by thrombosis.Aim — to characterize the detected mutations in fibrinogen genes and to analyze prothrombotic factors in patients with hereditary hypofibrinogenemia and thrombosis.Materials and methods. Forty-nine patients with hereditary hypofibrinogenemia were observed, of which 46 patients had no history of thrombosis and 3 patients had a confirmed history of thrombosis. These 3 patients made up the study group.Results. Heterozygous mutations were found in all 3 patients in the fibrinogen gamma chain gene (FGG), one of them had a previously undescribed deletion g.2653_2684+211del, p.(Asp167Glufs*2), which removes 32 terminal nucleotides of the fifth exon of the FGG gene and leads to the formation of a stop codon in place of amino acid 168. In two other patients, there were missense mutations c.1140T>A, p.(Cys365Ser) and c.1114A>T, p.(Asp356Val), which can determine the thrombogenic properties of the altered protein structure of fibrinogen. Other prothrombotic factors were also identified: genetic polymorphisms of low thrombotic risk, surgery, taking combined oral contraceptives.Conclusion. Hereditary fibrinogen deficiency does not play a protective role in relation to the development of thrombosis and may cause the development of thrombosis, which is associated with its multifunctional role in the hemostasis system. The pathogenesis of thrombosis in patients with hereditary hypofibrinogenemia is multifactorial and may be associated with the characteristics of the main protein defect and the coexistence of hereditary and acquired thrombotic risk factors (surgical interventions, taking combined oral contraceptives, etc.).

Performance of surgical interventions in patients with severe hemophilia A on emicizumab requires the development of a protocol for the perioperative period management. Objective. To present the first experience of laparoscopic hernioplasty, hemostatic therapy and laboratory monitoring in a patient with severe hemophilia A on emicizumab. A transperitoneal hernioplasty was performed in a 31-year-old patient with severe hemophilia A on emicizumab. The patient received hemostatic therapy with recombinant FVIII for 5 days. Laboratory parameters (detection of FVIII via chromogenic and clotting methods, thromboelastography, determination of aPTT and FVII inhibitor titer) were monitored for 8 days. For a complete postoperative hemostasis, a significantly smaller amount of FVIII concentrate was required due to the lower frequency of administrations compared to similar surgical interventions in patients with severe hemophilia A who did not receive prophylactic therapy with emicizumab. According to thromboelastrography data, not a single episode of hypercoagulation was recorded. Emicizumab monotherapy can maintain adequate hemostasis during surgical procedures associated with a potentially low risk of perioperative bleeding in patients with hemophilia A. In other situations, the use of standard doses of FVIII concentrate concomitantly with emicizumab makes it possible to control hemostasis during postoperative period without the risk of thrombotic complications. The patient has signed a consent to the use of information, including photos, for research purposes and in publications.

Primary myelofibrosis is a myeloproliferative neoplasm that occurs de novo, characterized by clonal proliferation of stem cells, abnormal expression of cytokines, bone marrow fibrosis, hepatosplenomegaly as a result of extramedullary hematopoiesis, symptoms of tumor intoxication, cachexemia, peripheral blood leukoerythroblastosis, leukemic progression and low survival. Primary myelofibrosis is a chronic incurable disease. The aims of therapy: preventing progression, increasing overall survival, improving quality of life. The choice of therapeutic tactics is limited. Allogenic hematopoietic stem cell transplantation is the only method that gives a chance for a cure. The role of mutations in a number of genes in the early identification of candidates for allogeneic hematopoietic stem cell transplantation is being actively studied. The article describes the clinical case of the detection ofASXL1gene mutations in a patient with prefibrous primary myelofibrosis. The diagnosis was established on the basis of WHO criteria 2016. The examination revealed a mutation ofASXL1. Interferon alfa therapy is carried out, against the background of which clinico-hematological remission has been achieved. Despite the identified mutation, the patient is not a candidate for allogeneic hematopoietic stem cell transplantation. Given the unfavorable prognostic value of theASXL1mutation, the patient is subject to active dynamic observation and aggressive therapeutic tactics when signs of disease progression appear.Первичный миелофиброз (ПМФ) представляет собой миелопролиферативное новообразование, которое возникает de novo, характеризуется клональной пролиферацией стволовых клеток, аномальной экспрессией цитокинов, фиброзом костного мозга, гепатоспленомегалией как следствие экстрамедуллярного гемопоэза, симптомами опухолевой интоксикации, кахексией, лейкоэритробластозом в периферической крови, лейкемической прогрессией и невысокой выживаемостью. ПМФ является хроническим неизлечимым заболеванием. Цели терапии: предупреждение прогрессии, увеличение общей выживаемости, улучшение качества жизни. Выбор лечебной тактики ограничен. Трансплантация аллогенных гемопоэтических стволовых клеток (алло-ТГСК) единственный метод, дающий шанс на излечение. В настоящее время активно изучается роль мутаций ряда генов в раннем выявлении кандидатов для алло-ТГСК. В статье представлено описание клинического случая выявления мутации гена ASXL1 у больного префиброзным ПМФ. Диагноз установлен на основании критериев Всемирной организации здравоохранения 2016 г. При обследовании выявлена мутация ASXL1. Проводится терапия интерфероном альфа, в результате которой достигнута клинико-гематологическая ремиссия. Несмотря на выявленную мутацию, пациент не является кандидатом для алло-ТГСК. Учитывая неблагоприятное прогностическое значение мутации ASXL1, пациент подлежит активному динамическому наблюдению и агрессивной терапевтической тактике при появлении признаков прогрессирования заболевания.

