Hemostasis System Research Articles

Status of coagulation system in adolescent rats exposed to hypoxia during prenatal development

The goal of the research was to investigate the physiological indicators in the hemostasis of adult offspring developed under prenatal hypoxia conditions. Chronic hypoxia conditions were created during different periods of the pregnancy. Three-month-old white rats that had completed the period of puberty were used in the experiments. Clinical analyses of the main indicators of the coagulation system were performed to assess the state of the hemostasis system. The effect of intrauterine hypoxia on the "mother-fetus" relationship was manifested by prolonged pathological changes in the blood coagulation and expressed changes in the liver parenchyma at the later stages of development.

RELATIONSHIP BETWEEN HAEMOSTATIC AND MACRO-MICROHEMODYNAMIC PARAMETERS IN RATS UNDER EXPERIMENTAL EXPOSURE TO CADMIUM. MEANS OF PREVENTION

In experiments on Wistar rats, it was shown that the prophylactic administration of melatonin at a dose of 5 mg/kg helps to reduce the manifestations of toxic coagulopathy, preventing the development of micro- and macrohemodynamic disorders in rats with chronic cadmium intoxication. Correlations between changes in indicators of the hemostasis system with the restoration of linear and volumetric blood flow rates and a decrease in the Pourcelot peripheral resistive index were revealed. These effects correlated with a decrease in the level of lipid peroxidation products and the activity of antioxidant enzymes in the blood under the influence of melatonin. The results of the experiments suggest further studies on using melatonin for the prevention and correction of the procoagulative and pathocirculatory effects of cadmium.

The influence of prolonged high-adsorption membrane hemofiltration on the hemostatic system in patients with COVID-19

The objective was to evaluate the effects of prolonged (24–72 h) high-adsorption membrane hemofiltration on the hemostatic system.Materials and methods. A retrospective study included 91 patients with COVID-19 who received prolonged high-adsorption membrane hemofiltration (Prismaflex system) as part of complex therapy. The group was divided into two subgroups, taking into account the outcome of the disease. We analyzed the level of D-dimer, fibrinogen, platelet count, percentage of large platelets, thromboelastogram indicators, reflecting external and internal coagulation pathways (Intem, Extem) before and after the procedure. The levels of serine proteases (tPA, PAI) were additionally analyzed in 35 cases.Results. An increase in the D-dimer level, accompanied by a decrease in the fibrinogen concentration, was detected after sorption, which was especially noticeable in patients with unfavorable outcome (by 2.8 times). The thromboelastogram parameters after the procedure did not go beyond the normal range, the level of tPA and PAI became lower in both subgroups but there was no connection with the outcome.Conclusion. Prolonged high-adsorption membrane hemofiltration in COVID-19 patients does not have a negative influence on hemostasis system. A decrease in fibrinogen level after the procedure is associated with its mechanical removal from the circulation because of fibrin adhesion on the filter’s membrane and on sets’ walls; an increase in the D-dimer level should not be associated with the detection of degradation of fibrin networks.

Changes in the hemocoagulation system in pregnant women, after pre-gravid preparation before the DRT program, with a history of sexually transmitted infections

