Disorders Of Hemostasis Research Articles

Protocolo diagnóstico de las alteraciones de la hemostasia

Diagnostic protocol for hemostasis abnormalities: The presence of hemorrhagic symptoms and/or abnormalities on a basic coagulation test is on many occasions the consequence of an underlying coagulopathy. It is very important to know how to interpret whether hemorrhagic symptoms are pathological or not and what studies must be performed in the laboratory in order to diagnose and confirm a hemostasis disorder.

Skin and vascular lesions in chronic hepatitis: clinical, laboratory and morphological aspects

The study of 184 patients with chronic hepatitis (CH) of diff erent etiology was carried out. Skin and vascular lesions were detected in 129 of them. A comparative assessment of clinical manifestations of skin and vascular lesions, assessment of morphological changes according to the bio-PSIA of the skin and muscle fl ap, evaluation of hemostasis indicators, immunological tests depending on the etiology of HCG was carried out. It was found that the most common cause of skin and vascular lesions are various forms of chronic viral hepatitis (CVI B+C) and CVI B. The predominant morphological feature of lesions is mixed-cell vasculitis of small and medium vessels. Analysis of hemostasis indicators and immunological tests showed an important role in the development of vasculitis in HVG immunological disorders and of disorders of hemostasis.

Characteristics of clinical and anamnestic data and of condition of primary hemostasis in chronic diseases of liver in children

Aim. To perform a comparative analysis of clinical and anamnestic data and of the condition of primary hemostasis in chronic liver diseases in children and to identify additional informative diagnostic criteria that reflect severity of the course of autoimmune hepatitis (AIH) and chronic viral hepatitis C (CVHC) in children.
 Materials and Methods. 91 Patients from 3 to 7 years old were examined, of them: 60 children with AIH and 31 children with CVHC. The control group included 15 children of I and II health groups. In all the patients the clinic-anamnestic data and the condition of the primary hemostasis were evaluated. Concentrations of endothelin-1 and homocysteine, activity of Willebrand factor, amount of platelets and their aggregation activity were determined.
 Results. AIH is characterized by a more aggressive course as compared to CVHC manifested by clinical signs of a severe liver damage, significant biochemical changes and a high rate of fibrosis within the first two years. In all the children there were found disorders in the primary hemostasis interrelated with the main clinical and laboratory syndromes reflecting the severity of the liver damage. AIH is characterized by a higher concentration of homocysteine (р=0.007) and of the activity of Willebrand factor (р=0.037) in comparison with CVHC.
 Conclusions. Signs of a severe liver damage are not characteristic of children with CVHC in the first 10 years of the disease, however, disorders of the primary hemostasis are present characterized by hyperaggregation of platelets and by endothelial dysfunction. AIH in children is characterized by aggressive course and more pronounced deviations of the primary hemostasis in comparison with CVHC. In AIH and CVHC, the pathology of the primary hemostasis is closely related to some clinical-laboratory symptoms that reflect severity of the disease.

COVID-19, hemostasis disorders and risk of thrombotic complications

The spread of a new coronavirus infection worldwide since the end of 2019 has becomes a pandemic. Thrombotic complications are the leading cause of death in this disease. After entering the human body, the virus starts a cascade of reactions leading to the development of a cytokine storm, activation of all parts of the hemostasis and complement systems and other changes that result in disturbances in the circulation system with the development of multiple organ failures. Numerous studies have shown that a predictor of a severe course of COVID-19 is a sharp increase of D-dimer concentration in the blood and rise of some other markers of hemostasis activation. Based on the pathogenesis, the developed schemes for the prevention and treatment of COVID-19 severe complications include low molecular weight heparins (LMWH) which are also recommended for an outpatient COVID-19 patient. The prescription of low molecular weight heparin, the duration of their use and doses should be decided on the basis of a risk assessment of factors for each individual patient in combination with laboratory monitoring.

