Aim: to study the contribution of maternal blood endothelial proteins to developing relapse of early preeclampsia (ePE).Materials and Methods. A proteomic analysis of the peripheral blood of 137 pregnant women was performed. Clinically, three groups were identified at the end of pregnancy: control (n = 40), patients with favorable course of the current and previous pregnancy; comparison group (n = 59) – patients with a history of еPE episode, but favorable course of ongoing pregnancy, and main group (n = 38) – patients with еPE relapse. Biologically active substances evidencing about impaired endothelial function were subject to dynamic monitoring (11–13, 19–21 and 27–28 weeks): activity of endothelin-1 (ET-1) and metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), von Willebrand factor (vWF) level and homocysteine (HC) concentration. The ADAMTS-13/vWF ratio was evaluated separately.Results. For patients with recurrent еPE, a significant increase in ET-1 is characteristic at all stages of gestation: 0.92; 1.07 and 1.36 pmol/ml vs. 0.29; 0.33 and 0.29 pmol/ml in the control group (p < 0.0001 at all points). Regardless of pregnancy outcome, increasing gestational age was paralleled with elevating vWF level, however, upon еPE relapse, this parameter (Me = 343 IU) is significantly higher (p < 0.0001) than in control group (Me = 260 IU). In all groups, there was a significant decrease in ADAMTS-13 activity, whereas in main group ADAMTS-13 activity at first time point was minimal – 63.4 % (p = 0.0007 relative to control group). With regard to ADAMTS-13/vWF axis in relapsed еPE, significant differences were found compared with control group both at 11–13 weeks (0.32 vs. 0.52; p < 0.0001) and at 27–28 weeks (0.15 vs. 0.22; p < 0.0001) pregnancy. The HC concentration declines with gestational age, but at first time point patients from main group had it (Me = 8.0 µmol/L) at significantly higher level than in control group (Me = 5.9 µmol/L; p < 0.00010).Conclusion. At gestational age of 11–13 weeks, all analyzed biomarkers contribute to developing еPE relapse accounting for an overall impact of 62.3 % of developing ePE risk. During pregnancy at 19–21 weeks, an imbalance in the ADAMTS-13/vWF along with elevated ET-1 level determine the risk of disease relapse in 65.6 % of cases. It was found that at a gestational age of 27–28 weeks, the associated shift in ET-1, vWF and ADAMTS-13 magnitude accounts for 67.9 % of risk for disease relapse.

Aim of the study was to evaluate the effect of lithium- and melatonin-containing sorbent based on aluminum oxide and polydimethylsiloxane on changes in the number of platelets during hemosorption modeling and on the features of the hemostatic response during dosed contact of the sorbent with blood in an in vitro experiment. Material and methods. An analysis of the effect of the porous sorbent modified with melatonin (MT, 0.15 %) and lithium (0.5 %) based on aluminum oxide and polydimethylsiloxane (Al2O3@PDMS/MT-Li) was carried out in comparison with sorbent without modifiers (Al2O3@PDMS) and modified with MT (Al2O3@PDMS/MT) on a number of donor blood clotting parameters under in vitro hemosorption conditions. Studies of the hemostatic system included assessment of platelet count, chronometric parameters, fibrinogen concentration, antithrombin activity and plasminogen content. For integral assessment, calibrated thrombography and computer thromboelastometry were used. Results and discussion. Contact of all studied sorbents with blood causes a moderate decrease in the number of platelets (by 5.3–10.1 % from initial). Comparison sorbents reduce fibrinogen concentration by 7.1–7.7 %, Al2O3@PDMS/MT-Li – by 2.6 times, which is likely due to the methodology for determining this protein against the background of the independent anticoagulant activity of lithium ions. Al2O3@PDMS and Al2O3@PDMS/MT cause the development of a hypercoagulable shift, as evidenced by a shortening of kaolin time (by 27.5 and 22.1 %, respectively) and of activated partial thromboplastin time (APTT) by 7.1 % for both sorbents. At the same time, when lithium was included in the sorbent, not only did the hypercoagulation shift not occur, but blood clotting was also inhibited, as evidenced by an increase in kaolin time and APTT by 1.2 and 1.6 times, respectively, as well as in silicone time. Conclusions. Modifying sorbents with biologically active substances, lithium and MT, makes it possible to obtain an original hemosorbent with new properties. The presented results demonstrated the absence of a hypercoagulable shift in donor blood after contact with a lithium-, MTcontaining sorbent in vitro and indicate the potential for its using as a basis for the development of safe drugs.