The objective: to analyze the dynamics of laboratory parameters of the functioning of the thermocoagulation system in pregnant women with a history of sexually transmitted infections(STIs) after pre-gravid preparation before cycles of assisted reproductive technologies (ART). Materials and methods. An analysis of the functioning of the thermocoagulation system was carried out in women with infertility who had a history of STIs after the DRT program: GroupI – 56 pregnant women received our proposed treatment and prevention measures in the pregravidperiod; II group – 55 pregnant women received generally accepted medical and preventive measures. The assessment of the state of the hemostasis system was determined by the following indicators: fibrinogen concentration (Fg), activated recalcification time (ACR), activated partial thromboplastin time (ATP), integrative indicator «Thrombodynamic Potential Index» (TIP), the concentration of fibrin and fibrinogen degradation products (FRP). and the level of more stable, but less biologically active metabolites of prostacyclin and thromboxane – 6-keto-PGF1α and T×B2. Statistical processing of research results was carried out using standard programs «MicrosoftExcel 5.0» and «Statistica 8.0». Results. In the period of the final formation of the placental barrier, in pregnant women of the Igroup, the APTC slowly lengthened (31.3±1.6 s in the II trimester, 34.3±2.9 s in the III trimester)with an increase in gestational age and probably differed from the indicators in the II group(27.6±3.0 s and 30.2±1.7 s respectively; p<0.05); there was a slow reduction of AChR during the II and III trimesters of pregnancy in pregnant women of the I group (63.1±2.8 s, 59.3±2.8 s); gradual decrease in the level of PDFF (5.8±0.27×10-2 g/l, 5.1±0.22×10-2 g/l) in contrast to the level of PDFF in the II group, where a gradual increase of this indicator was observed (9.4 ±0.17×10-2 g/l, 11.6±0.27×10-2 g/l) (р<0.01). The level of a stable metabolite of thromboxane (T×B2) in the trimesters decreased by 2 times and was found to be lower (p<0.05) than in the II study group; the level of a stable metabolite of prostacyclin (6-keto-PGF1α) also increased in the III trimester(p<0.05). This led to an increase in the PgI2/T×A2 balance in group I from 0.34±0.02 to 1.16±0.03, which corresponded to the physiological needs of systemic and organ hemodynamics during pregnancy. Conclusions. The development and implementation of effective pre-gravid preparation before cycles in women with a history of STIs and medication correction during pregnancy contribute to increasing the adaptive compensatory and adaptive potential of the mother’shemocoagulation homeostasis and perinatal protection of the fetus.

INFLAMMATION AS A FUNDAMENTAL PATHOLOGICAL PROCESS: LECTURE 1 (ALTERATION, VASCULAR REACTIONS)

Inflammation is the most widespread pathological process in medical practice. Inflammation is the basis of the vast majority of diseases. In this connection, the topic is actual for any medical student, as well as a doctor of any specialty. Local signs of inflammation (redness, swelling, heat, pain, dysfunction) were described more than two thousand years ago. Like any typical pathological process, inflammation includes protective and damaging reactions. Their knowledge is very important for understanding the pathogenesis of inflammatory diseases. The first part of the lecture describes the causes and mechanisms leading to the development of inflammation, as well as the consequences of tissue damage (acidosis, hyperonkia, hyperosmia, synthesis and release of inflammatory mediators). Inflammatory mediators are biologically active substances those regulate all reactions in the focus of inflammation. Various cells (neutrophils, macrophages, lymphocytes, endothelial cells, hepatocytes, etc.) can be sources of mediators. By origin, mediators are divided into cell-derived (biogenic amines, derivatives of arachidonic acid, lysosomal enzymes and reactive oxygen species, cytokines) and plasma-derived (components of the complement system, kinins and the hemostasis system). There are pro-inflammatory mediators (they increase inflammatory response) and anti-inflammatory ones. Under the influence of inflammatory mediators, changes in microcirculatory blood flow begin (vasospasm, arterial hyperemia, venous congestion, stasis) and exudation develops. Exudation is caused by an increase in the permeability of microvessels, its mechanisms are different. The composition of the exudate is determined by the cause of the inflammation and degree of tissue damage, the spectrum and amount of chemoattractants influence the type of exudate as well. The main types of exudates are serous, purulent, fibrinous, hemorrhagic, ichorous, catarrhal.