Transfusion management of abdominal delivery in pregnant women at high risk of bleeding with hemostasis control

Objective of the study . Optimization of transfusion support of abdominal delivery in pregnant women at risk of obstetric haemorrhage using monitored management of haemostasis disorders. Study materials. The study group consisted of 24 women of 23-47 years old with abnormal placental invasion (API) and bleeding during caesarean section at a gestational age of 32-36 weeks. Group 1 consisted of 14 patients, who were injected with tranexamic acid as part of combined therapy; Group 2 consisted of 10 women, who were injected with aminomethylbenzoic acid as part of combined therapy. Results. All patients received instrumental autoerythrocyte reinfusion. Three patients of Group 1 (21.4%) with refractory bleeding received recombinant coagulation factor VIIa (Coagil, Russia) at a dose of 60 pg/kg body weight (average dose 6.6 ± 1.4 mg), a decrease in bleeding was observed, the operative treatment was completed in the form of metroplasty. In the early stages of bleeding, eight patients were injected with a prothrombin complex concentrate of 600-1,200 IU before administration of fresh-frozen plasma (FFP), which allowed to reduce the volume of donor FFP in these patients. The study of hemostasis showed a very high inverse relationship between extent of blood loss and fibrinogen level in the groups of patients. Conclusion. The use of factor VIIa in refractory major obstetric haemorrhage (MOH) in patients with API allows to reduce the blood loss, perform metroplasty, and preserve the woman’s fertility. Patient blood management (PCM) in pregnant women with API makes it possible to conduct organ-preserving treatment in 91.7% of women.

Effect of perioperative infusion therapy on the functional state of the hemostatic system in patients with concomitant coronary heart disease

Background. The choice of the infusion therapy regimen in the perioperative period remains a complex and controversial issue of modern anesthesiology. This is especially true for elderly patients with concomitant cardiovascular diseases, primarily coronary heart disease (CHD). Excessive fluid restriction in the perioperative period during the intervention can contribute to the development of arterial hypotension and hypoperfusion of vital organs. At the same time, excessive fluid intake in these patients is dangerous in terms of developing complications such as decompensation of heart activity, ischemic myocardial damage. There are many factors of the perioperative period that affect the processes of fluid metabolism in the body, the state of hemodynamics and other vital functions. Among them, the most significant factors are operational stress, features of the underlying disease and surgical intervention, the influence of anesthetics, the functional state of the cardiovascular system, kidneys, etc. One of the insufficiently considered factors that may influence the choice of infusion therapy, in our opinion, is the functional state of the hemostatic system in the preoperative period.
 Objective. To investigate the effect of perioperative infusion therapy on the functional state of the hemostatic system in patients with concomitant CHD.
 Materials and methods. A total of 92 patients who underwent abdominal surgery under combined general anesthesia with a ventilator were examined. The average age of patients was 61±12 years; risk on the ASA scale – II-III; risk of cardiac complications on the RCRI – 1-3; risk of thrombosis on the Caprini scale – 6.5±0.1. The functional state of platelets was assessed using the platelet aggregation analyzer AR 2110 (Belarus); the state of plasma hemostasis was assessed using standard coagulogram indicators.
 Results and discussion. When studying platelet aggregation in the initial state, significant fluctuations in the studied parameters were found from significant hypoaggregation to significant platelet hyperaggregation. For further analysis and differential correction, patients were divided into three groups depending on the degree of platelet aggregation. Group 1 included 22 patients with established hypoaggregation, 2nd group – 38 patients with established normal platelet aggregation, and 3rd group – 32 patients with platelet hyperaggregation. The coagulogram in the majority of patients in the initial state characterized normocoagulation or a tendency to hypercoagulation. Correction of changes in primary hemostasis was performed using infusion therapy, depending on the initial data of platelet aggregation. In the group with greegreece platelets was conducted infusion therapy with the liberal type – 5-10 ml/kg/h for intraoperative stage and 20-25 ml/kg/day after surgery; in the group with hoareau for restrictive type an average of 3-5 ml/kg/h for intraoperative stage and 20-25 ml/kg/day after surgery; in the group with normoergic the relatively restrictive type that was 5-7 ml/kg/h intraoperatively; 25 ml/kg/day after surgery. For specific correction of platelet-vascular hemostasis, etamzilate 12.5 % 4.0 ml was used in group 1 patients before surgery and later 4.0 ml three times a day; in group 3 patients, pentoxifylline 2 % 5.0 ml twice a day. Thromboprophylaxis with low-molecular-weight heparins in the perioperative period was performed in all patients according to current recommendations. As a result of this approach to the correction of established disorders of platelet-vascular hemostasis, a clear trend towards normalization of the studied parameters was established already at the intraoperative stage, this trend persisted a day after the operation. Thus, the indicators of platelet aggregation in group 1 patients at the intraoperative and early postoperative stages were 68.2 (59.5; 78.1) and 63.6 (60; 72.6); in group 3 patients – 79.7 (75.3; 94.2) and 74.6 (59.2; 83.4), respectively.
 Conclusions. Individualized infusion and pharmacological therapy allows correction of disorders of platelet-vascular hemostasis in patients with concomitant CHD, which may be useful for reducing the risk of thrombotic complications.