This article presents the results of a study of the systemic hemostatic action of recombinant Factor VIIa in a rabbit model of heparin-induced coagulopathy and posttraumatic bleeding, compared to the administration of exogenous fibrin monomer. The coagulopathy was induced by a single intravenous injection of unfractionated heparin at a dose of 150 IU/kg 15 minutes before injury. Recombinant Factor VIIa (270 μg/kg) or fibrin monomer (0.25 mg/kg) was used as systemic hemostatic agents. One hour after administrating the agents, a standardized liver injury was inflicted, followed by an assessment of blood loss characteristics. Using rotational thromboelastometry and coagulation tests, animal venous blood was analyzed for coagulation time, alpha angle, clot formation time, maximum clot firmness, clot density at 10 minutes, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen concentration. Pharmacologically induced coagulopathy resulted in shifts to a hypocoagulable profile, associated with severe blood loss (1.9 times, p = 0.028) and high animal mortality (26.1%, p = 0.022) compared to the control group. Preventive administration of fibrin monomer or recombinant Factor VIIa reduced posttraumatic blood loss (by 5.4 times, p 0.001, and by 2.1 times, p = 0.009, respectively), resulting in a decrease in mortality rates. However, the administration of these agents did not correct the hypocoagulable profile as observed in thromboelastometry and coagulation tests. These data demonstrate the hemostatic effect of both agents, with a more pronounced effect after fibrin monomer administration, and suggest potential use of low doses of fibrin monomer in trauma-related hemorrhage. The mechanism of action of fibrin monomer requires further investigation. Therefore, fibrin monomer, a fibrinogen derivative obtained from blood plasma, could be a valuable candidate for managing wound bleeding in addition to recommended systemic hemostatics.

Introduction. The outbreak of the novel viral infection SARS-CoV-2 and its associated pandemic has generated significant interest among professionals regarding the role of D-dimer as a marker. D-dimer not only reflects the intensity of hemostatic and fibrinolytic reactions but also holds prognostic value. However, the standardization of D-dimer determination remains elusive, as the findings are known to depend on the completeness of fibrinolysis in the vasculature. Objective. This study aims to investigate the objective values of D-dimer levels, taking into consideration the concentration of its terminal fragments in plasma, specifically in patients with intravascular thrombosis associated with coronavirus infection. Materials and Methods. The study involved the examination of sodium citrate-stabilized plasma from 90 patients with severe COVID-19 who required respiratory support upon admission to the intensive care unit (ICU). The ICU mortality rate was 50% within 14 days. Additionally, a control group of 78 healthy individuals was included. The quantitative determination of D-dimer in human plasma was conducted using the Auto Red D-Dimer 700 (Helena Bioscience) and Sysmex CA1500 coagulation analyzer (Sysmex Corporation). Fibrinolysis was stimulated in vitro by streptokinase during sample preparation. The assessment was based on the analysis of blood plasma before and after the administration of the fibrinolysis activator. Results. Using the classical method of determination, D-dimer levels exceeded the cut-off value (300 ng/ml) in 61 out of 90 patients (67.8%). After fibrinolysis stimulation with streptokinase, this number increased to 66 (73.3%). Compared to the survival group, the fatal outcome group exhibited a 143.6% higher D-dimer level using the classical approach (p=0.2355). With the new approach involving streptokinase, the increase was 181.2% (p=0.0257). In one-fifth of fatal cases, the streptokinase-induced D-dimer concentration was more than twice the baseline obtained through the classical approach. Conclusion. The proposed approach for quantitatively determining D-dimer, which incorporates the use of streptokinase, provides more accurate data regarding the plasma concentration of D-dimer neoantigens. These findings establish a potential direction for standardizing such studies in clinical practice, particularly for determining treatment strategies for patients with COVID-19.

The effects of a lithium-modified sorbent based on aluminum oxide and polydimethylsiloxane (Al2O3@PDMS/Li) and a lithium-free sorbent (Al2O3@PDMS) on some indicators characterizing blood clotting under hemosorption conditions were compared in vitro. Sorbent Al2O3@PDMS/Li had significantly lower reactogenic effect on the blood passed through the column than the sorbent without lithium. This was seen from the degree of platelet reduction (66×109 vs 19×109/liter) as well as a less pronounced hypercoagulation shift in chronometric indicators. In contrast to lithium-free sorbent, Al2O3@PDMS/Li demonstrated the ability to reduce the concentration of fibrinogen. However, this had no impact on the density characteristics of the blood clot assessed by thromboelastometry such as maximum clot firmness, angle and fibrin clot formation time, amplitudes at 10 and 15 min after clotting time, which are known to depend on the quantity of platelets and the concentration of functionally active fibrinogen.