Spontaneous soft tissue hematomas in patients with severe COVID‑19 infection

Relevance. Spontaneous hematomas (SG) appear after 2–3 weeks from the start of treatment for COVID infection and are observed mainly in elderly people with concomitant pathology. The predisposing factors for the development of SG in patients with COVID-19 are coagulopathies. The mortality rate in SG is 04–30 %, while in patients with COVID infection in severe cases increases to 30–50 %. The purpose of the study. To determine the role of coagulological changes in the development of soft tissue SG and to identify the features of the course, taking into account localization in patients with COVID infection. Materials and methods. The results of diagnosis and treatment of 54 patients with spontaneous hematomas were analyzed. The average age was 68.5 years (38–93), there were 45 women (83.3 %), 9 men (16.7 %). Lung damage by CT in most patients was severe. Anticoagulant and antiplatelet therapy was prescribed to all patients from the moment of admission. The management tactics of patients was carried out on the basis of a comprehensive instrumental assessment. Results. SG was mainly observed in retroperitoneal tissue (28) of patients, chest wall (14), rectus abdominis muscle (6), combination of hematoma of preperitoneal and retroperitoneal tissue (3), other localization of neck, hip, mediastinum (3). The volume of SG ranged from 60 to 2850 cm 3 . Unfractionated heparin was used as anticoagulant therapy. All patients had a statistically significant decrease in the level of hemoglobin and erythrocytes relative to the norm during all study periods (p < 0.05). The number of platelets decreased statistically significantly in the group with SG with localization in retroperitoneal tissue and in the chest (p < 0.05). The level of PH at admission was reduced in patients with SG with localization in retroperitoneal tissue and in the chest relative to the norm (p<0.05). The value of D-dimer was statistically significantly increased relative to the norm during all study periods in all groups. The treatment was aimed at correcting hemostasis, hemotransfusion with a decrease in hemoglobin levels below 60 g/l, plasma transfusion and thromboconcentrate. Conclusions. The severity of patients with SSG of various localization is due not only to the volume of SG against the background of COVID infection, but also to a variety of concomitant diseases, features of localization, volume and nature of SG. In patients who initially have deviations in the indicators of the hemostasis system, the risk of OHSS is higher, they need to more carefully select the optimal doses and the course of thromboprophylaxis. Early diagnosis using ultrasound, CT, X-ray endovascular hemostasis against the background of hemostatic therapy contributes to the stabilization of the condition and a favorable outcome.

Studying the Range of Proteolytic Activity of New Strains of Aspergillus Micromycetes in Relation to Proteins of a Hemostasis System

Studying the Range of Proteolytic Activity of New Strains of Aspergillus Micromycetes in Relation to Proteins of a Hemostasis System

Особенности ведения периоперационного периода у пациентов с хроническим гепатитом и циррозом печени при выполнении офтальмохирургических операций

Purpose. Study of frequency and structure of hepatitis and cirrhosis among ophthalmic surgical patients. Material and methods. Among 1706 patients, 43 patients with chronic hepatitis and cirrhosis were selected. A clinical assessment of their etiology, severity, and possibility of performing ophthalmic surgery in these patients was carried out. Results. The average age of the selected 43 patients was 64.1 ± 9.7 years, in 72.1 % they conasist in elderly age group. 88.4 % had viral hepatitis (B, C, chronic HBV and HCV coinfection), 9.3 % had a toxic hepatitis, and one patient (2.3 %) had autoimmune hepatitis. Among hepatitis, HCV monoinfection prevailed (55.4 %). The vast majority (97.7 %) had minimal disease activity. Although violations of hemostasis system were detected in 9 patients, signs of significant hypocoagulability were observed in 3 people (6.9 %). After 3-days course of intramuscular injections of vitamin K 2–3 times a day, all 3 patients underwent successful ophthalmic surgery. 97.7 % of patients were admitted to surgery: 39 people. – in planned manner, 3 people – after medical preparation. In one patient with suspected acute viral hepatitis B, planned surgical treatment was postponed. Conclusion. In general structure of ophthalmic surgical patients, the proportion of patients with hepatitis and cirrhosis was 2.5 %. Viral hepatitis B and C prevailed (88.4 %), HCV monoinfection dominated (55.4 %). The vast majority of patients (97.7 %) had minimal hepatitis activity, 6.9 % had signs of significant hypocoagulability, which required their preoperative preparation. Keywords: hepatitis, cirrhosis, ophthalmic surgery

The Relationship of Disorders in the Hemostasis System with Changes in Homeostasis in Conditions of Progressive Inflammation