Introduction.The term “cryoglobulinemia” is currently used to identify immunoglobulins in vitro in the blood serum that precipitate at temperatures below 37 °C; in vivo they form immune complexes that can be deposited in small vessels and activate the complement system with the development of leukocytoclastic vasculitis. Cryoglobulinemia may develop in various lymphoproliferative, autoimmune and infectious diseases.Aim of study.To develop the technique of plasma proteins cryofraction (selective plasmapheresis with the use of heparin as a stimulant of fibronectin opsonic activity and purified autoplasma to compensate for the removed volume), to evaluate the effectiveness and tolerability of the developed technique in the treatment of patients with cryoglobulinemia.Materials and methods.159 patients were treated (120 women and 39 men aged 21 to 83 years).Research results.Heparinocryofraction technique is a highly effective method of extracorporeal blood purification, which allows to selectively remove from the patients’ plasma such pathological components as cryoglobulins (up to 100% of the initial content), adhesive proteins (up to 84% of the initial content), fibronectin and immune complexes (up to 7% of the initial content). It is possible to reduce significantly and reliably the level of cryoglobulins, circulating immune complexes, non-specific markers of inflammation, daily proteinuria, as well as to normalize the initially reduced concentration of complement components and hemoglobin in the blood of patients with cryoglobulinemia before and after the procedure of cryofractionation. Purified by the proposed method autoplasma is a solution of albumin and normal immunoglobulins, which allows to use it for plasma substitution during a course of cryofractionation procedures, on average 7 procedures with an interval of 1–2 days.Conclusion.The technique of cryofractionation using heparin and purified autoplasma can and should be widely used in the complex treatment of patients with cryoglobulinemia. Carrying out 6–-7 sessions of plasma cryofractionation allows to remove cryoglobulins from plasma effectively and selectively. Application of purified autoplasma allows to avoid using of blood preparations in plasmapheresis. The proposed method allows to significantly improve the efficiency and tolerance of medication therapy and increase the duration of disease remission.

Thrombosis is a serious and extremely dangerous disease that has a negative impact on the quality and longevity. Antiphospholipid syndrome (APS) is a pathology characterized by recurring venous, arterial, microvasculature thrombosis, pregnancy pathology with loss of the fetus and the synthesis of antiphospholipid antibodies. A high risk of thrombotic complications is also observed in patients with myeloproliferative neoplasms (MPN). This article presents a description of three clinical cases of Ph - negative myeloproliferative diseases, occurring in conjunction with APS. In all cases, recurrent thrombosis allowed to suspect the presence of two diseases - MPN and APS.Тромбоз является тяжелым и крайне опасным заболеванием, которое оказывает негативное влияние на качество и продолжительность жизни. Антифосфолипидный синдром (АФС) характеризуется повторяющимися тромбозами венозного, артериального, микроциркуляторного русла, патологией беременности с потерей плода и синтезом антифосфолипидных антител. Высокий риск тромботических осложнений также наблюдается у больных миелопролиферативными заболеваниями (МПЗ). Представлено описание трех клинических случаев Ph-негативных МПЗ, протекающих совместно с АФС. Во всех случаях рецидивирующие тромбозы позволили заподозрить наличие двух заболеваний - МПЗ и АФС.