Background. Polymorphisms in the UGT1А1 gene (especially the homozygous (TA)7/(TA)7genotype), which encodes the uridine diphosphate glucuronyltransferase 1 (UDP-GT) enzyme in hepatocytes, may manifest with isolated indirect hyperbilirubinemia. Hyperbilirubinemia is also most common laboratory abnormality in chronic myeloid leukemia (CML) patients treated by nilotinib.
Aim. To estimate the correlation between of UGT1А1 gene polymorphism and frequency of hyperbilirubinemia in CML patients treated by nilotinib.
Materials and methods. Our study included 100 CML patients treated by nilotinib. We analyzed their blood biochemistry, namely the level of bilirubin, the activity of liver enzymes (AST and ALT), the time to development of hyperbilirubinemia, and the time until normalization of blood biochemistry. We also studied the promoter region of the UGT1А1 gene in these patients with allele-specific polymerase chain reaction (AS-PCR).
Results. Indirect hyperbilirubinemia was observed in 84 (84%) of 100 patients. Of those, 41 (49%) had grade 1 hyperbilirubinemia, 33 (39%) had grade 2 hyperbilirubinemia, and 10 (12%) had grade 3 hyperbilirubinemia. Normal genotype (ТА)6/(ТА)6 was found in 71 (71%) patients, 19 (19%) patients had a heterozygous (ТА)6/(ТА)7 genotype, and 10 (10%) patients had a homozygous (ТА)7/(ТА)7 genotype. Eight of the 84 CML patients with hyperbilirubinemia (9,5%) had a transient elevation of ALT and AST: grade 1 in 1 case, grade 2 in 5 cases, and grade 3–4 in 2 cases.
Conclusion. In CML patients treated with nilotinib, grade 3 hyperbilirubinemia may be a sign of (ТА)7/(ТА)7 polymorphism in promoter region of the UGT1А1 gene. Low-grade hyperbilirubinemia occurs both in patients with normal UGT1А1 genotype and in patients heterozygous for the (ТА)7 polymorphism. No connection between UGT1А1 polymorphisms and elevated liver enzymes (ALT, AST) was established.

The aim of the study was to investigate the role of IKZF1 deletions in adult patients with Ph-negative (Ph–) and Ph-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL) who participated in the Russian Acute Lymphoblastic Leukemia (RALL) multicenter study. Our study included 67 patients with newly diagnosed B-cell ALL (49 Ph– and 18 Ph+ cases). Patients with Ph– B-cell ALL were treated according to RALL-2009 and RALL-2016 protocols and were followed up for a median of 18.1 months (range 1.5–93.4 months). Patients with Ph+ B-cell ALL were treated according to RALL- 2009 and RALL-2012 protocols with addition of tyrosine kinase inhibitors and were followed up for a median of 21.2 months (range 3.53–91.77 months). Intragenic deletions of IKZF1 were detected using breakpoint-specific fluorescent multiplex polymerase chain reaction. They were more frequently found in patients with Ph+ ALL (n = 10, 56%) than in patients with Ph– ALL (n = 9, 18%; p = 0.0074). No statistically significant association between IKZF1 deletions and age, sex, initial WCC of over 30 × 109/L, LDH above 750 U/mL, splenomegaly or neuroleukemia was observed. Notably, an expression of both myeloid antigens (MyAg) CD13 and СD33 was detected in almost half (n = 4,44%) of the Ph– ALL patients with IKZF1 deletions compared to only 1 patient (2.5%) without IKZF1 deletions (p = 0.0027). The presence of IKZF1 mutations was associated with persistence of minimal residual disease at 2 and 4 months of treatment, with higher leukemic cell counts; however, there seemed to be no observable differences in the long-term results of therapy regardless of whether or not IKZF1 mutations were present. Thus IKZF1 mutations in our study did not seem to be prognostically valuable for either Ph+ B-cell ALL or Ph– B-cell ALL, although they were shown to be associated with a delayed tumor clearance in patients with Ph– B-cell ALL.

Introduction. Chronic myeloid leukemia (CML) ranks third among hematological malignancies in Vietnam. Imatinib has become the standard therapy for CML patients in Vietnam since 2009.

Materials and methods. A phase IV clinical study for 1st line imatinib treatment of CML patients, carried out in 121 CML patients treated in NIHBT and receiving imatinib 400 mg/daily from 2010 to 2014.

Results. Cumulative CCyR and CMR were achieved in 82 (67.8%) and 80 (66.1%) of patients, respectively. There was a correlation between the time interval (from CML diagnosis to initiating imatinib treatment) and both complete cytogenetic (OR 0.158; p = 0.001) and molecular (OR 0.263; p = 0.018) responses. The analysis demonstrated that imatinib treatment minimized the prognostic impact of previously established prognostic factors in CML. The 3-year PFS and OS rates were 114 (94.6%) and 118 (97.5%), respectively. Hematologic adverse effects were mild with 1st and 2nd grades anemia, granulocytopenia and thrombocytopenia found in 17 (14%), 27 (22.3%) and 29 (23.9%) patients, respectively. The most commonly non-hematologic adverse effects occurred in 1st year of follow-up including periorbital edema, nausea, musculoskeletal pain, and rash.