Background. In our previously published studies, we demonstrated a high hemostatic activity of a low dose of exogenous fibrin monomer during its systemic administration in a model of dosed liver injury with preliminary inhibition of platelet aggregation. However, the analysis of platelet involvement in the mechanisms of local fibrin formation has not been analyzed. The aim of the study. To conduct a comparative analysis of the cellular composition of venous and wound blood, as well as blood in the wound vessels to assess the contribution of platelets to the hemostatic effect of exogenously administered fibrin monomers in dosed liver injury under conditions of pharmacologically determined thrombocytopathy. Methods. In a model of dosed liver injury in rabbits after inhibition of platelet aggregation by acetylsalicylic acid in combination with clopidogrel, the effect of the administration of fibrin monomer was evaluated in comparison with the use of tranexamic acid. We studied the number of platelets in venous and wound blood smears, as well as in the contents of wound vessels. Results. It has been established that with the systemic administration of exogenous fibrin monomer, the number of platelets in wound blood smears decreases by 17.2 % in comparison with free circulating venous blood. Platelets in wound blood form aggregates and are in an activated state. In the wound vessels, the number of these cells was maximum (150 per lower field) compared with the number of platelets in the placebo and tranexamic acid groups (55 and 84 per lower field, respectively). Also in the wound blood, erythrocytes with altered forms (echinocytes, schistocytes, stomatocytes and ovalocytes) were found. Conclusion. Systemic administration of exogenous fibrin monomer affects the redistribution of platelets between the systemic circulation, wound vessels and wound blood, determining its hemostatic effect and local wound fibrin formation in dosed liver injury. The presence of receptor-mediated platelets recruitment due to fibrin monomer in the wound vessels with the participation of damaged erythrocytes is assumed.

Introduction. Platelet dense granule disorders are a group of rare heterogeneous disorders of the blood coagulation system in which bleeding occurs due to functional and morphological disorders of platelet organelles accumulating phosphates and bioactive amines. Aim - to present a clinical case of a 37-year- old patient with severe hemorrhagic syndrome. Basic information. An observation of the occurrence of hemorrhagic manifestations of unspecified genesis in a patient is described. The results of 25 healthy volunteer examinations of both sexes were used as a control for testing methods of diagnosis of Platelet dense granule disorder. Methods of assessing the hemostasis system, platelet morphological features using electron microscopy, as well as platelet accumulation of mepacrine using a flow cytometer were studied. Platelet dense granule disorder was detected by electron microscopy and confirmed by flow cytometry in a patient with severe hemorrhagic manifestations, in whom the diagnosis was not verified for a prolonged period of time.

INTRODUCTION: Earlier, an ability of exogenous fibrin monomer (FM) introduced at low doses to considerably limit posttraumatic blood loss was established by us on an experimental model of warfarin coagulopathy in vivo. However, the morphologic peculiarities of fibrin formation in the wound area were not considered. AIM: To compare morphologic, hemostasiologic and hemostatic data based on the results of systemic application of exogenous FM to interpret their effects in the model of posttraumatic bleeding with the underlying intake of warfarin. MATERIALS AND METHODS: In the work, Chinchilla male rabbits were used. A comparative analysis of hemostasiologic effects and of morphologic picture of the surface of the liver in the wound area was conducted after a dosed trauma, with a preliminary systemic introduction of FM (0.25 mg/kg intravenously) or a concentrate of prothrombin complex factors (40 IU/kg intravenously) with the underlying intake of warfarin by animals (0.40.5 mg/kg/day per os for 2 weeks). RESULTS: Introduction of FM in warfarinised animals in the conditions of a dosed experimental liver injury promoted a hemostatic effect comparable with that of a concentrate of prothrombin complex factors. Both hemostatic drugs led to intense fibrin formation that reduced posttraumatic blood loss. The use of FM was associated with increase in the thickness of thrombotic deposits and fibrin fibers in the wound surface in comparison with placebo by 4.0 and 1.6 times, respectively (р 0.000001). This process actively involved platelets, which led to 1.7 times reduction of their quantity in the lumen of the blood vessels in the wound vicinity (р 0.0002). No effect of FM on systemic hemostatic reactions in venous blood was found, in contrast to concentrate of prothrombin complex factors. CONCLUSION: Exogenous FM can produce a local hemostatic effect in the conditions of dosed experimental trauma and coagulopathy induced by warfarin intake. The hemostatic effect was mediated by intense thrombosis on the wound surface with the active recruitment of platelets in the process. The peculiarities of the demonstrated effects of FM may be mediated though the mechanisms of its action that have not yet been identified, which necessitates continuation of the research in this direction.

