Fibrin Monomer in Chronic HCV ‎Cirrhotic Patients

Background: Cirrhosis is a diffuse pathophysiological state of the liver that is thought to be the final stage of various liver injuries. It is characterized by chronic necroinflammatory and fibrogenetic processes, which result in the conversion of normal liver architecture into structurally abnormal nodules, dense fibrotic septa, concomitant parenchymal exaustment, and liver tissue collapse. Aim of this Work is to study fibrin monomer in chronic HCV patients with and without portal hypertension aiming to investigate its value in these patients and if it aides in early detection of thrombus formation.‎ Patients and Methods: They were fifty chronic HCV cirrhotic patients with and ‎without portal hypertension. Patients of these study were selected from Tropical and internal medicine departments and investigated at Clinical Pathology department in Tanta University hospitals, Faculty of Medicine, Tanta University during the period from July 2018 to January 2020. Results: The individuals included in this study were comprised as: Group 1: Twenty-five healthy volunteers (matched for age and gender) were investigated as a control group. Group 2: Twenty-five diagnosed cirrhotic patients without portal hypertension. Group 3: Twenty-five diagnosed cirrhotic patients with portal hypertension. The result of the present study was statistically analyzed, summarized and presented in tables. Conclusion: It may be concluded that soluble fibrin monomer complex could represent a useful marker ‎for early detection of thrombus generation in chronic HCV cirrhotic patients. It may enable ‎us to pick up vulnerable patients in early stages to start early management.

Effects of tranexamic acid and exogenous fibrin monomer on the liver injury area and systemic circulation in pharmacological suppression of platelet function in an experiment

Aim. To identify and compare the morphological, hemostatic and hemostasiological consequences of intravenous administration of tranexamic acid and fibrin monomer in controlled liver injury against drug-induced thrombocytopathy. Methods. The morphological features of fibrin formation in the area of liver injury after spontaneous bleeding arrest combined with the indicators of blood loss in the animals treated with intravenous placebo, tranexamic acid or fibrin monomer was studied in 69 male rabbits. The effects of these drugs were assessed against thrombocytopathy associated with the combined use of acetylsalicylic acid and clopidogrel. Platelet number and function (adnosine diphosphate-induced aggregation), the data of thromboelastometry and calibrated automated thrombogram, fibrinogen concentration and D-dimer level were considered in the blood test. The feature distribution in the samples was assessed using the ShapiroWilk test. Depending on the distribution, Student's t-test, MannWhitney U test or Wilcoxon signed-rank test were used to test for a significant difference between the features. Differences in mortality rate were established by using Fisher's exact test. The differences were considered statistically significant at p 0.05. Results. A model of thrombocytopathy which showed decreased platelet aggregation function (by 4.5 times), increased blood loss (by 40%), and high mortality (53.9%) was reproduced. Only a small accumulation of thrombotic material was noted on the injured surface of such animals. The use of tranexamic acid led to decreased post-traumatic bleeding (2.5 times) and animal mortality (20%). The latter was provided on the wound surface by increasing the thickness of both thrombotic deposits and fibrin strands. When fibrin monomer was used, the phenomenon of an overcompensated decrease in blood loss (by 6.7 times) accompanied by zero mortality was noted despite a pronounced decrease in platelet aggregation. The maximum increase in the thickness of thrombotic material and fibrin strands was morphologically determined in the injury area compared with other animal groups. Conclusion. Morphological features of traumatic hemostatic effect at the injured area when using tranexamic acid and fibrin monomer have a number of differences despite the similarity of the achieved results in minimizing blood loss.

THROMBOELASTOGRAPHY IN ASSESSING THE HEMOSTATIC SYSTEM IN INTENSIVE CARE PATIENTS

The results of thromboelastography and standard coagulogram were analyzed in 35 patients aged from 18 to 86 who were treated in the resuscitation and intensive care unit. The majority of patients (34%) were hospitalized in the department with multisystem and concomitant injuries. The remaining patients were taken to the medical institution with different diagnoses (urolithiasis, liver cirrhosis, pancreatic lesion of various types, poisoning, peptic ulcer, sepsis). The data of coagulogram and thromboelastography at different stages of treatment were compared. In patients with the development of traumatic shock, the coagulogram parameters were changed to varying degrees depending on the stage of shock. At the first stage of shock, only an increase in soluble fibrin-monomer complexes by almost 2 times and a slight increase in fibrinogen dynamics were noted in the analysis. In a patient with stage 3 traumatic shock, the coagulogram parameters were within the normal range, but according to thromboelastography (EXTEM and FIBTEM tests), hypocoagulation due to the platelet link was noted. Only the coagulogram was evaluated in dynamics, hypocoagulation was noted in the indicators of internal and external hemostasis pathways: lengthening of the activated partial thromboplastin time, a decrease in the prothrombin index and an increase in the international normalized ratio, an increase in fibrinogen A and soluble fibrin-monomer complexes. In the group of male patients with closed craniocerebral trauma, an increase in soluble fibrin-monomer complexes in the coagulogram was always combined with changes in the FIBTEM test during thromboelastography. In most patients, no changes in the classical coagulogram tests immediately after the injury are noted. At this, thromboelastography makes it possible to make up for this deficiency at an earlier time, which indicates a high sensitivity of the method.

