Hemostasis System Research Articles

Hemostasis System and Plasminogen Activity in Retrochorial Hematoma in the First Trimester of Pregnancy.

(1) Background: The components of the fibrinolytic system and its main component, plasminogen, play a key role in the first months of pregnancy. The effect of autoantibodies interacting with plasminogen in the formation of retrochorial hematoma is unknown. The aim of our study was to determine the role of plasminogen and IgA, IgM, and IgG, which bind to plasminogen, in retrochorial hematoma. (2) Methods: Prothrombin time (PT), thrombin time (TT), partial activated thromboplastin time (aPTT), soluble fibrin-monomer complex (SFMC), D-dimer, plasminogen activity (%Plg), plasminogen concentration (Plg), and the levels of IgG (IgG-Plg), IgM (IgM-Plg), IgA (IgA-Plg) interacting with plasminogen were determined in plasma samples of 57 women with normal pregnancy and 16 with retrochorial hematoma. (3) Results: %Plg in plasma samples from women with retrochorial hematoma was significantly lower than in plasma samples from women with normal pregnancy. The diagnostic significance of %Plg in the ROC analysis was AUC = 0.85. A direct correlation was found between aPTT and the level of autologous IgM interacting with plasminogen. (4) Conclusions: A decrease in the activity of plasminogen in the blood serum of women in the first trimester of pregnancy may indicate disturbances in the hemostasis system and the formation of retrochorial hematoma. According to the results of the study, it is possible to recommend the determination of plasminogen activity in the management of pregnant women in gynecological practice.

Identification of a Phage Display-Derived Peptide Interacting with the N-Terminal Region of Factor VII Activating Protease (FSAP) Enables Characterization of Zymogen Activation.

Factor VII Activating protease (FSAP) has a protective effect in diverse disease conditions as inferred from studies in FSAP–/– mice and humans deficient in FSAP activity due to single-nucleotide polymorphism. The zymogen form of FSAP in plasma is activated by extracellular histones that are released during tissue injury or inflammation or by positively charged surfaces. However, it is not clear whether this activation mechanism is specific and amenable to manipulation. Using a phage display approach, we have identified a Cys-constrained 11 amino acid peptide, NNKC9/41, that activates pro-FSAP in plasma. The synthetic linear peptide has a propensity to cyclize through the terminal Cys groups, of which the antiparallel cyclic dimer, but not the monocyclic peptide, is the active component. Other commonly found zymogens in the plasma, related to the hemostasis system, were not activated. Binding studies with FSAP domain deletion mutants indicate that the N-terminus of FSAP is the key interaction site of this peptide. In a monoclonal antibody screen, we identified MA-FSAP-38C7 that prevented the activation of pro-FSAP by the peptide. This antibody bound to the LESLDP sequence (amino acids 30–35) in an intrinsically disordered stretch in the N-terminus of FSAP. The plasma clotting time was shortened by NNKC9/41, and this was reversed by MA-FSAP-38C7, demonstrating the utility of this peptide. Peptide NNKC9/41 will be useful as a tool to delineate the molecular mechanism of activation of pro-FSAP, elucidate its biological role, and provide a starting point for the pharmacological manipulation of FSAP activity.

Полиморфизм генов факторов системы гемостаза FII, FV, FGB, PAI-1 и тромбоцитарных рецепторов ITGА2, ITGB3 у пациентов с фибрилляцией предсердий