COVID-19 and vascular disorders (literature review)

The review describes pathogenesis of the disease caused by the new SARS-CoV-2 virus. It infects the human cells by linking angiotensin-converting enzyme-2 (ACE2) and a number of other receptors. The virus imbalances the renin-angiotensin system, results to vasoconstriction and acts like pro-inflammatory agent. ACE2 is exposed on the alveolar epithelium cell surface. It is the main gates for virus entering and damaging of the respiratory system resulted in an acute respiratory distress syndrome. The injuring of the pulmonary vessel endothelium is the most important part of the COVID-19 pathogenesis. ACE2 of the endothelial and smooth muscle cell surface upon the SARS-CoV-2 infection facilitates the injury of cardiovascular system. The development of endotheliitis induced by «cytokine storm» leads to the main signs of the disease and the multiple disorder of the microcirculation. The investigation of that condition has a prognostic value and determines the treatment especially in critically ill patients. Systemic endothelial dysfunction upon the COVID-19 largely triggers the hemostasis disorders. High activity of platelets adhesion and aggregation, blood coagulation in died COVID-19 patients, disorder of fibrinolysis system functional activity could be induced by the endothelium activation. The unchanged anticoagulation blood activity in the COVID-19 patients distinguishes them from the patients with disseminated intravascular coagulation. Monitoring of the hemostasis system in COVID-19 is important for the disease severity assess and its prognosis, for justin-time correction of detected deviations.

Редкий случай гиподисфибриногенемии у пациента без гематомезенхимальной дисплазии

Фибриноген и коллаген являются важнейшими протеинами межклеточного матрикса, оказывающие прямое влияние как на дифференцировку мезенхимальных стволовых клеток, так и на остеогенез. Кроме того, в клинической практике встречаются случаи протекания данного синдрома не в классическом виде, которые требуют более углубленного изучения звеньев патогенеза и разработки оптимальной коррекции заболевания. Нами проведен поиск литературных данных по ключевым словам в базах данных PubMed, UpToDate, BMJ. Представлен обзор современных научных данных и результаты наблюдения редкого клинического случая у пациента с гиподисфибриногенемией с проявлениями асептического некроза головок бедренных костей без гематомезенхимальной дисплазии. Заключение: В целом, в настоящее время подробно изучены различные аспекты клинико-биохимического патогенеза аномалий фибриногена, но остаются «белые пятна» в изучении тонких патогенетических механизмов на молекулярно-генетическом уровне, а именно: катаболизм белка, реакции раздельного синтеза отдельных полипептидных цепей фибриногена в разных тканях. Остается нерешенным вопрос о целесообразности применения корригирующих гемостаз препаратов таргетного действия при отсутствии у пациента выраженных тромботических и геморрагических проявлений. Fibrinogen and collagen are the most important intercellular matrix proteins that directly effect on the differentiation of mesenchymal stem cells and osteogenesis. In addition, there are non-classical cases of this syndrome that require indepth study of pathogenesis and optimal disease correction. We examined literature data by keywords in databases PubMed, UpToDate, BMJ. We presented a review of current scientific data and observation results of a rare clinical case in a patient with hypodysfibrinogenemia without hematomesenchymal dysplasia with manifestations of aseptic necrosis of femoral heads. Conclusions: In general, various aspects of clinical and biochemical pathogenesis of fibrinogen abnormalities are currently studied in detail, but there are “white spots” in the study of sophisticated pathogenetic mechanisms at the molecular genetic level, namely protein catabolism, the reaction of separate synthesis of individual fibrinogen polypeptide chains in different tissues. Unresolved is the question of applicability of hemostatic corrective drugs in the absence of expressed thrombotic and hemorrhagic manifestations.

