Background . Paroxysmal nocturnal hemoglobinuria is a rare clonal disease of the hematopoietic system, with the key manifestations of hemolytic anemia, a high thrombosis rate, and bone marrow failure. Despite the high efficacy of C5‑inhibitors in intravascular hemolysis cessation, a significant proportion of patients remain anemic. Causes of a sub‑optimal response may include C3‑mediated extravascular (intracellular) hemolysis, residual intravascular hemolysis, or bone marrow failure. Aim . To analyze the results of pathogenetic therapy in patients with paroxysmal nocturnal hemoglobinuria. Materials and methods. The study included 55 patients with paroxysmal nocturnal hemoglobinuria receiving complement C5 inhibitors for at least 6 months. Results. Suboptimal hematological response was observed in 31/55 (56 %) patients. The most common cause of anemia in the partial response group was C3‑mediated extravascular hemolysis in 8/10 (80 %), while bone marrow failure predominated (57 %) in the minor response group. Conclusion . The study showed a high frequency of suboptimal response to pathogenetic therapy and necessity of ac‑curate determination of leading cause of persistent anemia in order to modify therapy or switch to other drugs.

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. The main causes of HUS are infections caused by Shiga toxin-producing bacteria: hemorrhagic Escherichia coli and Shigella dysenteriae type 1. They account for up to 90% of all cases of HUS. The remaining 10% represent a heterogeneous group of diseases collectively referred to as atypical HUS. The pathogenesis of most cases of atypical HUS is based on congenital or acquired disorders in the complement system. Over the past decades, evidence has accumulated that, in addition to E. coli and Sh. dysenteriae type 1, a wide variety of bacterial and viral infections, including the pathogens of pneumonia Streptococcus pneumoniae, immunodeficiency virus, H1N1 influenza, and a new coronavirus infection, can cause the development of HUS. In particular, infectious diseases act as the main cause of recurrence of atypical HUS. This review presents summarized data from recent studies, indicating that in various types of infectious HUS, disturbances in the complement system are a key pathogenetic factor. The links in the complement system are considered, the dysregulation of which in bacterial and viral infections can lead to complement hyperactivation with subsequent damage to the microvascular endothelium and the development of acute renal failure.

New guidelines on diagnosis and treatment of a primary immune thrombocytopenia (ITP) in children and adults, on the basis of modern pathogenesis conceptions and considering possibilities of hematological practice in Russia are presented. Guidelines are based on a consensus of international and Russian experts on ITP. Diagnostic features of ITP are noted and various I, II and III lines treatment, including new effective medical products which have recently appeared in Russia, in particular, trombopoietin receptor agonists (romiplostim, eltrombopag), considerably expanded conservative treatment possibilities are offered. The presented guidelines can help hematologists to develop individual schedule for each given patients with ITP and to improve patients quality of life.

Epstein-Barr virus (EBV) is ubiquitous, being identified in 90-95 % of adults. Its reactivation in immunodeficiency conditions often leads to clonal transformation of B-lymphocytes and development of B-cell lymphoproliferative diseases (LPD) and B-cell lymphomas. At the same time, in the countries of North-East and East Asia, as well as Latin America, non-immunocompromised patients sometimes demonstrate the development of EBV-associated T-cell lymphoproliferative diseases. The present paper reports a rare case of EBV-associated systemic T-LPD with lymphadenopathy, splenomegaly as well as acute autoimmune hemolytic anemia in a man of Caucasian race. Complex analysis of anamnestic, pathomorphological, and laboratory data allowed to distinguish this disease from T-cell lymphoma and choose the appropriate patient management strategy.

— Von Willebrand factor (vWF), the key component of hemostasis, is synthesized in endothelial cells and megakaryocytes and released into the blood as high molecular weight multimeric glycoproteins weighing up to 20 million Daltons. Blood plasma metalloprotease ADAMTS13 cleaves ultra-large vWF multimers to smaller multimeric and oligomeric molecules. The vWF molecules attach to the sites of damage at the surface of arterioles and capillaries and unfold under conditions of shear stress. On the unfolded vWF molecule, the regions interacting with receptors on the platelet membrane are exposed. After binding to the vWF filaments, platelets are activated; platelets circulating in the vessels are additionally attached to them, leading to thrombus formation, blocking of microvessels, and cessation of bleeding. This review describes the history of the discovery of vWF, presents data on the mechanisms of vWF secretion and its structure, and characterizes the processes of vWF metabolism in the body under normal and pathological conditions.

