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The article discusses the evolution of the endovenous laser ablation technique for the treatment of varicose vein disease of lower extremities. The history of studies aimed at improving the endovenous laser ablation is provided. The authors described the features of endovenous laser ablation with wavelengths from λ = 0.445 to 1.94 µm, alongside with edge- and radial-emitting working fibers, as well as fibers with radiation absorption at its distal end. The physical and biophysical mechanisms of the most popular to-date method for outpatient treatment of varicose vein disease of lower extremities are reviewed. The propagation process of laser radiation in the scattering medium is described, and the important role of the radiation scattering effect on the depth of its penetration into biological tissues is shown. The processes that take place during endovenous laser ablation are considered. The difference in physical processes that take place during the use of laser radiation mainly absorbed by hemoglobin (hemoglobin-absorbed range) and by water (water-absorbed range) is described. Expedience of simulating the processes that take place during endovenous laser ablation with the use of blood plasma has been substantiated. The blood plasma simulation demonstrated the decisive action of laser-induced boiling on thermal damage to the vein wall, which causes its fibrous transformation. It has been shown that the use of radial-emitting fibres during intense boiling generates steam bubbles around the site of radiation coupling. The contents of such steam bubbles do not absorb radiation, which thus reaches the venous wall, causing its symmetrical thermal damage. The advantages of using water-absorbing radiation with a wavelength of λ = 1.94 µm in conjunction with a radial-emitting fibre have been substantiated.

Background: At the present moment, an urgent and unresolved problem is the search for a method to diagnose disorders of the hemostasis system in patients with the new coronavirus infection. The integral tests, in particular, the thrombodynamics test, will presumably make it possible to monitor changes in blood clotting, and predict the course of the disease in patients with COVID-19. Aims: To comparatively assess the plasma hemostasis parameters and results of the thrombodynamics test in patients with COVID-19 viral infection of different severity. Methods: The study included 96 patients with a confirmed diagnosis of COVID-19, admitted to a hospital for infectious diseases on the base of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology in the period from April 23, 2020, to June 20, 2020, and discharged at the end of treatment. SARS-CoV-2 was identified by PCR. The patients were stratified by the severity into 3 groups: mild course (n=25), moderate course (n=54), severe course (n=17). The diagnostics and treatment of patients were carried out in accordance with the Temporary Methodological Recommendations of the Ministry of Health of the Russian Federation for the prevention, diagnosis and treatment of the new coronavirus infection, versions 5, 6, 7. In the course of the treatment, the patients were assessed for APTT, prothrombin %, prothrombin time (PT) and thrombin time, fibrinogen, D-dimer, platelet count, and the thrombodynamic test parameters (V/Vi/Vst, Tlag, Cs, D). Results: Significant differences were observed in the thrombin time, D-dimer, platelet count, and the thrombodynamic parameters of V/Vst, Cs, and D taken before admission and a week after admission. We found a relationship between the parameters of hemostasis (fibrinogen concentration, PT, prothrombin %, APTT, Tlag, D) and the duration of hospital stay. There was a positive relationship between the content of fibrinogen and D (r=0.6307, p 0.0001) and a strong positive relationship between PT and Tlag (r=0.7499, p 0.0001). Conclusions: The thrombodynamics test can be recommended as a potential tool for a personalized approach to monitoring the hemostasis system and treating patients with COVID-19.

BACKGROUND: The prevalence of diabetes mellitus (DM) in pregnancy is on the rise. Despite that gestational hypercoagulability is a physiological condition, diabetic pregnancy is associated with a high risk of venous thromboembolic complications (VTEC). There are many surveys related to the hemostatic parameters in non-pregnant women, but studies in pregnant women are not enough.AIMS: To assess the coagulation and vascular-platelet hemostasis parameters in pregnant women with various types of diabetes mellitus, taking into account its correction method. The data were compared with these indicators in women with preeclampsia and healthy pregnant women at the same gestational age.MATERIALS AND METHODS: An observational, single-center, retrospective cohort study was carried out at D.O. Ott ­Research Institute of Obstetrics, Gynecology, and Reproductive Medicine. The study included 1994 pregnant women who presented several groups taking into account the type of DM and its correction method, a group of women with preeclampsia (PE), and healthy women. The analysis of clinical data was carried out at 28–32 gestational weeks from 2012 to 2017. The study’s primary endpoint was taken as indicators of fibrinogen content, prothrombin index, thrombin time, activated partial thromboplastin time (APTT), and international normalized ratio (INR) antithrombin III, D-dimer, von Willebrand factor, and fibronectin. Additionally, the incidence of VTEC during pregnancy and within six weeks after delivery, gestational arterial hypertension, preeclampsia, fetal growth restriction, premature birth, and stillbirth cases was assessed.RESULTS: in pregnant women with various types of diabetes mellitus and preeclampsia, a state of pathological hypercoagulation was observed compared to the control group. These changes were characterized by an increase and activation of the following blood parameters: fibrinogen, the degree and rate of platelet aggregation, D-dimer, homocysteine, von Willebrand factor, and fibronectin. At the same time, the content of antithrombin III was significantly reduced in patients with DM. Correlation analysis established a direct relationship between the range of the studied factors with the degree of glycemic control and the frequency of obstetric complications.CONCLUSIONS: Diabetes mellitus in pregnancy is associated with a hypercoagulation condition and overexpression in the synthesis of endothelial dysfunction markers. Moreover, the severity of these processes depends on the type of DM and the severity of metabolic disorders. In diabetic pregnancy, exceptional attention to coagulation indicators, regular monitoring, and preventive treatment is required in order to improve the perinatal outcomes.