THROMBOELASTOMETRY IN THE DIAGNOSIS OF ACUTE COAGULOPATHIES. A CLINICAL CASE OF POISONING WITH WARFARIN

The spread of cardiovascular pathology has brought its directives in the treatment of diseases. Currently, drugs from the groups of antiaggregants and new oral anticoagulants are widely used. Drugs belonging to the group of vitamin K antagonists do not lose their importance in the treatment of cardiological patients. Monitoring the treatment of these patients requires improvement of modern diagnostic technologies. A conventional coagulogram has now been replaced by a more modern method of diagnosing hemostasis disorders – thromboelastometry (TEM). TEM, unlike a standard coagulogram, enables to evaluate all the links of hemostasis in a limited period of time. This article presents a clinical case of poisoning with a drug from the anticoagulants group – warfarin and an example of using thromboelastometry in the diagnosis of this coagulopathy.

Inherited thrombophilia and venous thromboembolism: testing rules in clinical practice

Testing for inherited thrombophilia in patients with venous thromboembolism is one of the most common genetic testing options prescribed by clinicians. Despite the large evidence base for the relationship of hereditary hemostasis disorders with the risk of venous thrombosis, most patients should not be tested. Performing tests in the acute phase of thrombosis or during anticoagulant therapy leads to erroneous results. The choice of anticoagulant therapy regimen and its duration are not specified by the presence of hereditary thrombophilia. The test results can be useful for increasing medication adherence of patient, determining the cause of thrombosis, especially at a young age or in atypical localization.

Novel coronavirus infection COVID-19: extrapulmonary manifestations

The novel coronavirus infection COVID-19 in most cases manifests with respiratory symptoms and fever, however, some patients may have cardiovascular and gastroenterological manifestations. A feature of the clinical syndrome of COVID-19 is the development of pronounced immunopathological reactions and disorders of hemostasis, leading to the development of a wide range of cardiovascular complications. The course of COVID-19 may be complicated by the development of acute myocardial infarction, venous and arterial thrombosis and thromboembolism in various vascular pools, the development of acute myocardial damage and myocarditis. Among the gastroenterological manifestations, diarrhea, nausea or vomiting, as well as abdominal pain, are most often detected. These symptoms may precede the appearance of respiratory signs of the disease, and in some cases come to the fore in the clinical picture of the disease. In addition, in some patients there are laboratory signs of liver injury (increased serum transaminases). The exact pathogenesis of the above disorders continues to be studied.

Catechin and epicatechin as an adjuvant in the therapy of hemostasis disorders induced by snake venoms

Snake toxins, such as phospholipases A2 and proteases, are used as research tools to evaluate biological activities and to understand physiopathological processes of natural compounds better. In the present study, the phenolic compounds catechin and epicatechin were incubated with snake venoms to evaluate their inhibition against different substrates. Catechin and epicatechin exerted inhibitions between 20% and 95% on the activity of phospholipases A2 present in the venom of Bothrops alternatus. In the hemolytic activity, catechin exerted inhibitions between 20% and 25% in all proportions evaluated on the B. jararacussu venom, whereas epicatechin inhibited 20% of the venom activity. Coagulation induced by B. atrox and B. jararacussu venoms was significantly inhibited by catechin and epicatechin, where the time for coagulation was two to three times higher after previous incubation of the venoms with the compounds. The most significant inhibitions for the proteolytic activity on casein were 17% and 27%, respectively, by both compounds. Catechin inhibited serine protease activity induced by B. atrox venom by 64% and epicatechin by 65%. Regarding B. atrox-induced thrombolysis, catechin exerted 40% inhibition and epicatechin around 30%. The fibrinogen proteolysis was completely inhibited by catechin acting on the B. atrox venom in the proportion of 1:1 and by epicatechin on B. jararacussu venom. Catechin and epicatechin showed promising inhibitory action on proteases and phospholipases A2 . Therefore, these compounds can be explored as an adjuvant for serum therapy or pharmaceutical purposes, once they act on homologous enzymes that are present in humans.