Abstract. Daratumumab, the first therapeutic monoclonal antibody that binds to CD38, is used for treatment of patients with multiple myeloma. The CD38 transmembrane protein is highly expressed on the surface of malignant myeloma cells, but also, to a lesser extent, is expressed by many other types of cells, including red blood cells (RBCs). When daratumumab binds to CD38 expressed on RBCs, this may result in positive indirect antiglobulin tests (IAT) performed to identify immunological compatibility before RBC transfusions. Anti-CD38-specific agglutination may also variably affect autocontrol, direct antiglobulin test (DAT), and eluate tests.
The aim of the study was to develop a protocol for preventing CD38-specific agglutination in antiglobulin tests by treatment of RBCs with dithiothreitol (DTT).
Materials and methods. Between July 2016 and April 2017, 9 multiple myeloma patients undergoing daratumumab treatment were tested using routine methods in the Immunohematology Laboratory of the National Hematological Research Center in Moscow. The tests included ABO and Rh typing, extended phenotype matching, DAT, and IAT in LISS/Coombs gel cards. Tests were performed before and after treatment of RBCs with DTT.
Results. No daratumumab interference was observed in ABO, Rh, Kell, MNS or Fy typing with IgM antibodies. DAT and auto control were also negative in all patients. On the other hand, all patients showed daratumumabmediated positive IAT, which was resolved by treatment of RBCs with DTT.
Conclusions. Anti-CD38 antibodies interfere with serological tests. This interference can be resolved by treating RBCs with DTT. Blood banks and immunohematological laboratories should be informed that a patient is receiving treatment with anti-CD38.

Aim of the study. To compare the effects of tranexamic acid (TXA), factor XIII concentrate (FXIII) and fibrinogen concentrate on clot formation and fibrinolytic resistance in the in vitro model of hyperfibrinolysis induced by tissue- (tPA) vs urokinase-type (uPA) plasminogen activators.
Materials and methods. Citrated whole blood from 28 adult healthy volunteers was supplemented with 10 μg/ mL TXA, 2 IU/mL FXIII, or 3 mg/mL fibrinogen concentrate. Hyperfibrinolysis was induced by spiking the blood with tPA or uPA at their half-maximal effective concentrations (90 and 33 IU/mL, respectively). Clotting was induced by recalcification and addition of tissue factor and monitored using rotation thromboelastometry.
Results. The use of TXA increased maximal clot firmness in the presence of tPA and markedly inhibited clot lysis in the presence of any of the plasminogen activators. Supplementation of blood with FXIII significantly increased clot firmness and improved fibrinolytic resistance in the presence of either tPA or uPA. Supplementation with fibrinogen concentrate elicited a strikingly different effect on clot formation and lysis depending on the type of plasminogen activator. In the presence of tPA, fibrinogen concentrate significantly increased clot firmness and attenuated clot lysis. In contrast, in the presence of uPA, the use of fibrinogen markedly reduced clot firmness and promoted clot lysis. Similar effects of fibrinogen concentrate were observed in platelet-rich and microparticles-free plasma.
Conclusion. In hyperfibrinolysis, effect of the hemostatic drugs significantly depends on the type of plasminogen activator used. Therefore, mechanisms of hyperfibrinolysis should be taken into consideration while administering hemostatic drugs.

We present the results of testing 1231 venous blood samples from 1150 blood donors for V617F somatic mutation in the JAK2 gene. The tests were performed using allele-specific real-time polymerase chain reaction in pooled venous blood samples. The mutation was found in 8 (0.65%) samples from 5 men aged 31—52 years. The allelic load of the mutant gene was 0.07—2.6%. Four of the five mutation carriers had been donors for 7.5—13 years and had made 16 to 90 donations each. Only one of the five men had developed hematological changes characteristic of polycythemia that caused to refrain him from donations. Ability of the mutant clones to form the erythropoietin-independent colonies in vitro and generate foci of extramedullary proliferation raises the concern about safety of blood transfusions and bone marrow transplantations from donors carrying the JAK2 V617F mutation. Whether the frequency of blood donations increases the risk of somatic mutations in JAK2 is a question that requires further studies.

The juvenile nasal angiofibroma (JNA) surgeries are very often complicated by massive intraoperative blood loss. In order to compensate it the intraoperative blood reinfusion of autologous erythrocytes from operative field by cellsaver is very often used. But the high probability of chronic inflammation of blocked sinuses in patients with JNA raised the question of possible bacterial contamination of reinfused blood. In this context we have carried out the bacterial tests of blood samples of different steps’ cell-saver recycling in 11 patients with JNA during 12 surgeries and analized the bacterial status of sinuses in 7 of them. The bacterial contamination was confirmed by the following growth of hemoculture in 11 out of 12 observations. None of our patients was diagnosed with symptoms of generalization of contamination or sepsis in the postoperative period.

The prothrombin complex concentrates (PCCs), containing therapeutic doses of vitamin K-dependent coagulation factors, were licensed for reversal of vitamin K antagonist therapy. However, recently clinicians sought to use PCCs for any number of off-label indications. The goal of this review is to explore practical issues regarding PCCs. Specifically, aims are to examine the role of PCCs in vitamin K antagonist reversal, review its potential use in the treatment of hemorrhage due to direct oral anticoagulants, and explore potential uses in liver disease, trauma-associated bleeding, etc. Safety and other practical considerations of PCCs will also be discussed.

The pseudotumors are the serious complication in patients with hemophilia A and B. Surgical excision of hemophilic pseudotumor is frequently accompanied by a massive intraoperative blood loss. The endovascular embolization of the feeding arteries prior to surgery helps to minimize the blood loss and to reduce the size of pseudotumor. We performed endovascular embolization with microcoils in six hemophilia patients with pseudotumors, and describe here three of those cases.