The aim of the study was to determine experimentally the effect of hemodilution by the 2:1 sterofundin/gelofusine (SG) solution on hemostatic parameters in vitro and in vivo.Material and methods. Experiments were carried out on 75 male Wistar rats weighing 270–380 g and anesthetized with intramuscular tiletamine-zolazepam (40 mg/kg) + xylazine (10 mg/kg). Animals were divided randomly into 4 groups: Group 1 — in vitro 25-percent dilution of carotid blood samples by the SG solution (n=12), Group 2 — in vitro 37.5-percent dilution of similar samples (n=11), Group 3 — in vivo 25-percent dilution (n=10), Group 4 — the controls (n=42) with no dilution. The first stage of the study compared the in vitro dilution groups with the control group and with each other; the second stage compared the in vivo dilution group with the control group. The parameters of low-frequency piezoelectric tromboelastography (LFPTEG), clotting tests and complete blood count were studied to evaluate the effect of hemodilution.Results. At a 25-percent hemodilution with 2:1 CG solution in vitro and in vivo, the hemostatic parameters retained within the reference limits, but a trend to increased intensity of the enzymatic reactions of the coagulation cascade and a significant increase in clot polymerization in vitro due to relative anticoagulant deficiency became evident. In vitro 37.5-percent blood dilution significantly reduced the blood level of fibrinogen and platelet count, inhibited the intensity of the proteolytic stage of coagulation, reduced the clot density at the T3 gelation point, at 5 minutes after reaching it and the maximum amplitude (MA) of the LFPTEG curve, as well as significantly reduced anticoagulant activity of the blood. The observed changes in hemostatic parameters were significantly outside the reference limits, which may affect the interpretation of the experimental results and be clinically important. We found negative correlation between clot density and platelet activity at 25-percent dilution in vivo, whereas at 37.5-percent dilution in vitro an additional positive correlations between platelet count and fibrinogen levels were determined.Conclusion. A 25-percent hemodilution with 2:1 CG solution should be considered «safe» for the in vivo hemostatic system providing minimal effect on the in vitro parameters in the exper-iment.

Hemostasis is one of many well-known systems that ensure a constant conditions of the organism's internal environment. This process is usually divided into two main stages: coagulation and fibrinolysis. Both of them occur simultaneously and under physiological conditions they are in dynamic equilibrium. There are primary and secondary hemostasis. The primary hemostasis leads to the formation a platelet clot that forms almost directly after a blood vessel has been ruptured. In the other hand, the secondary hemostasis is the activation of coagulation, which leads to the strengthening of the platelet plug through the fibrin network formation as a result of the polymerization of the soluble plasma protein fibrinogen. The key role in hemostasis plays the interaction of platelets – which are the smallest non nucleated blood cells that are formed from the cytoplasm of megakaryocytes, and plasma coagulation factors with vascular endothelial cells and subendothelial tissues. In this report it is decribed the process of physiological hemostasis, especially the newer concept of blood coagulation.

Autoimmune diseases, including rheumatoid arthritis (RA), are risk factors for thrombotic events. Understanding the pathogenetic role of hemostatic changes in RA can assist in developing measures for prevention, prognosis, early diagnosis, and treatment of immune thromboses. Objective: to investigate the state of platelet and plasma hemostasis in patients with RA, as compared to other laboratory parameters and clinical manifestations of the disease. Subjects and methods. Hemostasis was investigated using two relatively new laboratory tests: thrombodynamics and kinetics of blood clot contraction (BCC). Examinations were made in 60 patients with RA and in 50 apparently healthy individuals of the control group. Results and discussion. In patients with RA, the parameters of thrombodynamics and BCC were found to be significantly different from the normal values. According to thrombodynamics, there was an increase in plasma clot growth rate, size, and density, which indicates chronic hypercoagulation. The rate and completeness of BCC were substantially reduced due to platelet dysfunction in patients with RA compared to healthy individuals. The changes in the parameters of thrombodynamics and BCC correlated with the laboratory signs of systemic inflammation and depended on the radiographic stage of the disease. Conclusion. The results of this investigation confirm that hemostatic disorders are present in RA and indicate the informative value of thrombodynamics and BCC tests as indicators of a pre-thrombotic state, including autoimmune pathology.

Tissue factor, being the main initiator of the blood coagulation in vivo, is involved in a number of physiological processes, such as angiogenesis or cell migration. These processes are not only significant for normal physiology, but also play a role in the development and progression of oncological diseases. This review presents data on the structure of tissue factor, its expression in normal conditions and in cancer, its role in thrombosis development associated with cancer, in angiogenesis and in metastasis. The involvement of tissue factor in such a wide range of physiological processes important for the progression of cancer makes it an attractive target molecule for therapy.

Urgency of the Problem. It is known that deep vein thrombosis of the lower extremities and pulmonary thromboembolism play an important role in the structure of postoperative morbidity and mortality, and these complications are characteristic of patients with different profiles. Considering the above, we consider it important to introduce into clinical practice new diagnostic methods that would be effective, reliable, and allow us to conduct research in real time. The Objective: to compare the methods for the instrumental study of blood coagulation properties and assess the capabilities of the method of low-frequency piezoelectric thromboelastography value in clinical practice. Materials and methods. Used various methods of instrumental studies of blood coagulation properties in the study of the functional state of the hemostatic system in a group of 60 healthy volunteers, as well as 74 patients with postthrombophlebitic syndrome. The ARP-01M Mednord APC indicators were correlated with data reproducible with the TEG® 5000 apparatus. To evaluate the reproducibility of the technique, a series of measurements of hemostasis parameters in healthy volunteers was performed. Conclusion. AIC ARP-01M Mednord is a compact, convenient and safe in operation coagulology analyzer that meets all the requirements of medical equipment. Due to these qualities, it can be successfully used not only in clinical laboratories, but also at the patient's bed, in the operating room, in an ambulance car.