Management of hemodialysis facilities and services during the COVID-19 pandemic: Adapted clinical guidelines of the Ukrainian Association of Nephrologists and Kidney Transplant Specialists

The global COVID-19 pandemic is a critical time for hemodialysis patients as hypertension, diabetes or other co-morbidities, as well as hemostasis disorders, are risk factors for adult distress syndrome, the formation of which significantly worsens the prognosis.
 Several national associations of nephrologists have created expert working groups to prepare constantly updated clinical guidelines for the management of dialysis patients in the context of the COVID-19 pandemic.
 According to the experts, to minimize COVID-19 infection of patients and health care workers, the medical staff of dialysis units should undergo training and further retraining, following changes in constantly updated practical recommendations.
 The expert group of the Ukrainian Association of Nephrologists and Kidney Transplant Specialists has also created the Adapted Clinical Guidelines for the Management of Hemodialysis Facilities and Services During the COVID-19 pandemic.
 All of the following clinical guidelines have a level of evidence of 2C.

Advances in Platelet Function Testing-Light Transmission Aggregometry and Beyond.

Platelet function testing is essential for the diagnosis of hemostasis disorders. While there are many methods used to test platelet function for research purposes, standardization is often lacking, limiting their use in clinical practice. Light transmission aggregometry has been the gold standard for over 60 years, with inherent challenges of working with live dynamic cells in specialized laboratories with independent protocols. In recent years, standardization efforts have brought forward fully automated systems that could lead to more widespread use. Additionally, new technical approaches appear promising for the future of specialized hematology laboratories. This review presents developments in platelet function testing for clinical applications.

SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients.In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis.

Features of hemostasis disorders in patients with CKD VD stage and their relationship with the course of the disease

Disorders in the hemostatic system leading to the development of thrombosis are one of the main complications in patients with chronic kidney disease (CKD) of stage VD who are on program hemodialysis. The development of thrombophilic syndrome as a process of intravascular coagulation is characterized by systemic activation of procoagulative mechanisms, which are not always compensated by internal natural anticoagulant systems. The determination of early predictors of possible thrombogenesis in the studied category of patients causes significant difficulties. The goal is to study the features of hemostatic system disorders in patients with CKD VD stage who are on programmed hemodialysis, and to assess their relationship with the characteristics of the course of the disease. In 88 patients with CKD of the VD stage who are on program hemodialysis (52 men and 36 women), the features of hemostasis disorders depending on the clinical characteristics of the patients were studied. The indicators of prethrombosis (soluble fibrin (sF), fibrinogen (Fg), functionally inactive forms of prothrombin (FIFP)), postthrombosis (D-dimer (D-d)) and anticoagulation (protein C (pC)) were determined depending on gender, hemodialysis experience, age, the presence of anemia, arterial hypertension (AH) and preserved residual renal function (RRF). Statistical processing of materials was carried out using methods of variation statistics using t-student criterion. It was found that violations in the hemostatic system are detected in almost all patients. At the same time, hyperfibrinogenemia, an increase in sF concentration, a deficiency of pC, less often an accumulation of FIFP and high levels of D-d are most often observed. These disorders of hemostasis are more often found in patients with absent RRF, a longer experience of hemodialysis, the presence of arterial hypertension and are less associated with gender, age of patients and are little dependent on the degree of anemia.

Anesthésie de la femme enceinte dans le contexte de la pandémie de COVID-19

RésuméLa pandémie de COVID-19 n’a pas épargné les femmes enceintes. Le tableau clinique et biologique est peu spécifique mais la littérature n’a pas retrouvé de susceptibilité accrue des parturientes, à l’infection virale, notamment aux formes graves, ayant comme principale conséquence une prématurité induite et les complications qui en résultent. La pandémie a fait revoir l’organisation de la prise en charge des femmes enceintes, avec une généralisation de la téléconsultation et une réduction d’accès des d’accompagnants en salle de travail comme en suite de couche. La décision du mode d’accouchement est restée uniquement dépendante de l’évaluation obstétricale dans les formes mineures ou asymptomatiques, de même que le mode d’anesthésie à privilégier pour le travail ou la césarienne est resté l’anesthésie locorégionale périmédullaire, en prenant soins de vérifier l’hémostase du fait de l’impact du virus, notamment sur le taux de plaquettes. D’autres situations spécifiques, comme la prise en charge de la fièvre ou de l’hypertension artérielle du péri-partum, n’ont pas été modifiées par le statut viral des parturientes. Le post-partum est la période qui a fait l’objet du plus grand nombre de modifications avec l’administration plus large d’anticoagulants et une utilisation restreinte des AINS. Le point clé de la prise en charge obstétricale en cette période de pandémie a finalement été la coopération interdisciplinaire, impliquant anesthésiste-réanimateur, gynécologue et pédiatres.

