[CHANGE OF ANTICOAGULANT EFFECT OF RIVAROXABAN DURING A DAY].

The article presents an assessment of anticoagulant effect of rivaroxaban in 35 patients with thromboembolic diseases. The results of expressed anticoagulant effect of rivaroxaban were obtained during a day (or more). The data of increase in sensitivity to thrombomodulin indicated about work enchancement of protein C system against the background of rivaroxaban therapy.

[Use of thrombin generation assay for the evaluation of coagulation and anticoagulant activity of hemostasis system in patients with abdominal sepsis].

Generally recognized factor, which complicates the course of sepsis, is the development of hypercoagulation syndrome. The increase of thrombin coagulation indicates on the elevation of risk of thrombus formation in microcirculation vessels, which could cause the formation of multiple organ failure. The thrombin generation assay is a new method of the evaluation of homeostasis system status. The test reflects the fermentation activity of thrombin and shows the functional condition, which arises in the interaction of procoagulant and anticoagulant. The diagnosis of generalized peritonitis had 30 patients (18 men and 12 women, aged 61+/-18,3 years) and they were included in the research. It was shown, that the use of thrombin generation assay in patients with the abdominal sepsis could give the well-timed analysis of hypercoagulation changes and the assessment of protein C system investment in the thrombin generation.

[Assessment of endogenous thrombin potential and influence on it of different regimens of heparin therapy in patients with abdominal sepsis].

Abdominal sepsis (AS) is a systemic inflammatory reaction of organism in response to the development of infectious process in organs of the abdominal cavity. The course of AS is complicated by hypercoagulation syndrome which facilitates progression of endogenous intoxication. The investigation included 26 patients (14 men and 12 women, mean age 65.5 +/- 16.4 years) with AS. The test of thrombin generation (TTG) used in patients with AS allows assessment of changes in the hemostasis system and control of the heparin dose. It was established that TTG revealed elevated endogenous thrombin potential of blood practically in all patients with AS. In the patients given 25 000 IU of heparin the TTG indices showed a reliably decreased endogenous thrombin potential and peak thrombin concentration as compared with a group of patients given 10 000 IU of heparin.

[The conditions of arrangement of the thrombin generation test to detect the hypercoagulation status].

The study covered the impact of modes of preparation of plasma samples to arrange the thrombin generation test for the purpose to establish adequately the hypercoagulation status. The optimal regimen is determined to prepare the samples to be used in the study. The group of females was involved into the study to take the composite oral contraceptives to demonstrate the possibility to apply the thrombin generation test to reveal the hypercoagulation.

[Genetic determinants of hereditary thrombophilia in pathogenesis of venous thrombosis]. / Geneticheskie determinanty nasledstvennoi trombofilii v patogeneze venoznogo tromboza.

AIM: To study the role of genetic determinants of hereditary thrombophilia in pathogenesis of various clinical manifestations of venous thrombosis in the citizens of the North-West Region of Russia. MATERIAL AND METHODS: Mutations of the genes of factor V (FV Leiden), prothrombin (G20210-A) and polymorphism C677-T in the gene of methylentetrahydrofolate reductase (MTHFR) were detected using polymerase chain reaction (PCR) with a following restriction analysis of PCR product in 183 patients with venous thrombosis (115 with isolated thrombosis of the deep veins and 68 with thromboembolism of the pulmonary artery). RESULTS: It was established that mutation FV Leiden is a significant risk factor of deep vein thrombosis in the legs and postthrombotic disease, but this mutation is weakly associated with pulmonary artery thromboembolism (PAT). An essential PAT risk factor is carriage of the variant prothrombin G20210A. CONCLUSION: Determination of prothrombotic genotypes is a key factor of treatment efficacy and prevention of life-threatening thromboembolic complications.

[Changes in hemostasis system in patients with hereditary thrombophilia caused by mutation of blood coagulation factor V ( factor V Leiden)]. / Izmeneniia v sisteme gemostaza u bol'nykh s nasledstvennoi trombofiliei, obuslovlennoi mutatsiei faktora V svertyvaniia krovi (faktor V Leiden).

AIM: To study the incidence of mutation of Leyden's factor V in patients with venous thrombosis and the hemostatic system in carrier of this genetic defect. MATERIALS AND METHODS: A hundred and one patients aged 15-69 years who had venous thrombosis and 10 individuals with mutation of Leyden's factor V without manifestations in the history of thrombosis were examined. Factor V gene mutations and the thrombocyte and plasma links of hemostasis were determined by routine methods. RESULTS: The Leyden's factor V genotype Arg506-->Gln was detected in 17 of the 101 patients with venous thrombosis. Patients and asymptomatic individuals with this factor were found to have significant hypercoagulation, as evidenced by lower activated protein C-resistance index, higher factor VIII (von Willebrand's factor) activity, elevated von Willebrand's factor antigen levels, and enhanced intravascular platelet activation. In the presence of lupoid anticoagulant, hypercoagulation increased and protein C activity decreased. CONCLUSION: Detection of signs of hypercoagulation in patients with inherited thrombophilia at recovery in carriers of Leyden's factor V without clinical manifestations of thrombosis shows it necessary to make a particularly careful monitoring of the hemostatic system in these subjects. This is especially important for hypercoagulation-predisposing situations, such as pregnancy, surgical interventions, long-term immobilization, use of contraceptives, etc. when preventive measures may be used to prevent thrombotic events.