In case of vessel wall damage or contact of blood plasma with a foreign surface, the chain of chemical reactions called coagulation cascade is launched that leading to the formation of a fibrin clot. A key enzyme of the coagulation cascade is thrombin, which catalyzes formation of fibrin from fibrinogen. The distribution of thrombin concentration in blood plasma determines spatio-temporal dynamics of clot formation. Contact pathway of blood coagulation triggers the production of thrombin in response to the contact with a negatively charged surface. If the concentration of thrombin generated at this stage is large enough, further production of thrombin takes place due to positive feedback loops of the coagulation cascade. As a result, thrombin propagates in plasma cleaving fibrinogen that results in the clot formation. The concentration profile and the speed of propagation of thrombin are constant and do not depend on the type of the initial activator. Such behavior of the coagulation system is well described by the traveling wave solutions in a system of "reaction - diffusion" equations on the concentration of blood factors involved in the coagulation cascade. In this study, we carried out detailed analysis of the mathematical model describing the main reaction of the intrinsic pathway of coagulation cascade.We formulate necessary and sufficient conditions of the existence of the traveling wave solutions. For the considered model the existence of such solutions is equivalent to the existence of the wave solutions in the simplified one-equation model describing the dynamics of thrombin concentration derived under the quasi-stationary approximation. Simplified model also allows us to obtain analytical estimate of the thrombin propagation rate in the considered model. The speed of the traveling wave for one equation is estimated using the narrow reaction zone method and piecewise linear approximation. The resulting formulas give a good approximation of the velocity of propagation of thrombin in the simplified, as well as in the original model.

Objective: To evaluate the relationship between the severity of post-stroke cognitive impairment (PSCI) and coagulation parameters assessed using the dynamic thrombophotometry., Material and Methods: Thirty-five patients with hemispheric ischemic stroke (IS) with moderate neurological deficit at admission were included. All patients underwent a comprehensive clinical and instrumental assessment according to the current guidelines. On days 10-14, the cognitive status of patients was assessed using the Montreal Cognitive Assessment (MoCA). Coagulation parameters were assessed using the dynamic thrombophotometry at admission, on 6-8 th days and 13-15 th days from the onset of the disease. A database of laboratory studies of 30 apparently healthy volunteers was used as a comparison group., Results: Data analysis revealed that a number of spatial and temporal parameters were within the reference values, and there were no significant changes over time. Nevertheless, though the optical density of the fibrin clot (D) was within the reference values, it showed a steady increase from the admission by the end of the 1 st week of the disease ( p =0.007) and by 13-15 th days ( p =0.009). Correlation and multivariate linear regression, including baseline stroke symptom severity, showed significant associations ( p <0.01 in all tests) between the higher optical density of the fibrin clot (D) on days 6-8 and 13-15 and lower MoCA score, confirming the negative effect of altered hemostatic parameters on cognitive function in IS patients., Conclusion: The increase of optical density of the fibrin clot (D) by 6-8 th and 13-15 th days is a potential prognostic biomarker for the early development of PSCI.

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Aim - to study the peculiarities of lipid and coagulation abnormalities in high risk patients, and also the possibilities of their correction with statin therapy. Methods. 102 patients were studied, 1 group included patients with LDL 3.0-3.9 mmol/l (n=59), who received atorvastatin 40 mg daily with titration to 80 mg daily, 2 group - patients with LDL >4.0 mmol/l (n=48), who received rosuvastatin 10 mg daily with titration to 20 mg daily. Results. In the 1 group of patients, after 24 weeks mean LDL level decreased by 43.3% (p

Obligatory detection of vWF blood levels, progesterone and testosterone levels in addition to routine tests are necessary to identify the causes of juvenile uterine bleeding. If progesterone level less than 1.75 ng/ml, and vWF activity in first phase of the cycle varies in the range 30–39 %, hyperpolymenorrhea may be due to coagulation disorders. Diagnostic range of vWF activity, within which hyperpolymenorrhea considered as a clinical sign of latent coagulation “disorders”, should be extended to 35 % for patients with O(I) blood group and to 39 % for patients with A (II), B (III) and AB (IV) blood group.

In this review we present a comparative analysis of alterations in hemostasis and blood coagulation during normal pregnancy with those in pregnant women with glycemic disorders (diabetes mellitus type 1 and 2, gestational diabetes).

The mechanisms of hydrodynamical activation of blood coagulation system are investigated in stenosed vessels for a wide range of Reynolds number values (from 10 up to 500). It is assumed that the vessel wall permeability for procoagulant factors rapidly increases when wall shear stress exceeds specific threshold value. A number of patterns of blood coagulation processes development are described. The influence of blood flow topology changes on activation of blood coagulation is explored. It is established that not only blood flow decrease, but also its increase may promote activation of blood coagulation. It was found that dependence of thrombogenic danger of stenosis on vessel lumen blockage ratio is non-monotonic. The relevance of obtained theoretical results for clinical practice is discussed.

Hemostatic disorders are frequent complication at patients with malignancy, resulting to decrease in efficiency of treatment, increase of its cost. Effective prevention and therapy are impossible without an adequate estimation of changes in coagulation system. Goal in writing this short review is to summarize the literature data about the hemostatic disorders in patient with prostate and bladder cancer.

Aim. To investigate hemostasis disorders caused by massive blood transfusions of artificial plasma replacing solutions (PRS). Material and methods. Two groups of patients were examined: 7 healthy volunteers without blood loss (group 1) and 11 healthy donors of bone marrow with intraoperative blood loss 1-2 l (group 2). Five patients of group 1 received transfusion of 12 ml/kg hydroxyethyl starch (HES) 130/0.4, two patients of group 1 received transfusion of modified gelatine solution (gelofusin). All of them received infusions (1-1.5 l) of crystalloid PRS (1-2 l) and infusion of one of colloid PRS (6-HES, 5 - gelofusin). Estimated hemodilution in group 1 was 1.17 ± 0.01 times, in group 2 it varied from 1.3 to 2.7 times (mean 1.78 ± 0.4 times). Hemostasis was studied by clot growth rate (for groups 1 and 2), endogenic thrombin potential and parameters of thromboelastography (for group 2) in plasm samples obtained before, 2.24 and 48 hours after infusion of colloid PRS. Results. For both groups spatial clot growth rate 2 hours after hemodilution was high. Then it fell and reached baseline level 48 hours after PRS infusion. Endogenic thrombin potential and thromboelastography data (for group 2) changed by the same pattern. A hypercoagulation effect of gelofusin on parameters of thromboelastography and clot growth rate was higher than of HES 130/04. Conclusion. Moderate hemodilution with PRS in vivo causes hypercoagulation which persisted longer than volemic effect of PRS.