Гемостаз у лиц с сахарным диабетом 2‑го типа и ожирением при острой и хронической цереброваскулярной патологии

Введение. В настоящее время цереброваскулярные заболевания (ЦВЗ) в России являются второй по частоте причиной смерти среди больных сахарным диабетом (СД). С гипергликемией и избыточной массой тела связывают протромботические и провоспалительные изменения, приводящие к неблагоприятным исходам инсульта и прогрессированию ЦВЗ. Цель исследования: оценить роль избыточной массы тела как дополнительного фактора риска развития нарушений гемостаза при острых и хронических формах цереброваскулярной патологии у пациентов с СД 2‑го типа (СД‑2). Материалы и методы. В исследование включено 305 пациентов с ишемическими ЦВЗ: группа 1 — 87 больных с ишемическим инсультом (ИИ) и СД‑2; группа 2 — 58 пациентов с ИИ без СД; группа 3 — 80 больных с хроническими ЦВЗ (ХЦВЗ) и СД‑2; группа 4 — 80 пациентов с ХЦВЗ без СД. Выполнены общесоматический и неврологический осмотр, магнитно-резонансная томография головного мозга, инструментальные исследования с расчетом индекса массы тела (ИМТ) и лабораторные исследования с определением гликемии и гликированного гемоглобина (HbA1c), АДФ-индуцированной (АДФ-АТ) и адреналин-индуцированной (Адр-АТ) агрегации тромбоцитов, коагулограммы, включающей содержание фибриногена и Д-димеров, международное нормализованное отношение, активированное частичное тромбопластиновое время, фибринолитическую активность (ФА), индекс фибринолиза, активность плазминогена и уровень тканевого активатора плазминогена (t-РА). Результаты. Наибольших значений глюкоза и HbA1c достигали у пациентов с ИИ и СД‑2. Во всех группах больных с цереброваскулярной патологией СД‑2 сопровождался ожирением и повышенным ИМТ. ЦВЗ (как ИИ, так и хроническая форма) в сочетании с СД‑2 протекали на фоне протромботического состояния крови, связанного с нарушением всех звеньев гемостаза, и проявлялись увеличением АДФ-АТ и Адр-АТ, повышением содержания фибриногена и Д-димеров при одновременном снижении ФА, индекса фибринолиза, активности плазминогена и уровня t-PA. Самые выраженные нарушения наблюдали у пациентов с ИИ и СД‑2, особенно со стороны фибринолиза. Выявлены значимые корреляции между ИМТ и агрегацией тромбоцитов, уровнями фибриногена и Д-димеров, ФА и t-PA. Заключение. У лиц с СД‑2 острые и хронические ЦВЗ сопровождаются ожирением и увеличенным ИМТ, который взаимосвязан с активацией тромбоцитарного и плазменного гемостаза и снижением фибринолиза. Наибольшие изменения отмечены у пациентов с острым инсультом и СД‑2, для которых характерно сочетание гиперфибриногенемии и значительное снижение фибринолиза. Повышение ИМТ у больных ЦВЗ ассоциировано с выраженностью протромботических изменений. Introduction. At present cerebrovascular diseases (CVD) in Russia is the second most common cause of death among patients with diabetes mellitus (DM). Prothrombotic and pro-inflammatory changes leading to adverse outcomes of stroke and progression of CVD are associated with hyperglycemia and obesity. Aim: to assess the role of obesity as an additional risk factor for the development of hemostasis disorders in acute and chronic forms of cerebrovascular pathology in patients with type 2 diabetes mellitus (DM‑2). Materials and methods. The study included 305 patients with ischemic CVD: group 1 — 87 patients with ischemic stroke (IS) and DM‑2; group 2 — 58 patients with IS without DM; group 3 — 80 patients with chronic CVD (CCVD) and DM‑2; group 4 — 80 patients with CCVD without DM. The following studies were completed: somatic and neurological examinations, magnetic resonance imaging of the brain, calculation of body mass index (BMI) and laboratory tests with the determination of glycemia and glycated hemoglobin (HbA1c), ADP-induced (ADP-AT) and adrenaline-induced (Adr-AT) platelet aggregation, coagulogram with fibrinogen and D-dimers content, international normalized ratio, activated partial thromboplastin time, fibrinolytic activity (FA), fibrinolysis index (FI), plasminogen activity and level of tissue plasminogen activator (t-PA). Results. The highest values of glucose and HbA1c were found in patients with IS and DM‑2. In all groups of patients with cerebrovascular pathology DM‑2 was accompanied with obesity and increased BMI. CVD (both IS and chronic form) in combination with DM‑2 were accompanied by prothrombotic blood state (associated with hemostasis disorders), and manifested by enhancement of ADP-AT and Adr-AT, increasing of fibrinogen and D-dimers content and decreasing of FA, FI, plasminogen activity and t-PA. Most expressed disturbances (especially in fibrinolysis) were observed in patients with IS and DM‑2. Significant correlations were found between BMI and platelet aggregation, levels of fibrinogen and D-dimers, FA and t-PA. Conclusion. In patients with DM‑2 acute and chronic CVD are accompanied by obesity and increased BMI and associated with activation of platelet and plasma hemostasis and decreased fibrinolysis. The largest changes were noted in patients with acute stroke and DM‑2 and characterized by a combination of hyperfibrinogenemia and a significantly decreased fibrinolysis. Increasing of BMI in patients with CVD was associated with the severity of prothrombotic changes.