Фибрилляция предсердий (ФП) является наиболее распространенной аритмией в клинической практике, составляя примерно треть госпитализаций по поводу нарушений ритма сердца. ФП ассоциируется с увеличением риска смерти, инсульта и других тромбоэмболических осложнений (ТЭО), ухудшением качества жизни, снижением переносимости физической нагрузки и дисфункцией левого желудочка. Лабораторная диагностика предрасположенности к возникновению ТЭО проводится путём определения полиморфизма генов факторов системы гемостаза. Особый интерес представляет выявление случаев врождённой тромбофилии, возникающей в результате молекулярных дефектов в системе гемостаза или в процессах его ингибирования. В исследование были включены 41 здоровый доброволец в возрасте 53,4 ± 1,25 года и 52 пациента с пароксизмальной и персистирующей формами ФП в возрасте 60,20 ± 1,73 лет, из них у 8 пациентов (15,38%) произошло развитие ТЭО на фоне адекватной антикоагулянтной терапии. Генетические методы исследования включали выделение ДНК и исследование полиморфных вариантов генов системы гемостаза и тромбоцитарных рецепторов методом полимеразной цепной реакции в режиме real-time. Сравнительный анализ генотипов факторов системы гемостаза rs1799963 FII, rs6025 FV, rs1800790 FGB, rs1799899 PAI-1 и тромбоцитарных рецепторов rs1126643 ITGА2, rs5918 ITGB3 у пациентов с ФП и в контрольной группе достоверных различий не выявил. Исследуемые генетические полиморфизмы не ассоциированы с риском развития ТЭО у пациентов с ФП. Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for heart rhythm disorders. AF is associated with an increased risk of death, stroke and other thromboembolic complications, impaired quality of life, decreased exercise tolerance, and left ventricular dysfunction. Laboratory diagnosis of predisposition to the occurrence of thromboembolic complications is carried out by determining the polymorphism of genes of hemostasis factors. Of particular interest is the identification of cases of congenital thrombophilia resulting from molecular defects in the hemostasis system or its inhibition processes. The study included 41 healthy volunteers aged 53.4 ± 1.25 years and 52 patients with AF: paroxysmal and persistent forms at the age of 60.20 ± 1.73. Of these, 8 patients (15.38%) developed thromboembolic complications against the background of adequate anticoagulant therapy. Genetic methods of investigation included DNA isolation and examination of polymorphic variants of genes of the hemostasis system and platelet receptors using real-time polymerase chain reaction method. Comparative analysis of hemostasis system factors genotypes: rs1799963 FII, rs6025 FV, rs1800790 FGB, rs1799899 PAI-1 and platelet receptors: rs1126643 ITGA2, rs5918 ITGB3 in patients with atrial fibrillation and controls showed no significant differences. The studied genetic polymorphisms of hemostasis system factors and platelet receptors were not associated with the risk of thromboembolic complications in patients with atrial fibrillation.

Specific Changes in Hemostasis System Parameters during Extracorporeal Membrane Oxygenation in Patients with a Novel Coronavirus Infection

Extracorporeal membrane oxygenation (ECMO) is a method that makes it possible to compensate for critical changes caused by acute respiratory failure, with the ineffectiveness of treatment with rigid modes of artificial lung ventilation (ventilator) in patients with acute respiratory distress syndrome in intensive care units. The search for the optimal state of the hemostasis system is one of the main tasks in the treatment of critical patients in ECMO conditions.The objective: to study changes in hemostatic parameters in patients with COVID-19 undergoing ECMO and determine the need for their correction.Subjects and Methods. According to the inclusion and exclusion criteria, 100 patients were included in the study: 72 men and 28 women aged 26 to 75 years old, the median age made 55 years [47; 60]. VV-ECMO was performed in all observations. In 100% of cases, the cause of respiratory failure which required VV-ECMO was COVID-19-associated pneumonia.Results. 49 episodes of hemorrhagic complications and 76 episodes of thrombotic complications were recorded from the 1st to the 7th day from the moment of ECMO initiation. We found that the chance of developing thrombosis decreased by an average of 0.3% with an increase in the activity of antithrombin-3 by 1%. A statistically significant association of thrombosis risk was also found for prothrombin and prothrombin time.Conclusion. During the first 7 days of ECMO, patients with COVID-19 demonstrate the increase in APTT, prothrombin time and a decrease in the number of platelets, prothrombin activity, and fibrinogen concentration. The risk of thrombosis in this group of patients significantly decreases with the increasing activity of antithrombin-3 and prothrombin and increases with rising need of the higher dose of unfractionated heparin. The tactics of restrictive anticoagulant therapy when using unfractionated heparin can be taken into account as a way to reduce the risk of thrombosis and requires further research.

