Background. Gaucher disease (GD) is a rare hereditary condition, which represents the most common form of lysosomal storage diseases. Enzyme replacement therapy (ERT) with recombinant glucocerebrosidase is used for the treatment of type 1 and type 3 GD. Imiglucerase (recombinant glucocerebrosidase) is the first biotechnological ERT medication possessing confirmed clinical efficacy and safety.

Aim. To compare the efficacy and safety of the biosimilar drug Glurazyme and the reference drug Cerezyme during ERT therapy in patients with type 1 GD.

Materials and methods. Thirty patients aged from 19 to 63 years (33 ± 9.7 years) with a stable course of type 1 GD were enrolled in the study. The patients were randomly divided into two equal treatment groups, one of which received Glurazyme and the other received the reference drug Cerezyme. In both groups, the drugs were used in doses of 15–40 U/kg intravenously once every 14 days for 52 weeks.

Results. At the end of the study, at week 52 (primary endpoint of efficacy), both groups demonstrated a similar increase in hemoglobin concentration compared to the baseline data. In both groups, the average increase in hemoglobin concentration was 4.8 g/l, with this parameter varying between the groups by 0.1 g/l. At week 52, the calculated 95% confidence interval for the difference in hemoglobin concentration did not cross the non-inferiority margin of 18 g/l, which had been specified as the lower level of drug efficacy. This led to the conclusion that the studied drug Glurazyme is not inferior to Cerezyme in terms of efficacy. A comparison of the treatment groups by secondary endpoints of efficacy revealed: no decrease in hemoglobin concentration by more than 20 % in both groups; no differences between the groups by the number of patients with a change in platelet concentration relative to the baseline values; no increase in the spleen and liver volume by more than 20 and 10 %, respectively, in both groups. The doses of the drug under study and the reference drug remained unchanged during the research. The concentration of chemokine CCL-18 decreased slightly in 10 patients (64.3 %) and 6 patients (40 %) in the Glurazyme group and the Cerezyme group, respectively. The proportion of patients with improved physical and mental health components was 57.1 and 57.1 %, respectively, in the Glurazyme group compared to 73.3 and 60 %, respectively, in the Cerezyme group. Changes in the state of the bone tissue and the reserves of accumulated metabolites in the bone marrow showed a similar decrease in the severity of bone marrow infiltration in both groups.

Conclusions. Glurazyme and Cerezyme showed comparable parameters of efficacy and safety in patients with GD type 1 during long-term enzyme replacement therapy.

Background. The timely reconstitution of the donor-derived immune system is a key factor in the prevention of such post-transplant complications as graft versus host disease, relapse or secondary tumours and various infections. These complications affect the long-term survival of patients after allogeneic stem cell transplantation.

Aim — to describe the main stages of T Cell–mediated immune recovery in patients after allogeneic stem cell transplantation.

General findings. T-cell–mediated immunity is responsible for anti-infective and anti-tumour immune response. The early post-transplant period is characterized by the thymus-independent pathway of T-cell recovery largely involving proliferation of mature donor T cells, which were transplanted to the patient together with hematopoietic stem cells. To a lesser extent, this recovery pathway is realized through the expansion of host naïve and memory T cells, which survived after conditioning. Thymus-dependent reconstitution involves generation of de novo naïve T cells and subsequent formation of a pool of memory T-cells providing the main immunological effects — graft versus tumour and graft versus host reactions. A better understanding of the T-cell immune reconstitution process is important for selecting optimized pre-transplant conditioning regimens and patient-specific immunosuppressive therapy approaches, thus reducing the risks of post-transplant complications and improving the long-term survival of patients after allogeneic stem cell transplantation.

Background. Nijmegen breakage syndrome is a rare hereditary autosomal recessive disorder characterized by microcephaly, combined primary immunodeficiency, sensitivity to radioactive radiation and liability to tumours of various nature (in particular, those developing in the lymphatic tissue). This syndrome is part of a group of diseases characterized by chromosomal instability. This disease develops as a result of mutations in the NBS1 gene, which is responsible for repairing DNA double-stranded breaks.

Aim. To describe a clinical case of the diagnosis and treatment of T-cell acute lymphoblastic leukemia in a patient with Nijmegen syndrome, which was first diagnosed in adulthood.

General findings. A clinical case of the diagnosis and treatment of Nijmegen syndrome in a young man with de novo T-cell acute lymphoblastic leukemia is presented. The difficulty of early diagnosis of hereditary genetic syndromes is demonstrated. The genetic character of such conditions is revealed over time, when children and young adults begin to develop long-term complications, in particular tumours of various origins. Early detection of hereditary genetic syndromes in children is of great importance.