Effects of Four-Week Rehabilitation Program on Hemostasis Disorders in Patients with Spinal Cord Injury.

Background: Patients with spinal cord injury (SCI) exhibit hemostasis disorders. This study aims at assessing the effects of a 4-week rehabilitation program on hemostasis disorders in patients with SCI. Methods: Seventy-eight in-patients undergoing a 4-week rehabilitation were divided into three groups based on time elapsed since SCI: I (3 weeks–3 months), II (3–6 months), and III (>6 months). Tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin–antithrombin complex (TAT) and D-dimer levels, antithrombin activity (AT), and platelet count (PLT) were measured on admission and after rehabilitation. Results: Rehabilitation resulted in an increase in TF in group III (p < 0.050), and decrease in TFPI (p < 0.022) and PLT (p < 0.042) in group II as well as AT in group I (p < 0.009). Compared to control group without SCI, TF, TFPI, and TAT were significantly higher in all SCI groups both before and after rehabilitation. All SCI groups had elevated D-dimer, which decreased after rehabilitation in the whole study group (p < 0.001) and group I (p < 0.001). Conclusion: No decrease in activation of TF-dependent coagulation was observed after a 4-week rehabilitation regardless of time elapsed since SCI. However, D-dimer levels decreased significantly, which may indicate reduction of high fibrinolytic potential, especially when rehabilitation was done <3 months after SCI.

Thrombotic microangiopathy in rheumatology: a link between thrombosis and autoimmunity

Uncontrolled hypercoagulation and inflammation (thromboinflammation), which are both independent and closely related and amplifying each other pathological processes, form the basis for pathogenesis of a wide range of diseases and complications, including immuno-inflammatory (autoimmune) rheumatic diseases, with the development of potentially fatal injuries of internal organs. Thrombotic microangiopathy is one of the most prominent prototypes of thromboinflammatory pathological conditions. The close link between environmental factors, hemostasis genetic defects and the complement system, inflammation and autoimmunity as pathogenetic mechanisms of microthrombosis draws particular attention to studying thrombotic microangiopathy in immuno-inflammatory rheumatic diseases, primarily systemic lupus erythematosus, antiphospholipid syndrome and scleroderma renal crisis. In future, these studies may be important for expanding the idea of the role of autoimmune mechanisms in pathogenesis of critical hemostasis disorders in human diseases, and for developing new approaches to therapy. Recently, special attention has been paid to the treatment of systemic lupus erythematosus and antiphospholipid syndrome with eculizumab, which is humanized monoclonal IgG2/4k antibody that blocks the complement component C5a and the membrane attack complex (C5b-9) formation, and which is registered for the treatment of atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, as well as severe forms of myasthenia gravis and neuromyelitis optica. Further studies in this direction will create prerequisites for improving the prognosis not only in patients with orphan disorders, but also for widespread human diseases.