[The megakaryocyte-thrombocyte system]. / Sistema megakariotsit-trombotsit.

The megakaryocytic apparatus of bone marrow and platelets are discussed as a common system whose physiological purpose is to ensure hemostasis when the integrity of the vascular wall is impaired. The principle of operation of the megakaryocyte-platelet system is synthesis, accumulation, and organization of a potent hemostatic potential, its distribution and dispersal along the vascular bed, if inactive, and its new formation at the moment of and at the site of required hemostasis. At the same time in its early and late major functional performance, the elements of the system are stable-at the early stages of megakaryocytopoiesis to the extent to the appearance of a promegakaryocyte and at the stage of platelet hemostatic cork. At the intermediate stages-that of the mature megakaryocyte divided by demarcation membranes and that of reversible aggregation of platelets which have not lost their individuality, the elements of the system are in an unstable state that is ready for disintegration or in a state that does not exclude its possibilities. In the central phase of its existence, the system is in a disintegrated state and appears as proplatelets and platelets. The mechanism of the dispersal and combination of elements and hemostatic potential of the megakaryocyte platelet system serves the apparatus of structural and contractile proteins, which acts as its system-forming factor.

[The diagnostic characteristics of von Willebrand's disease]. / Osobennosti diagnostiki bolezni Villebranda.

70 patients from 48 families were examined. Of them, 59 (84%) patients had type I Willebrand's disease (WD), 9 (13%) type II, 2 (3%) type III WD. Hemostasis was assessed by functional tests: APTT, FVIII activity, bleeding time, ristocetin-cofactor activity of plasma Willebrand factor (WF). The WF levels in plasma and platelets were measured on a Reader-210 Microwell system by enzyme immunoassay with 380 F2 monoclonal antibodies to human WF. The functional parameters in 65 patients in remission were within normal range in half the patients. The only objective diagnostic criterion of the patients inclusion into WB group was the level of WF in plasma, especially when patients with type I WD were examined. The level of WF was always low in patients of this group even in the presence of normal values of functional tests. The severity of WD course and definition of laboratory signs of the disease depended mainly on the involvement of platelet WF in pathological process. In patients with a decrease of both plasma and platelet WF the course of the diseases was most serious and laboratory data most shifted from normal.

[Immunoenzyme method of determination of Willebrand's platelet factor]. / Immunofermentnyi metod opredeleniia trombotsitarnogo faktora Villebranda.

A method for Willebrandt factor antigen measurement in platelets has been developed based on indirect solid-phase enzyme immunoassay with monoclonal antibodies. The mean platelets Willebrandt factor level in 17 normal subjects was 21.5% (S = +/- 8.88; S mean = 2.16%). The method was tried in a group of patients with Willebrandt's disease. A relationship was demonstrated between Willebrandt platelet factor level and the degree of disorders in hemorrhage duration.

[The locomotor-contractile system of thrombocytes--an optimal model for studying the physiological motor and contractile processes in the effector systems of the non-muscular cells]. / Oporno-sokratitel'naia sistema trombotsitov--optimal'naia model' dlia izucheniia fiziologicheskikh dvigatel'nykh i sokratitel'nykh protsessov v éffektornykh sistemakh nemyshechnykh kletok organizma.

The authors suggest a concept according to which the cytoskeleton and contractile proteins of platelets are the locomotor-contractile system playing a role of the effector apparatus of hemostatic function of these cells. Demonstrate the role of the contractile structures in leukocyte phagocytosis.

[Methods of isolating intact thrombocytes from blood]. / Metody vydeleniia iz krovi intaktnykh trombotsitov.

A combined method of platelet isolation in albumin density gradient followed by gel filtration through a column packed with Sepharose 2B appears to be the best for the isolation of intact platelets free from plasma proteins, fit for research purposes; for clinical studies a more available technique for intact platelet isolation in albumin density gradient is recommended.

[Variant forms of von Willebrand's disease]. / Variantnye formy bolezni Villebranda.

Abnormalities of platelet and plasma Willebrand's factor produce noticeable effects on the clinico-laboratory manifestations of Willebrand's disease. This is confirmed by more pronounced gravity of the hemorrhagic syndrome, the lack of the correcting effect in response to physiological conditions (pregnancy) and administration of DDAVP in contrast to beneficial effect seen in patients with normal content of Willebrand's factor in platelets.

[Immunoenzyme analysis of the Willebrand factor using monoclonal antibodies]. / Immunofermentnyi analiz faktora Villebranda s ispol'zovaniem monoklonal'nykh antitel.

A method for measuring Willebrand's factor protein has been developed, based on indirect solid-phase enzyme immunoassay with Soviet monoclonal antibodies to this factor. Normal Willebrand's factor level in the plasma has been found 55-161 percent. The method has been tried in patients with Willebrand's disease and with oncologic diseases.