Background. This study is devoted to a rare variation of the -D- phenotype . The -D- phenotype was first discovered by R. Race, R. Sanger and J.G. Selwyn in 1951. In Russia, the phenotype -D- was first discovered by V. Morokov in 1985. Typically, the -D- phenotype is detected when physicians examine post-transfusion complications or hemolytic disease of the newborn, since such patients demonstrate high antibody titres to absent antigens. In the present study, the -D- phenotype was detected in a primary blood donor at the clinical laboratory of the Ulyanovsk Regional Blood Transfusion Station (Ulyanovsk, Russia). Aim. To study specific features of immunohematological and hematological blood parameters in a donor with a rare variation of the -D- phenotype.

Materials and methods. The detection of the -D- phenotype by immunohematological methods was carried out using automatic analysers. Molecular DNA typing was used to confirm the -D- phenotype. The shape of erythrocytes of the donor with the -D- phenotype was evaluated using an atomic force microscope. The characteristics of the erythroid lineage were studied using an automatic hematological analyser.

Results. The -D- phenotype was detected in a primary blood donor. Due to the extreme rarity of the -D- phenotype and the lack of programmed algorithms, the validation of the results by automatic analysers was incorrect. Of critical importance was the visual assessment of gel ID cards by the medical staff. Genotyping confirmed the lack of C, c, E, e, C^w specificities in the RHCE gene. The hematological parameters of the donor were within the age norm. An assessment of the image of a cytological blood preparation did not reveal changes in the shape of erythrocytes and their size.

Conclusions. The primary determination of the -D- phenotype using automatic immunohematological analysers can be complicated by the impossibility of validating the results, the incorrect operation of the installed software and the need for expert evaluation of blood samples by the staff. The presented case of the -D- phenotype was not associated with changes in the shape of erythrocytes and blood hematological parameters.

Background. Protein C deficiency is a rare condition. However, this pathology occurs more frequently in premature babies with cyanotic heart disease.

Aim. To present a clinical case of an intraoperative detection of protein C deficiency in a patient operated for cyanotic heart disease.

General findings. A clinical case of an intraoperative recurrent thrombosis of systemic-to-pulmonary shunts in a newborn patient with cyanotic heart disease is described. Newborn and premature babies with cyanotic heart defects belong to a high risk group of developing intraoperative thrombosis due to a deficiency of natural anticoagulants, which can occur as a result of genetically conditioned protein C deficiency, prematurity, immaturity of the liver or its reduced synthetic function, heart failure and hypoxemia. Additional pre-operative screening is required for detecting a deficiency of natural anticoagulants in this group of patients. The hospitals that perform such surgery should be equipped with protein C concentrates.

Background. Massive blood loss is one of the main causes of deaths and complications both in patients requiring extensive surgical interventions and those with severe trauma.

Aim. To analyse available publications devoted to the definition, pathogenesis, diagnosis and intensive care of acute massive blood loss in children.

Materials and methods. The conducted analysis involved 102 publications by Russian and foreign authors from the PubMed database devoted to the problem of massive blood loss in children.

General findings. The paper presents modern definitions of massive blood loss in children. Special attention is paid to the pathogenesis, diagnosis and treatment of massive blood loss in severe trauma cases. The principles of correcting the deficiency of circulating blood volume, the use of inotropic and vasopressor drugs, as well as the elimination of severe anemia and hemostasis disorders, are considered. Publications devoted to the search for an optimal ratio of globular and plasma volumes during the transfusion of blood components are reviewed. It is shown that the reviewed publications report conflicting opinions regarding the use of antifibrinolytic medications. At the same time, the high efficiency of tranexamic acid and its positive effect on the functional outcome in patients with severe trauma is demonstrated. In order to optimize approaches to the management of massive blood loss in children, additional multicenter studies are required. These studies should consider the effect of the underlying disease that caused massive blood loss, as well as the treatment and diagnostic capacity of hospitals.

Background. Cryoprecipitate is made from fresh-frozen plasma (FFP) and contains fibrinogen, factor VIII, factor XIII, von Willebrand factor, fibronectin and fibrinogen.

Aim. To provide information on the composition and methods of production, storage, transportation and clinical use of cryoprecipitate.

General findings. Cyoprecipitate is manufactured by slowly thawing FFP at 1–6°C. This precipitates out cryoproteins: factor VIII, von Willebrand factor, factor XIII, fibronectin and fibrinogen. After centrifugation, the cryoproteins are resuspended in a reduced volume of plasma. Cryoprecipitate is stored at temperatures not exceeding –25° С for 36 months. Indications for cryoprecipitate transfusion are hemophilia A, von Willebrand disease, factor XIII deficiency, congenital afibrinogenemia and hypofibrinogenemia, acquired hypofibrinogenemia. These indications can occur in obstetrics, neonatology, cardiac surgery, neurosurgery, hematology, orthopaedics, and general surgery during liver transplantation and disseminated intravascular coagulation.