РОЛЬ СИСТЕМЫ ГЕМОСТАЗА В РАЗВИТИИ ДЕСТРУКТИВНОЙ ПНЕВМОНИИ У ДЕТЕЙ: ОБЗОР ЛИТЕРАТУРЫ И КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ

Complicated pneumonia in children remains an urgent problem in pediatrics because of increasing frequency of its current occurrence. The pathogenetic mechanisms of lung destruction have not been sufficiently studied as yet. The article presents an overview of current bibliographical data on the importance of the hemostasis system in the development of the infectious and inflammatory process in pneumonias. The clinical observations of various forms of destructive pneumonia in children are given as well.

Biochemical markers of thrombotic complications in the acute period of ischemic stroke

To study the profile of biochemical markers of the hemostasis system, to clarify their role and relationships in the pathogenesis of the development of thrombotic complications (TC) of ischemic stroke (IS) and the associated assessment of the possibilities of their diagnostic application. The study group included 302 patients (164 men, 138 women) who were admitted to the hospital with a diagnosis of IS within 24 hours of the onset of the disease. The diagnosis was confirmed by computed tomography. The average age of patients was 69 (5088) years. Blood was taken from all patients on the 1st day of the disease to determine the profile of analytes presumably associated with the pathogenesis of TC. Levels of homocysteine, protein C inhibitor, thrombomodulin, plasminogen, tissue plasminogen activator, urokinase, plasminogen activator type 1 inhibitor, t-PA/PAI-1 complex, vitronectin, plasmin-2-antiplasmin complex, D-dimer, fibronectin were determined in blood serum by ELISA. TC in the acute period of IS (up to 21 days) were recorded in 32 (10.6%, 95% CI 7.3714.3) patients, of which pulmonary embolism was observed in 27 (8.94%, 95% CI 5.9812.4) patients, deep vein thrombosis in 5 (1.66%, 95% CI 0.473.47) patients. The results of the study of a panel of specific proteins involved in pathogenetic processes accompanying necrosis of brain tissue in IS demonstrated that of the entire list of markers of the hemostasis system activation selected for the study, the most significant are: the concentration of fibronectin in the prognosis of the absence of TC with a threshold value of more than 61 mkg/ml and OR 4.4 (95% CI 1.512.9, p=0.011), and the concentration of the t-PA/PAI-1 complex in the prognosis of the development of TC with a threshold value of more than 14 ng/ml and OR 11.3 (95% CI 1.18109.3, p=0.03). The significance of the t-PA/PAI-1 complex and fibronectin as markers of TC in IS may be due to a violation of the activation processes of the fibrinolytic link of hemostasis and the accumulation of non-deposited compounds that damage the vascular wall.

Korelasi HbA1c, APTT dan PT Pada Pasien Diabetes Militus tipe 2 Sebagai Prediktor Hiperkoagulasi Di Rumah Sakit Umum Gambiran Kota Kediri

The state of chronic hyperglycemia in DM can cause an increase in blood clotting factor levels, these affect the hemostasis system, and become the basis for the emergence of a hypercoagulable state in DM patients, hypercoagulation can be identified by examination of clotting factors, these are PT and APTT. The purpose of this study was to determine the relationship between HbA1c, APTT, and PT in diabetes mellitus patients as a predictor of hypercoagulation. The design in this study uses a cross-sectional study. The population in this study were 108 DM patients at the Gambiran General Hospital, Kediri City with a total sample of 20 Type 2 Diabetes Mellitus patients, Sampling technique was purposive with inclusion criteria: type 2 DM patients with HbA1c levels > 6.4% and exclusion: Type I DM patients, Type 2 DM patients with anticoagulants treatment and type 2 DM patients with liver disease. The average HbA1c level was 9.35%, the maximum level was 14% and the minimum level was 6.5%. The average PT time was 12.6 seconds with the longest time being 14.9 seconds and the fastest time being 10.4 seconds. The results of the APTT examination have an average of 26.2 seconds with the longest time being 35.2 seconds and the fastest time being 22.7 seconds. HbA1c with APTT has no correlation, this is indicated by a p-value of 0.794 or > 0.05 and r = 0.062. HbA1c with PT there is a correlation with p-value 0.005 or <0.05 and a moderate level of correlation r = 0.598. The conclusion of this study, HbA1c in type 2 DM patients did not correlate with APTT, whereas have positively correlated with PT that it could be interpreted when HbA1c levels increased then the PT time would be prolonged or hypocoagulation