INTRODUCTION: Despite the progress in understanding the pathophysiology of coagulopathy in COVID-19, data about the association and phasing of pathological changes in various parts of the hemostatic system with the development of acute respiratory distress syndrome (ARDS) are insufficient. OBJECTIVE: To determine association between the severity of respiratory failure and pathological changes in the hemostatic system in COVID-19 patients. MATERIALS AND METHODS: A prospective observational study included 204 patients with a confirmed diagnosis of severe and extremely severe COVID-19. Two groups were identified according to disease outcome: fatal (n = 106) and survived (n = 98) groups. To assess dynamics of the clinical picture of the disease and to study the hemostatic profile, time points were determined: I point — the first day — admission to intensive care unit; II point — 3–5 days, III point — 7–10 days after ICU admission. The respiratory index was calculated to assess the severity of respiratory distress syndrome. Statistical data processing was carried out using the statistical software package MedCalc Version 20.110 (MedCalc Software Ltd, Belgium). RESULTS: A 2.15-fold decrease in the respiratory index was determined for fatal outcome in patients with severe and extremely severe COVID-19. The most important hemostatic parameters affecting the severity of respiratory failure are increased Willebrand factor concentration at I point of the study (21 % contribution and inverse correlation), increased plasminogen activator inhibitor type 1 (PAI-1) level on 3–5 days (35 % contribution and direct correlation), and activation of the coagulative component of hemostasis on 7–10 days (78 % contribution and direct correlation). CONCLUSIONS: The severity of respiratory failure in patients with a confirmed diagnosis of severe and extremely severe COVID-19 is gradually associated with endotheliopathy (1 day), inhibition of parietal fibrinolysis (3–5 days) and activation of the coagulative component of hemostasis by 7–10 days of ICU stay.

Отличительной чертой новой коронавирусной инфекции (НКИ) COVID-19 является быстрое развитие коагулопатии с формированием тромбозов, которые поражают не только магистральные сосуды, но и систему микроциркуляции. Патогенез COVID-19-ассоциированных тромбозов многообразен и индивидуален. «Золотого» стандарта диагностики COVID-19-ассоциированных тромбозов в настоящий момент установить не удалось. Основным методом профилактики и лечения COVID-19-ассоциированных тромбозов является терапия антикоагулянтами. Нет надежных доказательств целесообразности применения антиагрегантов в комплексе мер тромбопрофилактики при НКИ COVID-19. Тромболитическая терапия является таргетным методом лечения COVID-19-ассоциированных тромбозов. В настоящий момент имеется опыт ее применения «off-label», проводятся клинические исследования, но клинические рекомендации по применению тромболитической терапии больных НКИ COVID-19 пока отсутствуют. COVID-19 is distinguished by the rapid development of coagulopathy associated with thromboses that affect both the main vessels and microcirculation. The pathogenesis of COVID-19-related thrombosis is diverse and individual, while the gold standard for its diagnosing has not yet been established. The main method for COVID-19-related thrombosis prevention and treatment is anticoagulant therapy. There is no reliable evidence for the use of antiplatelet agents in thromboprophylaxis for COVID-19. Targeted treatment in COVID-19-related thrombosis is thrombolytic therapy that is now used off-label. Clinical studies are being conducted; however, clinical recommendations for its use in patients with COVID‑19 are not yet available.