The present research is focused on defining the role of protein С system in the process of blood coagulation and fibrinolysis in patients suffering from different forms ofperiodontitis. The beginning of specific course of treatment in patients with chronic periodontitis there have been diagnosed disturbances in protein С system, the latter being the reason for blood coagulation disorders, such as: the decrease of protein С activity, the decrease of active factor Va resistance, the increase ofplasminogen reserve, the decrease of total antithrombin blood activity, antithrombin III activity including. The degree of changes in protein С system depends on the severity degree of chronic periodontitis: the more severe disease is the more severe disorders itcauses in protein С system. The most evident symptoms of depression of indices in protein С system were observed in patients with quick-progressive periodontitis. The decrease of protein С activity is caused by its consumption in the process of intravascular blood coagulation is characteristic periodontitis.

Objective: To determine the features of preoperative hemostatic therapy and laboratory control in patients with severe and inhibitory forms of hemophilia A under preventive treatment by FVIII., Material and Methods: Four patients with severe and inhibitory forms of hemophilia A underwent surgery between 2021 and 2022. All patients received Emicizumab (the first monoclonal drug for «non-factor» therapy of hemophilia) for prevention of specific hemorrhagic signs of hemophilia., Results: Surgical intervention under preventive Emicizumab therapy was essential. Additional hemostatic therapy was not carried out or performed in reduced mode. There were no hemorrhagic, thrombotic or other complications. Thus, the so-called «non-factor» therapy is one of the variants for uncontrollable hemostasis in patients with severe and inhibitory forms of hemophilia., Conclusion: Preventive injection of Emicizumab ensures certain buffer of hemostasis system and stable lower limit of coagulation potential. This is the result of stable concentration of Emicizumab when used in any of the registered forms regardless of age and other individual characteristics. The risk of acute severe hemorrhage is excluded, while the probability of thrombosis is not increased. Indeed, FVIII has higher affinity than Emicizumab and displaces Emicizumab from coagulation cascade that does not result summation of total coagulation potential.

Objective: This work is to develop and use a new approach to the analysis of differences between the velocity profiles of registered light signals in groups of patients with schizophrenia and healthy donors., Material and Methods: The present study involved 62 patients (all female) with schizophrenia or schizoaffective disorders in the acute period (observational study - 2016-2017). 44 patients were diagnosed with paranoid schizophrenia with an attack-progredient type of course (F20.01 according to ICD-10) or with a continuous type of course (F20.02). The fibrinodynamics test (FD) was performed on the T-2 thrombodynamics device (Hemacore LLC, Moscow), which makes it possible to monitor the processes of coagulation and fibrinolysis in the cuvette channels filled with fresh blood plasma. The result of the test are the brightness profiles of the clot., Results: In the proposed approach, each profile is characterized by a vector of distances between it and other analyzed profiles. At that the distances between the profiles are calculated as the sum of the modules of differences at different points of the observation interval. This method makes it possible to overcome a certain loss of information that occurs when using a standard method based on the calculation of several parameters that characterize the analyzed velocity profiles. The method includes the construction of all kinds of statistically significant piecewise linear regression models that link the distances to two profiles. The velocity profiles corresponding to the points lying on opposite sides of the break point of such models have significantly different shapes. In practice, it turns out that for many piecewise linear regression models, the break points also significantly separate the velocity profiles for the compared groups of donors and patients with schizophrenia. Statistically significant deviations at the level p ≤0.01 exist for 16.1% of 3143 statistically significant piecewise linear models., Conclusion: The developed method makes it possible to visually establish the relationship between the shape of the velocity profile and the presence of the disease.

Membrane microparticles (MP) are released by activated or damaged cells and are able to accelerate blood clotting (coagulation). MP possess coagulation activity since all of them contain on their surface phosphatidylserine (PS), a substrate for the assembly of coagulation complexes, and some of them tissue factor (TF), the primary initiator of coagulation cascade reactions. We compared the coagulation activity and amount of MP in the blood of healthy donors (n=34) and patients with myocardial infarction (MI) (n=32), advanced atherosclerosis (AA) (n=32) and idiopathic pulmonary arterial hypertension (IPAH) (n=19). Total MP fraction was obtained from blood plasma by sedimentation at 20000 g, 30 min. The coagulation activity of PM isolated from 100 μl of donor and patient plasma was determined using a modified recalcification test. MP were added to substrate plasma devoid of endogenous MF, plasma was recalcified, and clotting was recorded by changes in optical density (A450), determining lag phase (min) and maximum rate (Vmax, %A450/min). MP were counted by flow cytometry as PS+ particles (lactadgerin-FITC staining) smaller than 1 μm and their concentration was expressed as 105 MP/μl plasma. MP in all patient groups accelerated plasma clotting more effectively than donor MP. Lag phase compared with donors (11.8 [11.0-13.1] median and interquartile range) was shorter in patients with AA (8.8 [7.0-10.3], p.

The aim of the work was a comparative study of Tocilizumab and Thymalin effects on the morphological composition and indicators of the blood clotting system in COVID-19 of middle aged and elderly patients. Severe COVID-19 patients were divided into 3 groups: 1st - control (basic therapy), 2nd - basic therapy +Tocilizumab, 3rd - basic therapy +Thymalin. Hospital mortality in COVID-19 patients after standard therapy, Tocilizumab and Thymalin application was 40,9; 28,4 and 20,6% accordingly. The number of platelets increased by 1,5 times, the concentration of fibrinogen in blood decreased by 78% and activated partial thromboplastin time decreased by 9,3% in patients taking Tocilizumab. Under the influence of Tocilizumab, the platelet/white blood cell and platelet/lymphocyte ratios increased by 1,6 and 1,4 times, which may be a predictor of an unfavorable outcome of COVID-19. Thymalin increased the number of lymphocytes and monocytes by 2 times, the number of leukocytes - by 1,3 times, the number of platelets in the blood - by 1,5 times. Thymain decreased the platelet/lymphocyte and neutrophil/lymphocyte ratios by 1,4 times and 2 times. The use of Thymalin decreased the level of fibrinogen, lactate dehydrogenase and D-dimer in the blood by 1,2; 1,8 and 1,7 times, respectively. Thymalin, compared with Tocilizumab, meets the principles of pathogenic therapy for severe COVID-19 of middle aged and elderly patients to a greater extent, having a normalizing effect on the morphological composition and indicators of the blood clotting system.