Structural and functional changes in erythrocytes associated with the development of thrombosis and disorders of hemostasis

The data of clinical and experimental studies of the last decade force us to reconsider the role of red blood cells in the development of thrombosis and disorders of the hemostasis system. This area is of particular relevance during the COVID-19 pandemic. The purpose of the review is to present data on the structural and functional changes in erythrocytes, on changes in their number associated with the development of thrombosis and hemostasis disorders, including in patients with coronavirus infection. The article presents the results of scientific research devoted to the study of morphological and functional changes in red blood cells that affect hemostasis and thrombosis. These changes include erythrocyte number or hematocrit (which modulates blood rheology through blood viscosity) and qualitative changes such as deformability, erythrocyte aggregation, expression of adhesive proteins and phosphatidylserine, release of extracellular microvesicles, hemolysis, piezo receptor status, modulation of nitric oxide bioavailability. Changes in the parameters of erythrocytes that occur during blood storage are shown, with possible thrombotic consequences during blood transfusion. The most recent research concerns changes in red blood parameters during SARS-CoV-2 infection that are associated with the development of thrombosis: virus attachment and amplification of viral proteins in erythropoiesis progenitor cells; activation of stress erythropoiesis with an increase in nuclear erythrocyte cell percentage up to 42 %; activation of the processes of oxidation of the protein band 3 with its excessive cleavage, oxidation and cleavage of the alpha-chain of spectrin, ankyrin; changes in the lipid architecture of the membrane and a decrease in the activity of erythrocyte antioxidants, which mediate disturbances in cell deformability and impaired ATP release; reducing the ability of red blood cells to secrete nitric oxide; decrease in the level of sphingolipids of the erythrocyte membrane; excessive production of microvesicles with tissue factor; an increase in erythrocyte rigidity with impaired release of intraerythrocyte nitric oxide due to SARS-CoV-2 virus attacking the hemoglobin 1-beta chain and porphyrin capture with potential heme inhibition; an increase on the surface of erythrocytes expression of activated complement components C3b and C4d, immunoglobulin IgG, which worsens cell deformability; attachment of erythrocytes through the Toll-like receptor 9 to neutrophil extracellular traps, which contributes to thrombosis; increased presentation of phosphatidylcholine on erythrocyte membranes, which facilitates the assembly of the tenase and prothrombinase complexes, contributing to the production of thrombin, an increase in intracellular calcium levels with stimulation of the formation of microvesicles with prothrombotic potential. The presented data indicate a significant role of changes in erythrocyte parameters in the development of hemostasis disorders, especially during the COVID-19 pandemic, which makes red blood cells a target for therapy and suggests a change in the emphasis of management tactics for patients with thrombosis.