Hemostasis system in elderly patients with ischemic insult in the system of carotid arteries

There was performed investigation of rhelogic properties, of coagulation and anticoagulation blood systems in 88 patients of senile age with ischemic insult in the carotid system. It was determined that for elderly patients highly expressed tendencies for hyperaggregation and suppression of their own fibrinolytic blood activity are characteristic features. Initially increased level of aggregation and hypercoagulation, combined with presence in blood fibrin-monomer complexes were accompanied by progressing DIC syndrome, and as a rule, were associated with steady neurology deficiency and high incidence of mortality. Possible correction ways were considered for hemostasis system disorders in elderly patients.

Effect of new chalcone analogues on hemostasis in animals with experimental «сytokine storm»

Введение. «Цитокиновый шторм» представляет собой расстройство иммунной системы с выраженной гиперцитокинемией, характеризующееся развитием коагуляционных нарушений с высоким уровнем летальности. Цель исследования: оценить влияние новых аналогов халкона на изменение реакций гемостаза у крыс в условиях экспериментального «цитокинового шторма». Материалы и методы. Исследование было выполнено на 80 крысах- самцах линии Wistar, разделенных на 8 равных групп по 10 особей. «Цитокиновый шторм» моделировали путем внутрибрюшинного введения липополисахарида в дозе 10 мг/кг. Исследуемые соединения в дозе 20 мг/кг интраперитонеально и препарат сравнения — гепарин (20 ЕД/кг, подкожно) вводили через 60 мин после моделирования патологии. Через 24 ч в сыворотке крови у крыс оценивали содержание фибриногена, D-димера, растворимых фибрин-мономерных комплексов (РФМК), активность антитромбина III (АТ-III), тромбиновое время (ТВ) и степень АДФ-стимулированной агрегации тромбоцитов. Результаты. Применение аналогов халкона способствовало восстановлению гемостатических реакций, что выражалось в снижении концентраций фибриногена, D-димера, РФМК, степени агрегации тромбоцитов и повышении активности АТ-III и ТВ. При этом в ряду изучаемых веществ соединение, содержащее гидроксил во 2-м положении и метильную группу в 5-м положении, проявляло несколько больший уровень фармакологической активности, нежели остальные исследуемые соединения. Заключение. На основании полученных данных можно предположить актуальность дальнейшего изучения аналогов халкона как средств, нормализующих гемостаз при гиперцитокиновых расстройствах. Background. «Cytokine storm» is a disorder of the immune system with severe hypecytokinemia, characterized by the development of coagulation disorders with a high level of mortality. Objectives: to evaluate the effect of new chalcone analogues on changes of hemostasis reactions in rats under the conditions of an experimental «cytokine storm». Materials/Methods. The study was performed on 80 male Wistar rats divided into 8 equal groups of 10 individuals. The «cytokine storm» was modeled in animals by intraperitoneal injection of lipopolysaccharide at a dose of 10 mg/kg. The test-compounds at a dose of 20 mg/kg intraperitoneally and the reference drug — heparin (20 U/kg, subcutaneously) were administered 60 minutes after the pathology simulation. After 24 hours, the serum levels of fi brinogen, D-dimer, soluble fibrin-monomer complexes, antithrombin III activity, thrombin time, and the degree of ADP-stimulated platelet aggregation were evaluated in rats. Results. The study showed that the use of chalcone analogues contributed to the restoration of hemostasis reactions, which was expressed in a decrease in theconcentration of fibrinogen, D-dimer, soluble fibrin-monomer complexes, the degree of platelet aggregation, and an increase in antithrombin III activity and thrombin time. At the same time, among the studied substances, the compound containing hydroxyl in the 2nd position and the methyl group in the 5th position showed a slightly higher level of pharmacological activity than the other test compounds. Conclusions. Based on the obtained data, it is actuality to assume the relevance of further study of chalcone analogues as agents that normalize hemostasis in hypercytokine disorders.