This article presents the results of studies on high prevalence of left ventricular noncompaction (LVNC) in patients with secondary hemochromatosis (SH). We also included case reports of patients with SH and LVNC and compared imaging data using modified modern criteria for LVNC and molecular genetic testing (MGT). In patients with cardiac hemochromatosis, left ventricular noncompaction is noted, the nature of which is most likely secondary. In order to confirm this hypothesis, a prospective observational study, including family screening and MGT, is required.

We present a ten-year follow-up of a patient with severe congenital thrombotic thrombocytopenic purpura (TTP), who received permanent replacement therapy with freshly frozen plasma (FFP) transfusions. At presentation, the patient had no activity of plasma ADAMTS-13 and an increased concentration of von Willebrand factor multimers. During treatment, the disease was complicated by occasional acute renal failure and hepatic dysfunction. These complications developed when the intervals between plasmapheresis were extended, and were partially reversible. Given the absense of ADAMTS-13 inhibitor and the early childhood history of the signs of the disease (petechiae during infections), the patient was diagnosed with congenital TTP. After the nature of the disease was thus established, plasmapheresis was replaced with regular transfusions of FFP. The intervals between transfusions were determined by monitoring the falling platelet counts and ADAMTS-13 activity. As a result of the treatment over the past 6 years, there have been no serious complications, and the patient leads an active lifestyle, studies and works. Over the course of the treatment, the patient received over 150 transfusions of FFP (amounting to over 100 liters of FFP), but despite the numerous transfusions, the patient has not contracted viral hepatitis or HIV. Thus, a tailored replacement therapy with FFP administered to a patient with congenital TTP helped to avoid severe debilitating complications, while the use of quarantine or virus-inactivated FFP minimized the risk of transfusion related infections.

Adherence to proper indications for red blood cells (RBC) transfusion is essential because of its potential adverse effects and costs of therapy. Aim of these recommendations is to summarize typed of RBC concentrates and indications for RBC transfusions among different categories of the patients. Methods. The methodological approaches are based on the recommendations of the Russian expert council (leading specialists of the Russian Federation) and literature search for randomized clinical trials evaluating RBC storage duration, hemoglobin thresholds and clinical indications for RBC transfusion without language restrictions. Results. The draft clinical guidelines were reviewed on February 1, 2018 at First Russian Transfusiology Congress of the (Vladivostok). The main types of RBC concentrates, storage duration, transport conditions and indications for RBC transfusions are presented. The indications for RBC transfusions are analyzed for various clinical conditions (in obstetrics, neonatology, hematology, cardiology, neurosurgery, nephrology, in patients with sepsis and septic shock, patients with acute blood loss, in patients after hematopoietic stem cell and organ transplantation). Conclusion. The recommendations are intended for doctors of various specialties, health administrators, medical students.

The paper describes a case of autoimmune hemolytic anemia (AIHA) in a 27-year-old woman whose examination revealed mesenteric teratoma. AIHA was characterized by a hypertensive crisis and a temporary response to corticosteroid therapy that was complicated by the development of somatogenic psychosis and discontinued. A relapse of hemolysis developed 6 months later. The patient underwent laparoscopic splenectomy and removal of mesenteric root teratoma. Immediately after surgery, a hematological response was obtained as relief of hemolysis and restoration of a normal hemoglobin level. There is a sustained remission of AIHA for the next 16 months.

Autoimmune hemolytic anemia (AIHA) is a rare blood disease associated with the production of auto-antibodies and autoimmune hemolysis. A critical role of B-cells in the development of AIHA has been demonstrated before. Here, we present the analysis of the clonal T-cell populations in patients with AIHA. Thirty-three patients with AIHA were included in this study. Thirteen patients with other anemias, 14 patients with other autoimmune conditions (SLE - 6, RA - 8) and 20 healthy donors were included in the study as a control group. The clonality of T-cell was evaluated by the assessment of the T-cell receptor gamma and beta chain gene rearrangements (TCRG and TCRB). The incidence of T-cell monoclonality detected in patients with AIHA was significantly higher compared to the control group. The persistence of T-cell clones did not correlate with the level of hemoglobin and other signs of remission or relapse and did not disappear after the therapy and clinical improvement (observation period was between 1 and 10 years). There was no correlation between the T-cell clonality and the gender, age, splenectomy, duration or severity of the disease. Fractionation of T-lymphocytes (CD4+, CD8+, CD4+25+) revealed that the monoclonal T-cells belonged to the CD8+ sub-population. We assume that besides a possible causative role of the T-cell clones in AIHA to autoimmune process, these clones do not directly participate in the development and maintenance of hemolysis. Most of the AIHA patients (48.5%) demonstrated a T-cell monoclonality, which requires monitoring and should be distinguished from T-cell tumors.