PROPHYLAXIS COMPLEX OF PLACENTAL DYSFUNCTION AFTER THE INFLUENZA TRANSFERRED IN THE EARLY STAGES OF PREGNANCY

Aim of the research: to increase the effectiveness of tactics for the presence of placental dysfunction in the background of influenza by developing and implementing a pathogenetically sound set of treatment and prevention measures.
 Materials and methods. Test the effectiveness of the proposed set of treatment-and-prophylactic measures, 80 pregnant women were selected after influenza transferred to early pregnancy: 40 women whose pregnancies were optimized tactics (main group) and 40 women (comparison group), which were conducted according to clinical protocols of the Ministry of Health. The cytotoxicity of natural killers (NK) was assessed by flow cytometry. The level of cytokines in peripheral blood was studied by enzyme-linked immunosorbent assay: interleukin-1 (IL-1), interleukin-10 (IL-10). The study of 25-hydroxyvitamin D, 25- (OH) D was performed by enzyme-linked immunosorbent assay. Determination of serum hormones was performed using standard kits for immunoradiometric determination.
 Results. Homeostasis in the first trimester of pregnancy after influenza is characterized by disorders that reflect further plantar dysfunction: a list of NK cytotoxicity, proinflammatory changes in the cytokine profile, the procoagulant state of the hemostasis system. Optimization of conservation in such tactics is the use of pathogenetic and preventive measures, treatment and prevention measures to prevent placental insufficiency and reduce the negative effects of hyperimmune reactions (aspirin, dipyridamole, progestogens, intravenous immunoglobulin, vitamin D). The use of the recommended set of measures has a positive effect on hormonal functions of the placenta (normalization of progesterone and estradiol levels). Immunity also improved: one month after starting treatment with NK lysis 1:10 decreased from 24 [15; 30] to 17 [13; 21] (p <0.05), the balance of the cytokine profile was manifested in a decrease in the ratio of IL-1 / IL-1 from 1.36 [1.12; 2.51] to 0.82 [0.42; 1.16] (p <0.05). The proportion of women with suboptimal vitamin D levels decreased significantly from 87.5% to 37.5% (p <0.05), and in cases of deficient conditions it was possible to bring the level of vitamin D in the blood to optimal or suboptimal. Reduction of Willebrand factor from 1.54 [1.38; 1.74] to 0.92 [0.68; 1.08] IU / ml (p <0.05) indicates an improvement in endothelial function, which in turn creates favorable conditions for the development of the feto-placental complex. The use of the recommended management of pregnant women after influenza in early pregnancy has reduced the incidence of placental insufficiency by almost 2 times, which was diagnosed in 13 (35.0%) women in the main group against 25 (62.5%) patients in the comparison group p <0.05).
 Conclusions. The use of the recommended set of measures has a positive effect on hormonal functions of the placenta (normalization of progesterone and estradiol levels), immune status (reduction of NK cytotoxicity, cytokine profile balance), elimination of vitamin D deficiency and reduction of procoagulation potential of hemostasis. Creating favourable conditions for the development of gestation can reduce the incidence of placental insufficiency by almost 2 times to 35.0% vs. 62.5%.

Pathogenetic significance of antiphospholipid antibodies in the development of placenta-associated complications in pregnant women with thrombocytopenia

BACKGROUND: Thrombocytopenia is one of the most common cytopenic syndromes that complicate pregnancy. It is considered a typical hematological criterion and the second most common manifestation of antiphospholipid syndrome. In recent years, the relationship between the development of thrombotic and placenta-associated pregnancy complications and the circulation of antiphospholipid antibodies has been actively studied, which makes it necessary to search for new methods for hemostasis correction and for prevention of the development of obstetric complications.
 AIM: The aim of this study was to assess the incidence of antiphospholipid antibodies in pregnant women with thrombocytopenia in order to determine the risk of obstetric complications and adverse pregnancy outcomes depending on the presence of antiphospholipid antibodies in the examined women.
 MATERIALS AND METHODS: 299 pregnant women were included in this multicenter prospective study: the main study group (n = 249) consisted of patients with thrombocytopenia, and the control group (n = 50) comprised women with normal platelet counts during a physiological pregnancy. All participants underwent a complete clinical and anamnestic examination and a study of the hemostasis system. To determine antibodies to cardiolipin, beta-2 glycoprotein 1, annexin V, and prothrombin (IgG/IgM/IgA), we performed enzyme-linked immunosorbent assay in 84 pregnant women with thrombocytopenia and in 25 women in the control group. Lupus anticoagulant was determined in 123 pregnant women of the main group and 25 women in the control group using an ACL-200 coagulometer (Instrumentation Laboratory, Spain).
 RESULTS: A comparative analysis of antiphospholipid antibodies detection has shown that in pregnant women with thrombocytopenia, lupus anticoagulant was detected in every third case (35.8% of cases, 44/123 women), which is more common than in the control group (8.0% of cases, 2/25 women; p = 0.008). Antibodies to beta-2 glycoprotein 1 were detected in pregnant women with thrombocytopenia in every fourth case (27.4% of cases, 23/84 women), and in the control group only in 4% of cases (1/25 women; p = 0.013). Antibodies to cardiolipin were also more often detected in pregnant women with thrombocytopenia (23.8% of cases, 20/84 women) compared to the control group (4% of cases, 1/25 women; p = 0.040). Based on the data obtained with V Cramer, we established medium-strength direct correlations between criterial antiphospholipid antibodies circulation and the development of placenta-associated complications of pregnancy (p 0.05; 0.2 V 0.4). We also identified statistically significant risks of developing placenta-associated complications in pregnant women with circulating antiphospholipid antibodies (95 % confidence interval excludes 1).
 CONCLUSIONS: Thrombocytopenia during pregnancy develops more often in women with antiphospholipid antibodies. Antiphospholipid antibodies circulation elevates coagulation potential and activates intravascular coagulation, resulting in an increased risk of placenta-associated complications of pregnancy, which requires hemostasis correction.