The urgency of the problem of acute peritonitis in surgical practice is due to the annual increase in morbidity, a high number of complications, therapeutic complexity and mortality. Materials and methods. The material of the study was 45 patients with acute peritonitis, who were divided into 3 groups depending on the course of pathology after surgery. The first group (n=15) – without complications, the second (n=15) – with wound complications, the third (n=15) – with tertiary peritonitis and sepsis. In addition to standard research methods, a number of laboratory tests are included to determine the severity of intoxication, oxidative activity, the state of the blood coagulation system, and the functional state of the liver. The study period is the 1st, 5th, 10th postoperative day. Results. The results showed that in the early period after surgery in patients with acute peritonitis, the state of hypercoagulemia, inhibition of fibrinolysis correlate with lipid peroxidation, endogenous intoxication, and violation of the functional status of the liver. With effective therapy, during the early postoperative period, the state of the hemostasis system and homeostasis indicators are corrected against the background of restoration of the functional status of the liver. With the aggravation of the phenomena of inflammation in the early postoperative period and the development of complications, there is a progression of changes in the studied indicators of homeostasis and hemostasis with further inhibition of the functional state of the liver. With the development of tertiary peritonitis and sepsis, the hemostasis system is modified in the form of hypocoagulemia and activation of fibrinolysis against the background of a sharp increase in endogenous intoxication, lipid peroxidation and greater inhibition of the functional status of the liver, including from its hemostasis-regulating component. Conclusions. The obtained results indicate the presence of a reliable correlation of disorders in the hemostasis system with changes in homeostasis in conditions of progressive inflammation.

Experimental study of morphological changes in the heart and blood vessels in the course of chronic fluoride intoxication

Introduction. Clinical studies have shown the development of a complex of non-specific changes in internal organs due to chronic fluoride intoxication. The accumulation of fluorine in the body initiates free radical oxidation, promotes the development of pathological processes in the heart against the background of an imbalance between pro- and antioxidants, and vascular endothelial dysfunction. Pathological activation of intima cells leads to unbalanced production of damaging factors, changes in the hemostasis system, and entails morphological and functional disorders of organs.
 Materials and methods. The experiments were carried out on one hundred twenty white male rats. A morphological study of the heart, blood vessels was performed out at 1, 3, 6, 9 and 12 weeks of chronic fluoride intoxication.
 Results. The 1st-3rd weeks of the experiment are characterized by the preservation of the morphological structure of the cardiac muscle against the background of the previously shown a compensatory activation of the components of the redox-signalling system, which provided a decrease in the intensity of free radical processes. With an increase in the duration of exposure to sodium fluoride (6–9 weeks) these mechanisms failure was noted, which was manifested by the development of degenerative changes in the myocardium, progressing up to the 12th week of the experiment. The described changes correlated with the development of endotheliosis, degenerative and fibroplastic processes, circulatory disorders in the vessels of the heart and other organs.
 Limitations. Histological findings are descriptive.
 Conclusion. The results obtained are of practical importance for the elaboration of effective methods for timely organ-protective prevention and correction of pathomorphological disorders, depending on the organ-specific features and duration of fluoride intoxication.

POSITIVE FEEDBACK LOOP OF ADHESION DISEASE: FIBRIN AND OTHERS

Adhesion disease is a common complication of abdominal operations, which is often manifested by acute adhesion obstruction of the intestine with a high rate of recurrence on surgical treatment. Mechanical damage to the peritoneum, which leads to uncontrolled leakage of blood from the damaged vessels and the formation of blood clots with the loss of fibrin at the site of damage, is recognized as the leading trigger of adhesion disease.The stability of the formed adhesions, their ability to grow and regenerate are in conflict with the known data on the mechanisms of the hemostasis system. The latter, as is known, consists of two divergent activation cascades, which ensure the blocking of hemorrhage in case of damage to vessels due to the formation of a fibrin clot with its subsequent splitting into large soluble blocks.An imbalance between the coagulation and fibrinolytic links of the hemostasis system causes various functional complications. The formation of adhesions can be considered as an extreme example of such an imbalance. This leads to the search for the reasons for the inefficiency of the fibrinolytic system in relation to fibrin deposits in adhesions.
 The aim of the work: study of the structure of fibrin deposits in adhesions using histological methods and infrared spectroscopy.
 Results and discussion. It is shown that adhesions of the peritoneum are a complex structure formed by protein and cellular components. The protein component is formed by fibrin and collagen, and the difference in the structure of these proteins from the native one with a pronounced content of β-structured aggregates is noted. The cellular component is mainly represented by fibroblasts - the main cells of connective tissue that synthesize collagen, elastin, proteoglycans and glycoproteins. Such composition ensures resistance of adhesions to fibrinolysis and their ability to regenerate.