The authors demonstrate an importance of personalized approach to perioperative hemostatic therapy in a 48-year-old patient with hemophilia A and inhibitory antibodies. Laparoscopic hernia repair and extraction of 15 decayed teeth were performed. Hemostatic therapy included AICC and rFVIIa. Postoperative period was complicated by acute thrombosis of splenic artery and partial spleen infarction. An essential factor in splenic artery thrombosis was increase in blood coagulation potential under rFVIIa administration and depletion of fibrinolytic system (prolongation of XIIa-dependent fibrinolysis from 25 to 75 min) and antithrombin III decrease up to 81%. Cancellation of hemostatic therapy under TEG control ensured fast regression of arterial thrombosis and preservation of spleen. Individual characteristics of patients (compensatory mechanisms of coagulation, comorbidities, clinical changes) should be considered when prescribing hemostatic therapy in hemophilia patients. Perioperative control of all possible coagulation tests (routine and integral) is required for individual selection of hemostatic therapy and decrease of the risk of hemorrhagic and thrombotic complications.

Objective: To identify relationships between thrombodynamic values and the severity of the condition in patients with schizophrenia spectrum disorders (SSD) before and after treatment., Material and Methods: The study included 92 patients in an acute state of schizophrenia or schizotypal disorder, aged 16 to 57 years (median age [Q1; Q3] - 25 years). All patients received complex psychopharmacotherapy adequate to their psychopathological state. The PANSS was used to assess the severity of symptoms in patients. The coagulation parameters were determined by the thrombodynamics test, in which the growth of fibrin clots in platelet free plasma are observed from special activator. The patient population was divided into two groups with weak and strong response to treatment. Data analysis included machine learning (ML) techniques: logistic regression, random forests, decision trees, support vector machines with radial basis functions, statistically weighted syndromes, permutation method., Results: An analysis using permutation method revealed statistically significant different thrombodynamics values between groups of patients with weak and strong responses. There are significant differences between thrombodynamics values: T1D, T2D, T2Tlag and DTlag, and values characterizing the severity of positive symptoms before and after treatment (T1PposTot, T2PposTot), severity of psychopathological symptoms before treatment (T1Ppsy1, T1Ppsy6, T1Ppsy13). All ML techniques showed the relationship between thrombodynamics values and response to treatment. The best statistical significance was for statistically weighted syndromes method., Conclusion: The combination of the results of different ML techniques at a high level of statistical significance identifies the thrombodynamic predictors of weak effect of treatment of SSD.

Objective: To assess the possibility of using the integral indicators of thrombodynamics to improve the safety of rehabilitation measures in patients in the recovery period of stroke., Material and Methods: A prospective study included 52 patients in the recovery period of stroke. To compare the effect of the intensity of physical activity on the change in the integral indicators of thrombodynamics in accordance with the objectives of the study, the patients were randomized into two groups. In the first group, patients received treatment, including physiotherapy, stabilometric trainings, neuropsychological tasks. Patients of the second group received complex treatment, including more intense physical activity with the use of cyclic exercises, biomechanotherapy. To assess the state of hemostasis, an integral thrombodynamics test was used, and the numerical parameters of the spatial dynamics of the growth of a fibrin clot were calculated., Results: The state of compensated hypercoagulability was revealed in the majority of patients before the start of medical rehabilitation, despite taking antithrombotic therapy, which was evidence of the ineffectiveness of the therapy. At the same time, it was noted that it was its action, probably during the ongoing program of physical rehabilitation, that ensured the stability of the integral indicators of thrombodynamics and the absence of clinically significant unwanted thromboembolic complications. As a result of the analysis of the data in dynamics before and after treatment, a direct relationship was traced between the intensity of physical activity and the tendency to disturb the hemostatic balance., Conclusion: The intensity of physical activity during treatment undoubtedly influenced the state of hemostasis. The expediency of monitoring the dynamics of coagulation activity in patients in the recovery period of stroke has been demonstrated.

Congenital coagulation disorders account about 1-2% and can pose a serious risk for neurosurgical patients. Indeed, coagulation management in these patients is essential to ensure normal hemostasis. Analysis of available literature devoted to this issue and case series of neurosurgical patients with congenital coagulation disorders. Literature data were obtained from the PubMed, Cochrane Library, Medline and Google Scholar databases for the period from 2019 to 2020. Over 200 reports devoted to our scientific issue were selected. We determined the key features of perioperative management of neurosurgical patients with congenital coagulation disorders. We have also analyzed 10 similar patients for the period from 2008 to 2020. Comprehensive analysis of anamnesis, adequate diagnosis, perioperative planning and multidisciplinary approach are essential for successful elective surgery in patients with congenital coagulation disorders.

The aim of this work was to study the reaction of coagulation hemostasis in response to hypoxia in rats young and mature, exposed to hypoxia in the embryonic, prefetal and fetal stages of prenatal ontogenesis. With the help of some hematological tests, a comparative analysis of blood coagulation indices was performed, both of males and females of experimental and control rats. To assess the general condition of the blood coagulation system, the time of clot formation, the time of plasma recalcification, and the concentration of fibrinogen were determined to assess the final stage. A comparative analysis of the data showed that intrauterine hypoxia of the fetus causes a significant change in blood coagulation. The opposite effect of prenatal hypoxia depending on the degree of development was revealed. So, in one-month-old rats, a hypocoagulation shift was established. Since weakened blood coagulability was detected in experimental animals. And in six-month-old experimental rats, a hypercoagulable shift in the system was observed, an increase in blood coagulation was recorded compared with control animals. The degree of severity of the changes occurring in the body during hypoxia (regardless of the cause), determined by the duration, intensity of oxygen deficiency, and in what period of embryonic development the same as its effect. It turned out that the embryonic period of fetal development is more susceptible to the effects of hypoxia. It is assumed that prenatal hypoxia forms a new ratio of hemocoagulation factors. We can say that the level of these shifts was determined by the severity of hypoxia, and the observed changes were associated not with an increase or decrease in the concentration of one coagulation factor, but with a shift in the dynamic equilibrium of the entire system.