THROMBIN GENERATION TEST AS AN INTEGRAL ANALYSIS OF THE HEMOSTASIS SYSTEM: TECHNICAL CAPABILITIES AND APPLICATION IN LABORATORY PRACTICE

This review is devoted to one of the integral tests for assessing the hemostasis system — the thrombin generation test (TGT), its technical characteristics, problems in standardization and possible clinical use. Evaluation of thrombin generation (TG) is more sensitive to changes occurring in the hemostasis system, since it takes into account the effect of both procoagulant and anticoagulant factors in the process of TG. It is important to note that there are options for setting TGT in platelet-rich plasma or in whole blood, which brings the researcher closer to in vivo conditions. However, despite the obvious advantages of this analysis when compared with routine screening tests for assessing the hemostasis system, there are number of limitations, including the lack of standardization, which does not currently allow the introduction of TGT into clinical practice. This review discusses the technical characteristics of TGT and variants of reagent kits depending on the clinical task, and provides the results of recent studies in the field of clinical use of TGT, demonstrating the prospects of GT analysis for assessing the risk of both hemorrhagic complications and thrombotic events.

Hypochlorite-induced oxidative modification of fibrinogen

Fibrinogen (FG) is a protein that plays a key role in the hemostasis system and is most susceptible to oxidative modification compared to other plasma proteins. FG undergoes post-translational modifications that can potentially disrupt its structure and function.For the first time, using high resolution mass spectrometry (HPLC/MS/MS), the consequences of hypochlorite (HOCl)- induced FG oxidation were studied, and a list of FG amino acid residue oxidatively modifications. Samples of nonoxidized and treated with 50 μM HOCL fibrinogen were analyzed by mass spectrometry and it was found that many amino acid residues localized in all three polypeptide chains and the main structural elements of fibrinogen, with the exception of the E region, are involved in oxidation.Thus, the amino acid residues localized in the E region, which are involved in thrombin binding, were not subject to oxidative modification, which indicates the preservation of the thrombin-binding sites of the fibrinogen molecule during oxidation. The αС region contains the largest number of oxidizing sites, which confirms the hypothesis that this region can serve as a trap for reactive oxygen species (ROS) molecules.

Clinical course and features of the diagnosis of infectious endocarditis in the elderly

Infectious endocarditis is a formidable disease characterized by an extremely unfavorable prognosis in its natural course. Analyzing the literature data, it can be noted that the frequency of infectious endocarditis in the Russian Federation has relatively high prevalence rates in relation to other countries. Currently, the problem of early diagnosis of infectious endocarditis remains relevant. Despite the fact that the diagnosis of infectious endocarditis has improved, mainly as a result of the improvement of echocardiographic and microbiological approaches, the introduction of new antibacterial drugs and cardiac surgery technologies into clinical practice, the clinical picture, changes in laboratory parameters can lead to the exclusion of immuno-inflammatory, rheumatic, oncological, hematological diseases, complicating and delaying the diagnosis of infectious endocarditis. The first clinical signs of infectious endocarditis may be nonspecific, and the disease remains unrecognized for weeks or even months. The high frequency of thrombotic, thrombohemorrhagic complications indicates profound changes in the hemostasis system in infectious endocarditis and the need to disclose the pathogenesis of these disorders. The combination of these factors led to the late diagnosis of this disease in the patient. The aim of the study is to study the possibility of improving the results of diagnosis and therapy of patients with infectious endocarditis in clinical practice.