Relevance. The basis of the complex, in some cases, of interrelated pathological processes in opisthorchiasis invasion may be endothelial dysfunction, which provokes the risks of cardiovascular events, and is an important aspect in establishing pathogenetic connections between diseases of the liver and the cardiovascular system. When assessing the inflammatory process in the pathogenesis of invasion, there is increasing interest in the contribution of not only cellular elements and circulating inflammatory markers, but also in intercellular communication and regulation through microvesicles. Purpose of the study. To study the circulation of extracellular vesicles, which are associated with blood and endothelial cells, in patients with chronic opisthorchiasis. Materials and methods. The study was conducted on two groups of people (men and women aged 18 to 55 years (34.3±1.3 years)). The experimental group included patients with chronic opisthorchiasis (n=26). There was the control group (n=14) matched by gender and age with experimental group. The qualitative composition and quantity of extracellular vesicles (EVs) was determined by flow cytometry. Results. In the experimental group, there was a significant increase in the number of CD41+ events (platelet EVs) 2 times (from 120 to 245 events/μl (p = 0.030), CD45+ events (panleukocyte EVs) - more than 120 times (from 95 to 11713 events/μl (p=0. 0330), as well as a trend towards an increase in the rate for CD31+ events by 19.8 times (from 495 to 9818 events/μl (p=0.133) in comparison with control group. Screening assessment of the CD9+ population of platelet EVs (CD41+31+CD9+), endothelial EVs (CD41-31+9+) and leukocyte EVs (CD45+CD9+) showed a significant (p=0.0330) increase in events, while their content corresponded to the data obtained by CD31+41+ events in quantitative terms. For endothelial EVs, there was a significant increase in the proportion of CD9+ events from 23.3% in the control to 46.2% in the experimental group, while for leukocyte EVs there was no statistically significant change in the percentage ratio, and it was 9.9% in the control and 12.9% in the experimental group. Conclusions. These results can be considered from the perspective of platelet activation, as well as the development of the inflammatory process and endothelial dysfunction, where microvesicles can act as potential highly sensitive markers for opisthorchiasis invasion.

Hemosorbents used in medicine must be safe in relation to blood cells, especially to easily vulnerable platelets. The aim of this work is to study the effect of sorbents with single-walled carbon nanotubes Al 2 0 3 @ PDMS/SWNT in comparison with carbon-free sorbent Al 2 0 3 @PDMS on hemostatic reactions. The study of physicochemical properties of sorbents was carried out according to standard methods. The biological properties of the sorbents were evaluated by their effect on the platelets of donor blood. The data obtained in vitro experiments revealed a decrease in the number of these cells after blood contact with both sorbents and a glass column not filled with sorbent, but both studied sorbents neutralized a hypercoagulation shift in a number of coagulogram parameters due to blood contact with a glass column. The introduction of carbon in the form of single-walled carbon nanotubes in an amount of 0.02 % into the sorbent composition enhances the sorption properties by 40 times in relation to the sorption of a marker of high-molecular molecules (vitamin B12) and is comparable in terms of the sorption of low-molecular markers (methylene blue dye) compared to a sorbent without nanotubes. The data obtained allow us to conclude that new carbon sources can be used to obtain carbon-mineral sorbents.

Evaluation of the hemostatic effect of thrombin formulated in monocomponent dosage forms and combined coatings based on a natural polymer, bacterial cellulose, was an important stage for us in the development of new local hemostatic agents. In vivo and in vitro studies of thrombin preparation in powder and solution forms in various doses (150, 375, 750, and 1500 NIH units), as well as coatings based on bacterial cellulose and thrombin administered into their structure, were conducted. All monocomponent powder formulations of thrombin analyzed were found to have high hemostatic properties. Increasing the dosage of thrombin 2 and 4 times, starting with 375 NIH units, did not lead to a significantly increased hemostatic activity, and the hemostatic effect of the solutions was less than that of powders with a similar level of this enzyme. Thrombin administered to the structure of the coatings does not significantly increase their hemostatic activity; however, it causes a hypercoagulation change according to the findings of in vitro experiments.

Цель. Оценка гемостатической активности локальных покрытий в форме губки на основе различных полисахаридов природного происхождения in vitro.

Aim: to assess the blood level of biological endothelial damage markers in women with previous early-onset preeclampsia (еPE) during both the preconception (PC) stage and the first trimester of pregnancy. Materials and Methods. A prospective single-center cohort study was conducted. The control group comprised 40 women with uncomplicated pregnancies. The observation group consisted of 97 patients with a history of ePE, stratified based on pregnancy outcome into the comparison group (n = 59) characterized by a favorable gestational course, and the main group (n = 38) with relapsed еPE (30 patients were excluded from the study). Markers of systemic endotheliosis were determined in women at the PC stage and at 11–13 weeks of gestation: endothelin-1 (ET-1) and endothelial extracellular vesicles (EVs; CD-144). Results . At the PC stage, women in the control group and patients from the comparison group had comparable median (Me) ET-1 levels – 0.39 and 0.40 pmol/ml (p = 0.5935), respectively; at the same time, patients with relapsed еPE vs. control group had it significantly elevated (Me = 0.55 pmol/ml; p = 0.0382). At gestational age of 11–13 weeks, ET-1 level was significantly higher in the group with relapsed еPE (Me = 0.93 pmol/ml) than in control group (Me = 0.29 pmol/ml; p < 0.0001) and comparison group (Me = 0.42 pmol/ml; p = 0.0003). No significant changes in E-EVs (CD-144) level at various PС stages were observed, whereas in the study groups such parameters remained differed. Conclusion . Biological markers evidencing about systemic endothelial dysfunction/destruction – ET-1 and E-EVs (CD-144) in patients with previous ePE can be considered as predictive tests of disease relapse with an accuracy of 63.5 % and 83.0 % at the PС stage and 85.7 % and 94.2 % at gestational age of 11–13 weeks, respectively.