Objective: To identify a possible correlation between parameters of thrombodynamic coagulation and negative syndromes in patients with schizophrenia., Material and Methods: The study included 148 female inpatients, aged 16 to 57 years, with the following mental disorders: schizophrenia with attack-like/attack-progressive/continuous type of course (F20.00-2), schizotypal disorder with affective fluctuations (F21.3-4). The thrombodynamics test (TD) was carried out on a T-2 thrombodynamics recorder (Hemacore LLC, Moscow, Russia)., Results: A positive correlation was shown between the thrombodynamic parameters of clot growth rates (V, Vst, and Vi), clot size at the 30th minute (CS), and the total severity of negative syndromes (PANSS). There is a negative correlation between the time of spontaneous clots (Tsp) and the total severity of negative syndromes in patients. Positive correlations of V and Vst with scores on the fourth (Passive/apathetic social withdrawal), fifth (Difficulty in abstract thinking) and seventh (Stereotyped thinking) items of the PANSS negative subscale were revealed. There is a negative correlation between Tsp and the score on the 7th item, i.e. a shorter time for the appearance of spontaneous clots corresponds to a more pronounced Stereotyped thinking in patients., Conclusion: For the first time, correlations between thrombodynamic indicators of hypercoagulation and negative syndromes in patients with schizophrenia are identified, which emphasizes the need to normalize hemostasis to prevent further aggravation of these disorders.

The thematic review presents modern solutions using oral anticoagulants with a focus on direct coagulation factor X inhibitors. It contains information about the pharmacodynamics and pharmacokinetics of apixaban and rivaroxaban against the background of different drug intake regimens - twice and once per day. There are shown studies of concentration dynamics and the corresponding functional response, measured using the integral method - the thrombin generation test, which is widely used in scientific research to describe hemostatic processes based on an objective quantitative assessment of the thrombin formation - a key coagulation cascade serine protease. The logical relationship between the pharmacodynamics of anticoagulant action and the clinical presentation of the effectiveness and safety of drugs is traced. The review provides links to actual literature and current clinical guidelines.

In the conclusion of the council of experts (list of participants see text) the following issues are discussed: regional specifics of diagnostics and therapy of patients with ischemic heart disease (IHD) and / or peripheral arterial disease (PAD), methods of risk assessment in patients with stable course of atherosclerotic disease, pathogenetic validity of simultaneous inhibition of coagulation and platelet thrombus formation, as well as clinical significance of a novel therapeutic approach - combined use of rivaroxaban and acetylsalicylic acid (ASA). Possible problems and ways to their solution at implementation in clinical practice of the novel scheme of antithrombotic therapy are presented. Importance of multidisciplinary approach to management of patients with IHD and concomitant diseases is stressed. Experts have noted that after registration of the corresponding indication therapy with rivaroxaban 2.5 mg twice daily and ASA 75-100 mg once daily might be recommended to majority of patients with atherosclerotic involvement of blood vessels. In real clinical practice prescription of this therapy is appropriate first of all in patients with IHD and high risk of complications - with multifocal atherosclerosis, with history of myocardial infarction after stoppage of dual antiplatelet therapy, - patients with concomitant diabetes, heart failure, and other prognosis worsening comorbid diseases. Experts express hope that in the nearest time combined antithrombotic therapy will be included into corresponding national clinical recommendations.

Membrane microparticles (MP) produced upon cell activation and/or damage possess coagulation activity, i.e. ability to accelerate blood clotting. They contain on their surface phosphatidylserine (PS), a substrate for assembling coagulation enzymatic complexes, and some of them tissue factor (TF), the initiator of clotting cascade reactions. In this study coagulation properties of MP derived from erythrocytes have been investigated. These MP were obtained from donor's erythrocytes activated with ionophore A23187 as well as from outdated erythrocyte concentrates for transfusion. MP were counted by flow cytometry. Coagulation activity of MP was examined by modified plasma recalcification assay. Involvement of PS and TF in this reaction was assessed using PS blocker lactadherin and anti-TF antibodies. TF activity in MP was measured by its ability to activate factor X in a chromogenic assay. Size of MP was evaluated by dynamic light scattering. Properties of erythrocyte MP were compared with previously characterized (using the same methodological approaches) MP derived from platelets and monocytic THP-1 cells, lacking and containing TF, respectively. Erythrocyte MP accelerated plasma clotting, but less actively than MP from platelets and MP from THP-1 cells, which demonstrated maximal activity. Lactadherin completely inhibited coagulation activity of all MP. Anti-TF antibodies did not affect clotting parameters in the presence of platelet and erythrocyte MP, but slowed clotting in the presence of MP from THP-1 cells. TF activity was not detected in erythrocyte and platelet MP, unlike MP from THP-1 cells expressing active TF. MP derived from erythrocytes were smaller than MP from platelets and THP-1 cells, with average diameter about 200 nm and 400 nm respectively. Thus, MP from erythrocyte possess less ability to accelerate plasma clotting in comparison with MP from platelet and THP-1 cells. The data obtained suggest that lesser coagulation activity of erythrocyte MP in comparison with MP from THP-1 cells is due to the absence of TF in erythrocyte MP (in contrast to MP from THP-1 cells) and to their smaller size, and in comparison with MP from platelets (which as erythrocyte MP do not express TF) is due to their smaller size only.