D-dimers-"Normal" Levels versus Elevated Levels Due to a Range of Conditions, Including "D-dimeritis," Inflammation, Thromboembolism, Disseminated Intravascular Coagulation, and COVID-19.

D-dimers reflect a breakdown product of fibrin. The current narrative review outlines how D-dimers can arise in normal individuals, as well as in patients suffering from a wide range of disease states. D-dimers in normal individuals without evident thrombosis can arise from background fibrinolytic activity in various tissues, including kidney, mammary and salivary glands, which ensures smooth flow of arising fluids where any blood contamination could be immediately lysed. In addition, healthy individuals can also regularly sustain minor injuries, often unbeknown to them, and wound healing follows clot formation in these situations. D-dimers can also arise in anxiety and following exercise, and are also markers of inflammation. Lung inflammation (triggered by microbes or foreign particles) is perhaps also particularly relevant, since the hemostasis system and fibrinolysis help to trap and remove such debris. Lung inflammation in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may contribute to D-dimer levels additive to thrombosis in patients with COVID-19 (coronavirus disease 2019). Indeed, severe COVID-19 can lead to multiple activation events, including inflammation, primary and secondary hemostasis, and fibrinolysis, all of which may contribute to cumulative D-dimer development. Finally, D-dimer testing has also found a role in the diagnosis and triaging of the so-called (COVID-19) vaccine-induced thrombotic thrombocytopenia.

Thrombosis in patients with hereditary fibrinogen deficiency

Introduction. In most cases, in patients with hereditary fibrinogen deficiency, clinical manifestations are represented by bleeding of varying intensity and localization. However, the clinical picture of hereditary fibrinogen deficiency can also be represented by thrombosis.Aim — to characterize the detected mutations in fibrinogen genes and to analyze prothrombotic factors in patients with hereditary hypofibrinogenemia and thrombosis.Materials and methods. Forty-nine patients with hereditary hypofibrinogenemia were observed, of which 46 patients had no history of thrombosis and 3 patients had a confirmed history of thrombosis. These 3 patients made up the study group.Results. Heterozygous mutations were found in all 3 patients in the fibrinogen gamma chain gene (FGG), one of them had a previously undescribed deletion g.2653_2684+211del, p.(Asp167Glufs*2), which removes 32 terminal nucleotides of the fifth exon of the FGG gene and leads to the formation of a stop codon in place of amino acid 168. In two other patients, there were missense mutations c.1140T>A, p.(Cys365Ser) and c.1114A>T, p.(Asp356Val), which can determine the thrombogenic properties of the altered protein structure of fibrinogen. Other prothrombotic factors were also identified: genetic polymorphisms of low thrombotic risk, surgery, taking combined oral contraceptives.Conclusion. Hereditary fibrinogen deficiency does not play a protective role in relation to the development of thrombosis and may cause the development of thrombosis, which is associated with its multifunctional role in the hemostasis system. The pathogenesis of thrombosis in patients with hereditary hypofibrinogenemia is multifactorial and may be associated with the characteristics of the main protein defect and the coexistence of hereditary and acquired thrombotic risk factors (surgical interventions, taking combined oral contraceptives, etc.).