Pathogenetic and clinical features of stroke associated with COVID-19

The novel coronavirus infection COVID-19 remains at the peak of current medical and social problems around the world. The incidence of the coronavirus infection remains at a fairly high level, despite new methods of diagnosis and treatment. The highest incidence of COVID-19 cases is observed among people with concomitant cardiovascular diseases. Such patients quite often develop COVID-19‑associated complications from various organs and systems, among which acute stroke is the most severe. The pathogenesis of stroke in COVID-19 is multifaceted. The key mechanisms for the development of acute cerebrovascular accidents in severe infections are the disruption of regulatory cortical and vegetative functions, hyperproduction of proinflammatory cytokines, and the disorder in the hemostasis system. This article analyzes current literature data on the features of the pathogenesis of stroke and its clinical course in patients with the novel coronavirus infection.

Indicators of the hemostasis system and markers of endothelial damage in patients with steatosis and liver fibrosis

Introduction. According to the analysis of indicators of the hemostasis system in liver pathology, there are multidirectional data in the literature, which may be associated with the examination of patients with varying degrees of severity and etiology of the process. Aim. The aim of the study was to study the indicators of hemostasis and markers of endothelial damage in patients with non-alcoholic steatosis and liver fibrosis of viral etiology. Materials and methods. A total of 64 people were examined. The first group included 32 patients with non-alcoholic liver steatosis on the background of obesity of 1–2 degrees, with an average age of 46.3 ± 4.3 years (12 men and 20 women). The second group consisted of 22 patients with liver fibrosis on the background of chronic hepatitis C (HCV) with an average age of 36.8 ± 4.7 years (12 men and 10 women). The control group included 10 practically healthy individuals with an average age of 38.9 ± 5.3 years without liver pathology. The number of platelets, platelet aggregation with ADP inducers, collagen and ristocetin, functional activity of Willebrand factor (vWF), coagulation hemostasis and fibrinolysis system, and serum concentration of vascular endothelial growth factor (VEGF) were determined. Statistical processing of the obtained data was carried out using the program “Stat2015”. Results. Induced platelet aggregation in steatosis and liver fibrosis significantly decreased with ADP agonists and collagen against the background of a normal platelet count. In both study groups, signs of endothelial damage with a tendency to increase the functional activity of vWF and VEGF hyperproduction were found. An elongation of thrombin time was also recorded, more significantly in patients with steatosis. Conclusion. Patients with non-alcoholic liver steatosis and liver fibrosis on the background of HCV are characterized by disorders in the vascular-platelet (endothelial damage and thrombocytopathy in the form of platelet hypocoagulation) and coagulation (hypocoagulation) links of hemostasis.

Clinical significance of ADAMTS-13/vWF axis in pregnant women at different trimesters of gestation

Introduction. The pandemic of a novel coronavirus infection has demonstrated the importance of assessing the ADAMTS-13/vWF axis in patients with COVID-19, because a decline in this ratio mirrors disease severity. However very few data in the global literature on crosstalk and ADAMTS-13/vWF levels in pregnant women remaining very contradictory are available. Taking into consideration an impact of the ADAMTS-13/vWF axis on prevalence of thrombosis and disorders in the hemostasis system, investigation of this issue is highly demanded.Aim: to assess the functioning of the ADAMTS-13/vWF axis during physiological pregnancy.Materials and Methods. A controlled non-randomized study was conducted: main group included 44 women with physiologically occurring pregnancies at I, II and III trimesters; the control group consisted of 45 healthy non-pregnant women. The plasma level of ADAMTS-13 inhibitor (ADAMTS-13:i), ADAMTS-13 antigen (ADAMTS-13:Ag), vWF antigen (vWF:Ag), and ADAMTS-13 activity (ADAMTS-13:Ac) as well as relevant ratio (ADAMTS-13:Ac/vWF:Ag) were measured.Results. It was shown that in parallel with increasing gestational age, significant changes occurred in the ADAMTS-13:Ac/vWF:Ag ratio. In main group, patients at II trimester were found to have level of ADAMTS-13:Ac/vWF:Ag 0.359 ± 0.121, in III trimester –0.253 ± 0.741, which significantly differed (p < 0.01) compared to control group with non-pregnant women (1,134 ± 0,308).Conclusion. Our study provides new insights into the functioning of the ADAMTS-13:/vWF axis in women with physiologically occurring pregnancy at I, II and III trimesters. Decline in ADAMTS-13:Ac was demonstrated along with increasing vWF:Ag level observed in parallel with increasing gestational age. Apparently, the progressive decrease of ADAMTS-13 concentration during pregnancy is associated with its increased consumption due to high vWF level. However, due to the small single-center patient cohort, further studies with larger-scale studies are needed.