СОХРАНЯЮЩАЯСЯ ДИСФУНКЦИЯ ЭНДОТЕЛИЯ У ПАЦИЕНТОК С РАННЕЙ ПРЕЭКЛАМПСИЕЙ

The objective: to study the relationship between markers of imbalance in the platelet-vascular hemostasis system and lung damage and disease outcome in patients with COVID-19.Subjects and Methods: the study included 225 patients with the confirmed diagnosis of moderate, severe and extremely severe COVID-19. In all patients, lung damage was confirmed using computed and X-ray diagnostic methods. We studied the concentration of von Willebrand factor (vWF), activity of metalloproteinase ADAMTS-13, concentration of homocysteine, endothelin-1, thrombomodulin and the number of platelets and changes in these parameters on the 1st, 3–5th and 7–10th days from the admission to the intensive care unit (ICU). In deceased patients (n = 106), lung specimens were collected to assess the nature of morphological changes.Results. It was determined that by the 7–10th days with a lethal outcome of the disease, there was a statistically significant increase in the concentration of vWF by 22.2% (p = 0.0225), the vWF/ADAMTS-13 ratio by 2 times (p = 0.0408) and decrease in the platelet count by 52% (p = 0.0008) versus the initial stage of the study. In all the deceased, the morphological picture of lung tissue damage was characterized by destruction of alveolocytes, proliferation of connective tissue, cellular infiltration, plethora of capillaries, parietal erythrocyte thrombi in the lumen of capillaries, arterioles and venules, and obstructive erythrocyte thrombi in the lumen of vessels of lung microcirculation.Conclusion. The study showed that a possible cause of thrombosis in the lumen of vessels of lung microcirculation in the case of a lethal outcome of COVID-19 might be a primary imbalance in the vascular-platelet hemostasis characterized by a significant increase in the concentration of the vWF factor, the vWF/ADAMTS-13 ratio and a decrease in the number (consumption) of platelets by the 7–10th day of the disease versus the initial stage of the study.

Цель. Анализ свойств покрытий на основе модифицированной бактериальной целлюлозы и сравнение их структуры, гемостатической активности и физико-химических свойств с покрытиями из немодифицированной бактериальной целлюлозы.

Aim. To compare predisposition to thrombosis caused by administration of known systemic hemostatic agents and fibrin monomer under the conditions of normal coagulation versus drug-induced hypocoagulation in the experiment. Materials and methods. The prothrombotic effect of intravenous (IV) administration of various systemic hemostatic agents was compared in a series of in vivo experiments. These agents included fibrin monomer (FM) (0.25 mg / kg), prothrombin complex concentrate (PCC) (40 IU / kg) or recombinant factor VIIa (rFVIIa) (270 mcg / kg). The studies were conducted under the conditions of hypocoagulation induced by the administration of warfarin ( per os at a dose of 0.4–0.5 mg / kg / day for 14 days) or dabigatran etexilate ( per os at a single dose of 15–20 mg / kg). Hemostatic system parameters were evaluated using thromboelastometry and calibrated automated thrombography. Results. It was found that PCC reversed anticoagulant effects and led to an overcompensated increase in the density characteristics of the blood clot along with an excessive increase in thrombin generation in the groups of animals with warfarin-induced coagulopathy. The use of PCC and rFVIIa in the groups of animals with dabigatran-induced hypocoagulation also resulted in an increase in blood thrombogenic properties. In the administration of PCC, it was manifested though an increased D-dimer level and in administration of rFVIIa – through an increase in the clot density characteristics. At the same time, replacement of these hemostatic agents with FM did not affect the hemostatic system parameters. Conclusion. FM at a dose of 0.25 mg / kg, as opposed to PCC and rFVIIa, is safer in terms of the risk of thrombosis.