The maintenance of normal blood flow through the vessels is the result of the coordinated work of the coagulation and anticoagulation systems of our body. The balance of this system depends on many factors, including endothelial, humoral, platelet ones, however, we still lack knowledge about the effect of antigenic determinants on the state of the hemostatic system. This study is devoted to assessing the effect of the presence and absence of antigens on the AB0 system, presented on erythrocyte and platelet membranes, on hemostatic parameters. The study was conducted in the Clinics of Samara State Medical University and consisted of127 clinically healthy individuals who underwent a general analysis and biochemical blood analysis, 52 people with the most stable indicators of cell composition and metabolic profile were selected for a coagulation test, including determination of the activity of coagulation factors and routine tests. A significant decrease in the activity of the VIII and VII coagulation factors was revealed, as well as an increase in the prothrombin time in patients with 0 (I) blood group compared to the "antigenic" blood groups. The presence of biological variation for indicators of external and internal coagulation paths was noted, depending on the group of blood belonging to the AB0 system. The findings suggest that there is an increased susceptibility to bleeding in patients with 0 (I) blood groups due to the absence of antigenic determinants on the cell membrane, while for "antigenic" blood groups, on the contrary, there is a susceptibility to thrombosis due to increased activity of the components of the coagulation system., Competing Interests: The authors declare no conflict of interest.

Aim: To detect coagulability impairment of blood plasma in patients with schizophrenia or affective disease in a state of exacerbation using a thrombodynamics test., Material and Methods: The study included 46 women, 32 with attack-like/shift-like/or continuous schizophrenia (ICD-10: F20.00, F20.01, F20.02), 7 with schizotypal disorder (ICD-10: F21.3-21.4) and 7 with affective disorder (ICD-10: F32.00, F32.3). Thrombodynamics tests were performed on T-2 thrombodynamics analyzer ('Hemacore LLC', Moscow, Russia)., Results: For the first time, it was shown that in the patient population (n=46), the thrombodynamic parameters of the blood clot growth rate [initial velocity (Vi), steady-state velocity (Vst) and spontaneous clots adjusted velocity (V)] and clot size at 30 minute of thrombodynamics (Clot Size, CS) were significantly higher than normal values. The mean appearance of spontaneous clots (Tsp) was significantly lower than 30 minutes (p<0.0001) which indicated a rapid, spontaneous clots formation. The mean value of clot lag time (Tlag) and clot density (Density, D) did not differ significantly from normal values. The number of changed thrombodynamic parameters decreased in the following sequence: schizophrenia with different types of courses > schizotypal disorder>affective disorder. This is in good agreement with the fact that the course of affective disorders is more favorable than that in schizophrenia., Conclusion: The thrombodynamics test has a good potential for introduction into medicine to detect hypercoagulability and increased risks of thrombotic complications in patients, as well as to control for normalization of hemostasis with antiaggregant or anticoagulant drugs. Thrombodynamics makes it possible to identify a tendency to hypercoagulable states at an early stage, when other methods are still not sensitive enough. The study identified the hypercoagulability in patients with schizophrenia and affective disorders.

The most failures in the process of laboratory analysis occur at the pre-analytical stage. The percentage of samples of blood serum with hemolysis and percentage of samples of EDTA of whole blood with clots are largely applied as indices of quality of venous blood sampling. The analysis of data from 28 laboratories established no relationship between percentage ofsamples with hemolysis and percentage of samples with clots. Prior to implementation of more large-scaled studies, the level less than 1% of samples with hemolysis can be accepted as a minimal level of quality of blood sampling and the level less than 0.4% of samples of total blood with clots can be accepted as a minimal level of quality ofpreparation of samples after blood drawing from vein for analysis using hematological analyzers. both indices can be applied for estimating efficiency of measures concerning amelioration of quality of procedure of blood drawing from vein. By all appearances, the ideal sample for control of quality of blood drawing in the nearest future can become sample of blood drew from vein into vial with citrate for analysis using modern coagulometric analyzer. This sample can become a source for calculation of several indices of quality of venous blood drawing (hemolysis, clots, vial filling and violation of ration sample-anticoagulant).

The purpose of the research was to study the lipid profile, some indices of hemostasis and cytokine status of rosacea patients with severe climacteric syndrome. Serum lipid profile was studied by means of the following parameters: total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (the study of lipid profile was performed by the device "INTEGRAM +400" (Company "ROSH»). Haemostatic system was evaluated in terms of prothrombin, thrombin time. Content of fibrinogen, fibrinolytic activity, and prothrombin index were determined. The concentration of free VEGF (vascular endothelial growth factor) and IL-8 were measured by ELISA. The results of these studies suggest that the phenomenon of hyper coagulation and disorders in lipid profile of blood serum in patients with rosacea with climacteric syndrome can be considered as risk factors of cardiovascular disease. From the other side, as a powerful provocateur of increased permeability, atony and fragility of vessel walls, VEGF, IL-2, IL-8 may be directly related to the mechanism of the development of cardiovascular disease in rosacea patients.

The analysis of the influence of the intra-abdominal hypertension on the blood coagulation system by carrying out an experimental research with laboratory animals is presented in article. After simulating intra-abdominal hypertension with different degree and exposition we made the laboratory research of blood coagulation system (fibrinogen, PTI, SFMC, APTT) and ELISA research on the concentration of the modern marker of thrombozis - D-dimer. The results in article clearly demonstrate that there is a direct linear dependence of level of fibrinogen and SFMC on degree of intra-abdominal hypertension, and the multidirectional changes of indicators with increase of intra-abdominal hypertension duration - towards hypercoagulation for 3-12 hours, and then by 24 o'clock - in the opposite direction towards hypocoagulation. Perhaps, it is explained with development of organ dysfunction and a coagulopathy of consumption. Indicator D-dimer has also direct linear dependence on the intra-abdominal hypertension level with contents peak at 3 hour exposition, and at all intra-abdominal hypertension levels, more than 2-fold rise of D-dimer level is statistically significant.

Direct effects of circulating blood microparticles on fibrin formation and structure were studied. Clots made from platelet-free plasma and from microparticle-depleted plasma obtained by filtration was studied in parallel, including clots from the microparticle-depleted plasma replenished with phospholipids. Fibrin formation was induced by exogenous thrombin without Ca2+ to prevent formation of endogenous thrombin and exclude indirect kinetic effects of microparticles related to thrombin generation. In the presence of natural microparticles or exogenous phospholipids the maximal turbidity of fibrin clots was significantly smaller, indicating structural distinctions from the clots formed in the absence of microparticles. Scanning electron microscopy and confocal microscopy showed that clots formed from platelet-free plasma, i. e. in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contained 0.1-0.5-μm-large CD61-positive granules associated with fibrin fibers that were identical to the particles found on the surface of filters used for microparticle removal. The results show that platelet-derived microparticles bind to fibrin and affect its structure. The revealed interactions of cell-derived microparticles with fibrin highlight a previously unknown role of microparticles in hemostasis and thrombosis as constituents and modulators of a fibrin clot structure.