Hemostasis parameters as prognostic biomarkers in gynecological cancer patients

Hypercoagulation is a typical condition for cancer patients. In addition, various arms of the hemostasis system become involved in tumor growth, invasion, metastasis, neoangiogenesis as well as immunoevasion. The magnitude of activated hemostasis is driven by tumor phenotype. Parameters characterizing coagulation, intensity of fibrinolysis processes, platelet aggregation and activation as well as endothelial activation mirror magnitude of hemostasis activation in oncological process, but may also be considered as candidate markers of tumor progression and predictors of oncological diseases outcome. This review summarizes the study data assessing a value of predictive hemostasis biomarkers for overall survival and response to therapy in oncogynecology and mammology. The most promising biomarkers have been identified and used in the future for risk stratification as well as personalized patient management.

Anticoagulant therapy in a hemodialysis patient at high risk of thrombotic and hemorrhagic complications. Case report

An attempt to preserve the knee joint in a patient on hemodialysis with stage IV lower limb ischemia with a high risk of thrombotic and hemorrhagic complications is presented. Multifocal atherosclerosis and extensive occlusion of the arteries of the lower leg ruled out the technical possibility of revascularization. The patient refused the proposed hip amputation. An attempt was made to perform amputation at the level of the lower leg. Required therapy aimed at the treatment and prevention of thrombotic complications, and optimization of microcirculation in the ischemic limb. For this purpose, a prolonged blockade of the sciatic and femoral nerves, combined anticoagulant therapy, and treatment with alprostadil were performed. Therapy with antithrombotic and vasoactive drugs was not effective and was complicated by the state of persistent hypocoagulation with an episode of bleeding. Amputation of the limb at the level of the thigh was performed according to vital indications after correction of hypocoagulation. The lack of clinical recommendations on anticoagulant therapy for critical lower limb ischemia in patients with stage 5 chronic kidney disease requires an individual approach to the choice of antithrombotic drugs and their doses, monitoring the state of blood coagulation using an integral method for assessing the hemostasis system thromboelastography.

Platelet Delta granules storage pool defi ciency in female patient with severe hemorrhagic syndrome

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.

Thromboelastometry for predicting hemostasis disorders after cardiopulmonary bypass during cardiac surgery

Introduction. Assessment of the state of the hemostasis system in cardioanesthesiology is carried out both clinically and using standard laboratory tests — thromboelastography (TEG), rotational thromboelastometry (ROTEM), or a combination of both. Both TEG and ROTEM are designed to detect disorders in the hemostasis system in real time. Aim – to evaluate the informativeness of ROTEM performed at the stage of cardiopulmonary bypass (CPB) before neutralization of heparin with protamine and to study the prognostic value of this study in assessing the risk of postoperative bleeding during cardiac surgery with a high risk of bleeding. Materials and methods. The assessment of the diagnostic significance of ROTEM studies at the CPB stage is based on the observation of 31 patients operated on from July to October 2018. The median age of these patients was 55 years (31–72 years). The criteria for inclusion of patients in the study were the performance of planned cardiac surgery with a high risk of bleeding: operations on the aorta, combined operations (coronary bypass surgery and/or surgery on the valve(s), multivalve correction), including repeated. Methods of descriptive statistics, correlation and comparative analyses, and ROC-analysis were used to assess the diagnostic and prognostic capabilities of ROTEM research during CPB against the back=-ground of high doses of heparin. Results. A statistically significant linear correlation was noted between A5 and MCF indicators in EXTEM, FIBTEM and PLTEM tests performed both during and after CPB. The results obtained indicate that determining the cause of bleeding and deciding on the choice of therapy is possible significantly earlier than the MCF indicator is determined, namely 5 minutes after the start of blood clotting in the ROTEM study. The informative value of ROTEM studies performed during CPB is shown, however, when interpreting the results, it is necessary to focus not only on the reference intervals, but also on the obtained cut-off levels for ROTEM parameters during CPB for early detection of hypofibrinogenemia or thrombocytopenia after CPB. Conclusion. ROTEM performed with the use of high doses of heparin during CPB is informative for the choice of pathogenetically justified therapy for possible bleeding.