По инициативе Российского национального гематологического общества, исследовательской группой по изучению идиопатической тромбоцитопенической пурпуры (первичной иммунной тромбоцитопении) ИТП разработаны клинические рекомендации по ее диагностике и лечению. Целью рекомендаций является стандартизация диагностических и лечебных подходов при ИТП в России. Используемые методологические подходы основаны на принципах доказательной медицины, в их основе лежат рекомендации Российского совета экспертов по диагностике и лечению больных первичной иммунной тромбоцитопенией и российский опыт ведения больных ИТП, а также руководство Международной рабочей группы по изучению первичной иммунной тромбоцитопении (International Working Group), решения Международного консенсуса по диагностике и лечению ИТП и рекомендации европейских и американских обществ гематологов по изучению данного заболевания. Национальные клинические рекомендации разработаны многоцентровой исследовательской группой по изучению ИТП в России. В их разработке принимали участие ведущие специалисты 8 гематологических центров РФ.

The research group for studies of idiopathic thrombocytopenic purpura (ITP) has developed clinical recommendations for the diagnosis and treatment of this disease. The aim of the recommendations is standardization of the diagnostic and therapeutic approaches in Russia. The current methodological approaches proceed from the conclusive medicine philosophy and are based on the recommendations of the Russian Expert Council for the diagnosis and therapy of patients with primary immune thrombocytopenia and the experience gained in the treatment of ITP patients (primary immune thrombocytopenia) in Russia, as well as on recommendations of the International Working Group for studies of primary immune thrombocytopenia, decisions of the International Consensus on ITP diagnosis and therapy, and recommendations of the European and American Societies of Hematologists for ITP studies. The recommendations are developed by the multicenter research group for ITP studies. Working groups from 8 leading institutions of Russia contributed to the development of clinical recommendations.

Primary immune thrombocytopenia (ITP) is a rare (orphan) blood disease. Most frequent manifestations of ITP are purpura, petechiae and bleedings with many patients have either no symptoms or minimal bleedings manifestation. The management of ITP varies widely and must be based on current international recommendations and individual assessment of clinical course. The paper presents the results of interim analysis of clinical course and therapeutic approaches in the Russian register of ITP patients with immune thrombocytopenia and literature review about ITP treatment approaches.

Primary immune thrombocytopenia (ITP) is a rare (orphan) blood disease. Most frequent manifestations of ITP are purpura, petechiae and bleedings with many patients have either no symptoms or minimal bleedings manifestation. The management of ITP varies widely and must be based on current international recommendations and individual assessment of clinical course. The paper presents the results of interim analysis of clinical course and therapeutic approaches in the Russian register of ITP patients with immune thrombocytopenia and literature review about ITP treatment approaches.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a hypercoagulable state associated with acute hemolysis. Eculizumab is used to reduce the intensity of intravascular hemolysis in PNH patients.The hemostatic status of three patients with PNH was assessed during eculizumab treatment by D-dimer assay and the global assays: thromboelastography (TEG), thrombin generation test (TGT), and thrombodynamics (TD). In the state of hemolytic crisis before the therapy D-dimer concentration was increased in two patients accompanied by hypercoagulation changes in TEG parameter angle (alpha). TD parameter the clot growth velocity (V) revealed hypercoagulability while TGT parameter ETP was within the normal range in all patients.The lactate dehydrogenase (LDH) activity decreased during the 8 months of eculizumab therapy. The physical health was improved, the frequency of hemolytic crisis decreased. Patients periodically exhibited hypercoagulable state: the mean values alpha = 38 +/- 11 degrees (with normal range 20-40 degrees), ETP = 1311 +/- 442 nM.min (with normal range 800-1560 nM.min), V = 31 +/- 4 mu m/min (with normal range 20-29 mu m/min). During the eculizumab therapy two patients had the repeated clinical manifestation of acute hemolytic crisis, the parameters of the global tests were increased compared to the previous measurement.The global hemostasis tests TEG, TGT and TD revealed hypercoagulability in patients with PNH during eculizumab therapy. (C) 2014 Elsevier Inc. All rights reserved.