Aim: to investigate parameters of fibrinolysis in patients on long-term warfarin (W) therapy, and assess their relation to the risk of recurrent bleeding occurring at therapeutic international normalized ratio (INR)., Materials and Methods: Our prospective study involved 78 W-naive patients (40 men, age 64.3+/-12.2 years). Follow up period was 5.6+/-3.4 months. INR was measured monthly; determination of coagulation parameters (D-dimer, fibrinogen, complex plasmin-2-antiplasmin [PAP] and thrombin-activatable fibrinolysis inhibitor [TAFI] was performed before and after at least 3 months of W therapy., Results: During follow-up bleedings occurred in 47 (60.3%) patients, 26 patients (33.3%) had recurrent bleedings at therapeutic INR and 21 patients (26.9%) had single bleeding. Mean time in therapeutic range (TTR) was >70.

The study was carried out to diferentiate reference values for kaolin-activated thromboelastography in newborns with congenital heart disease. The study included two groups ofpatients. The first one consisted of 62 newborns with congenital heart disease and the second one consisted of 35 healthy newborns. The results of kaolin-activated thromboelastography implemented in groups are evaluated as condition of normal coagulation. The valuable diferences of homeostasis system in healthy newborns and newborns with congenital heart disease (without severe concomitant pathology) are not established. They have similar indicators of kaolin-activated thromboelastography. The derived results can be applied as standards in full-term newborns with congenital heart disease.

All major coagulation reactions do not occurs in blood plasma itself, these processes are actually two-dimensional reactions localized to thephospholipid membranes. Almost all blood cells, lipoproteins, and microparticles provide assembly of protein complexes. A central role among them are played by platelets and platelet-derived microparticles. On their membranes occurs the most important coagulation reactions such as activation of prothrombin by prothrombin complex, activation of factor X by complexes intrinsic and extrinsic tenase. This reactions are important for processes activation of the contact path coagulation, activation factor XI by thrombin, appearance of enzymatic activity of factor VIIa etc. This review is focused on the membrane-dependent reactions, here are discussed mechanisms and regulation these reactions and the possible prospects of the study.

The effects of blood microparticles (MPs) on the dynamics of fibrin polymerization, clot structure and susceptibility to fibrinolysis were studied. Kinetics of fibrin polymerization, fibrinolysis, thrombin generation in platelet-free, microparticle-depleted and microparticle-depleted plasma replenished with cephalin, from healthy donors were analyzed in parallel. MPs have profound effects on all stages of fibrin formation, decrease its turbidity. All parameters obtained in the absence of MPs were recovered after reconstitution of phospholipids. Thrombin generation rates were reduced in the absence of MPs. In the presence of MPs the fibrin networks had less poro us structures with thinner fibers, while clots formed in the absence of MPs had larger pores and were built of thicker fibers. Clots formed in the presence of MPs were significantly more resistant to fibrinolysis. Results show that normally circulating MPs can support the formation of stable clots at the sites of vascular injury.

Background: Heavy bleeding is developed in case of spleen injury. It often leads to death. At present the search and development of new methods for hemostasis of spleen bleeding continues. An innovative method is coagulation of nonequilibrium plasma., Objective: Our aim was to study the effect of nonequilibrium plasma on the morphofunctional state of the spleen., Methods: The non-randomized study by type of "case-control" was conducted. The experiment was carried out on 45 male rabbits weighing 3000-3200 g. 1st group (control; n = 5)--intact animals without surgery; 2nd group (experimental, n = 40)--animals after atypical resection of the spleen and hemostasis by nonequilibrium plasma. The volume of blood loss, FBC, histological data, splenogram analysis data were assessed at defined periods (60 min, 3rd, 5th, 7th, 14th, 30th, 90th, 180th days) after surgery. They were compared with data of the control group., Results: The volume of blood loss during the resection of the spleen with hemostasis by nonequilibrium plasma was 16.6 [15.98; 17.22] ml. Increase of neutrophil to 38 [24; 39] (control group 17[13, 18], p = 0.009), monocytes to 15 [14, 18] (control group 8 [6, 11], p = 0.036) is revealed in the FBC in the early period after hemostasis with nonequilibrium plasma. It is reduced to the norm on 30 day. Histological examination revealed leukocyte infiltration, edema, microvascular stasis, dilatation of vessels in the early period. At long-term period structure of the organ is normalized. Splenogramm analysis revealed a statistically significant (p = 0.023) decrease in the relative number of small lymphocytes by 28% in animals after hemostasis with nonequilibrium plasma as compared to control (23.3 [179; 26.7] versus 30.8 [29.25; 34.3] respectively)., Conclusion: treatment of bleeding surface by plasma flow for 1.5-2 min is required order to achieve effective hemostasis during surgery of spleen injuries in the experiment. After coagulation there is minimal damage of the spleen parenchyma, which manifests itself as activation reaction. At long-term period parenchyma ofthe spleen completely regenerates with theformation of cicatrical tissue that does not affect thefunctioning of organ.

Objective: To improve treatment results of women with massive obstetrical blood loss. Subjects and methods: 96 female patients with average and heavy degree preeclampsia worsened massive blood developing were involved into the investigation. The women were divided into two groups: main (n=55) (basic) - it's patients were treated with complex of offered wiays control (n=41) - it's patients were evaluated retrospectively. During the investigation the parameters of hemostasis system and periphery blood values were performed as dynamic evaluations, acidity-basic state and water-electrolyte balance parameters, medical history were monitored., Results: As a result of the investigation it was found out that these offered actions complex application about reducing massive obstetric blood accelerates restoration of clinic, bio-chemical paramnleters during the early post-operating period, Conclusion: The application of the offered methods has reduced both inltraoperative blood loss in women with preeclamsia and use of blood components and the time spent on the hemostasis system correction for all the women of the base group.