COMPARISON OF THE IN VITRO ANTICOAGULANT ACTION OF PROTEASES SECRETED BY THE MICROMYCETE ASPERGILLUS OCHRACEUS AND CONTAINED IN SNAKE VENOM

The in vitro anticoagulant action of proteases secreted by the micromycete Aspergillus ochraceus L-1 and contained in snakes’ venoms (Protac® and RVV-X® preparations) was studied. The severity of the action of micromycete protease in relation to plasmas of humans and warm-blooded animals, as well as human plasmas de cient in certain factors of the hemostasis system, in comparison with snake proteases in reactions with chromogenic peptide substrates of activated protein C and factor X, as well as using the activated partial thromboplastin time (APTT) test. The optimal time of preincubation of the micromycete A. ochraceus L-1 protease with human blood plasma (3 min) and the concentration of the chromogenic peptide substrate of activated protein C (from 0.1 to 0.5 mg/ml) necessary for the correct determination of protein C with her help.

The clinical and prognostic role of changes in parameters of the hemostasis system and C-reactive protein in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19)

Aim. The purpose of our work was to find out the clinical and prognostic role of changes in hemostasis parameters and C-reactive protein (CRP) in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19). Materials and methods. 211 oxygen-dependent patients with COVID-19 were examined. To assess the prognostic role of changes in hemostasis parameters and CRP, patients were divided into groups: I group – 94 patients who recovered, II group – 117 patients who died. Subgroups: II-A subgroup – 35 patients with thrombotic complications and II-B subgroup – 82 patients without these complications. All patients were examined and received treatment according to the normative documents in force at the relevant time. Results. The frequency of thrombotic complications in oxygen-dependent patients with COVID-19 was 16.6 %, among which the most common were pulmonary embolism (6.6 %), myocardial infarction (6.2 %), and ischemic stroke (3.2 %). Lifetime diagnosis of thrombotic complications took place on the 18th [16.0; 24.0] day of illness in 45.9 % of cases. Deathtime diagnosis of thrombotic complications took place on the 24th [20.0; 28.0] day of illness in 54.1 % of cases. Lifetime pulmonary artery thromboembolism was diagnosed less frequently than ischemic stroke (p = 0.002) and myocardial infarction (p = 0.02). With the development of oxygen dependence and admission to the intensive care unit on the 9th [8.0; 11.0] day of illness, changes in the hemostasis system were characterized as prothrombotic with an increase above the reference values of fibrinogen and D-dimer in patients of all groups. CRP in patients with fatal outcomes of the disease, regardless of the development of thrombotic complications, was higher (p < 0.05) than in patients who subsequently recovered, and was accordingly in patients of the I group – 67.65 [41.20; 139.95] mg/l, in the II-A group – 122.2 [61.2; 178.0] mg/l, and in patients of the II-B group – 109.8 [56.3; 180.0] mg/l. In the dynamics of complex treatment after 5–7 days, the level of fibrinogen, D-dimer and CRP had a diagnostic value in predicting the further development of thrombotic complications. With an increase in the level of fibrinogen >4.6 g/l (AUC = 0.600, p = 0.042), D-dimer >2.1 μg/ml (AUC = 0.704, p = 0.001) and CRP >89.3 mg/l (AUC = 0.720, p < 0.001) the probability of developing thrombotic complications was significant. Conclusions. In dynamics of complex treatment of oxygen-dependent patients after 5–7 days, the levels of fibrinogen, D-dimer and C-reactive protein had consistent diagnostic value in predicting further development of thrombotic complications. Increased fibrinogen >4.6 g/l, D-dimer >2.1 μg/ml, and CRP >89.3 mg/l were important for predicting the risk of developing thrombotic complications.