Coagulation Disorders in Infective Endocarditis: Role of Pathogens, Biomarkers, Antithrombotic Therapy (Systematic Review)

The issue of antithrombotic therapy in patients with infective endocarditis has been studied for over 75 years. During that time studying of pathogenesis of the disease and its embolic complications, lead to the introduction of the concept of “immunothrombosis”. That mechanism allows infective agents (mostly bacteria) to be cloaked from the immune system and to multiply freely, leading to growth of vegetation, thus resulting in higher chance of fragmentation. Small-scale experimental and clinical studies on the correction of hemostatic disorders in infective endocarditis, that were performed in 20th century, didn’t show any significant results, that could affect clinical practice. However, reinterpretation of available data on coagulative system will allow to have elements of hemostasis as an application point in treating infective endocarditis. The article will discuss latest insights on the role of hemostasis system in pathophysisology of infective endocarditis, its effects on the development of the embolic complications, perspectives for diagnostics and treatment.

Specific Parameters of Intraoperative Changes in the Hemostasis System during Liver Resection in Children

The objective: to determine severity of changes in the hemostasis system in children occurring at main stages of liver resection as well as the need for their intraoperative correction.Subjects and Methods. A single-center prospective pilot study of coagulogram and rotational thromboelastometry values was conducted in 25 children aged 0–11 years old with hepatoblastoma after a course of chemotherapy according to the PRETEX IV regimen who underwent hemihepatectomy.Results. There were no statistically significant differences in parameters of the ROTEM tests both when comparing groups and when comparing hemihepatectomy stages within the same age group of patients. At the beginning of the separation of the liver parenchyma INTEM: CT 200.00 (186.00; 238.00), CFT 88.00 (83.00; 139.00), MCF 54.00 (51.00; 61.00), ML 0.00 (0.00; 5.00) in Group I, CT 191.00 (179.00; 199.00), CFT 84.00 (79.00; 103.00), MCF 60.00 (58.00; 64.00), 4,00 (3.00; 9.00) in Group II, respectively, p > 0.05. After separation of the liver parenchyma INTEM: CT 201.00 (161.00; 237.50), CFT 93.00 (95.00; 112.00), MCF 54.00 (52.50; 59.50), ML 6.00 (2.00; 10.00) in Group I, CT 229.00 (201.00; 285.00), CFT 93.00 (78.00; 177.00), MCF 59.00 (49.00; 60.00), ML 5.00 (5.00; 10.00) in Group II, respectively, p > 0.05.Conclusion. After chemotherapy courses, children aged 0–11 years suffering from hepatoblastoma, maintain normal functional activity of the hemostasis system at all stages of surgical treatment. In children under 11 years of age, routine hemostasis correction with blood products and prothrombin complex factor concentrate is not required during the main stages of hemihepatectomy.

Male menopause: impact on hemostasis and treatment

Andropause, which is analogous to menopause in women, on average occurs at the age of 45–50 years in men. It is at this age that the increase in the likelihood of developing thrombosis and thromboembolism in males occurs. Nowadays, there is a large number of ways to restore testosterone levels, which will allow avoiding increased blood clots. The aim of the work was to consider the effects of testosterone on the hemostasis system, possible treatment options for male menopause, as well as the main side effects that occur during treatment with testosteronepreparations.

The Role of Vascular-Platelet Hemostasis Disturbances in the Genesis of Respiratory Failure in Patients with COVID-19

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

Using the posterior TAP block for postoperative analgesia for major liver surgery in pediatrics

Anesthesiological provision of pediatric liver surgery is associated with problems related to perioperative analgesia. Standard methods of anesthesia can have contraindications and complications.The objective: To evaluate the safety and efficacy of the posterior TAP block for postoperative analgesia in pediatric liver surgery.Subjects and Methods. A prospective, single, blind, placebo-controlled pilot study was conducted. The participants were children aged 2 to 7 who underwent liver resection. The patients were divided into groups. In Control Group, combined anesthesia was performed. In Study Group, it was combined with a bilateral posterior TAP block. Pain in the postoperative period was assessed by the FLACC scale.Results. The intensity of pain in the postoperative period was higher in Control Group. More patients required tramadol administration in Control Group. There was no difference in the occurrence of the PONV syndrome. No complications associated with the block were noted.Conclusion. The posterior TAP block has a clinically significant analgesic effect and can be used for perioperative pain relief during pediatric liver surgery. This method is relatively safe. Impaired hemostasis system is not an absolute contraindication to a TAP block.