Prevention of massive intraoperative bleedings associated with heparin with the systemic use of fibrin monomer in the experiment

2019 ◽  
pp. 48-55
Author(s):  
А.П. Момот ◽  
В.М. Вдовин ◽  
Д.А. Орехов ◽  
Н.А. Лычёва ◽  
И.Г. Толстокоров ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Unfractionated Heparin ◽  
Loss Rate ◽  
Antithrombin Iii ◽  
Fibrinogen Level ◽  
Circulating Blood Volume ◽  
Intraoperative Bleeding ◽  
Fibrin Monomer ◽  
Antithrombin Iii Activity

Цель исследования - изучение способности фибрин-мономера предупреждать тяжелую интраоперационную кровопотерю, ассоциированную с введением нефракционированного гепарина, при дозированной травме печени. Методика. На кроликах «Шиншилла» индуцировали гипокоагуляцию нефракционированным гепарином (150 ед/кг). Профилактику интраоперационных кровотечений осуществляли внутривенным введением фибрин-мономера (0,25 мг/кг) за 1 ч до травмы или протамина сульфата (1,5 мг/кг) за 10 мин до травмы. После нанесения стандартной травмы печени оценивали объем (в % ОЦК) и темп (мг/с) кровопотери. Анализировали число тромбоцитов, активированное парциальное тромбопластиновое время, протромбиновое и тромбиновое время свертывания, уровень фибриногена и активность антитромбина III, параметры ротационной тромбоэластометрии крови. Результаты. Объем кровопотери в группах животных после в/в введения фибрин-мономера и протамина сульфата на фоне гепаринизации был, соответственно, в 5,1 и 4,0 раза меньше по сравнению с группой плацебо, получавшей тот же антикоагулянт. Вместе с тем, фибрин-мономер не влиял на параметры коагулограммы (отсутствие видимого гемостазиологического эффекта) и тромбоэластограммы, тогда как применение протамина сульфата в качестве антидота гепарина сопровождалось нормализацией данных тромбоэластометрии и коррекцией гипокоагуляционного сдвига по активированному парциальному тромбопластиновому времени, протромбиновому и тромбиновому времени. Заключение. Установлено, что фибрин-мономер (0,25 мг/кг) снижает посттравматическое кровотечение в условиях блокады свертывания крови гепарином без видимых признаков восстановления гемостатического равновесия. The research objective was to study the ability of fibrin monomer to prevent severe intraoperative blood loss associated with administration of unfractionated heparin in controlled liver injury. Methods. Hypocoagulation was induced in chinchilla rabbits with unfractionated heparin (150 U/kg). Intraoperative bleeding was prevented by administration of fibrin monomer (FM, 0.25 mg/kg, i.v.) one hour prior to the injury and of protamine sulfate (PS, 1.5 mg/kg, i.v.) 10 min prior to the injury. Following the liver injury, blood loss was assessed as percentage of circulating blood volume and the blood loss rate (mg/s). Platelet counts, aPTT, PT, TT, fibrinogen level, antithrombin III activity, and parameters of blood rotation thromboelastometry were analyzed. Results. The volume of blood loss was 5.1 times and 4.0 times less, respectively, after the FM and PS administration during heparinization compared to the placebo group treated with the same anticoagulant. However, FM affected neither coagulogram indexes (no visible hemostasiological effect) nor thromboelastogram while the use of PS as an antidote for heparin was associated with normalization of thromboelastometric data and correction of hypercoagulative changes in aPTT, PT, TT. Conclusion. FM at a dose of 0.25 mg/kg reduced severity of posttraumatic bleeding induced by heparin inhibition of coagulation with no visible signs of hemostatic balance recovery.

scholarly journals Effect of an exogenous fibrin monomer on hemostatic potential and fibrin formation in the area of controlled liver injury on the background of heparin administration in experiment

2020 ◽  
pp. 32-42
Author(s):  
А.П. Момот ◽  
В.М. Вдовин ◽  
Д.А. Орехов ◽  
И.П. Бобров ◽  
И.И. Шахматов ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Morphological Study ◽  
Fibrillar Structure ◽  
Fibrinogen Concentration ◽  
Wound Surface ◽  
Circulating Blood Volume ◽  
Hemostatic Effect ◽  
Fibrin Formation ◽  
Fibrin Monomer

Актуальность. В проведенных ранее исследованиях на «гепариновой» модели посттравматической кровопотери был продемонстрирован гемостатический эффект экзогенно вводимого фибрин-мономера (ФМ) (доза 0,25 мг/кг), сопоставимый по выраженности с применением протамина сульфата (ПС), что не получило своего объяснения из-за отсутствия данных морфологического исследования в зоне травмы печени. Цель. Сопоставить гемостатические, гемостазиологические и морфологические последствия использования ФМ, при его внутривенном введении в дозе 0,25 мг/кг, у гепаринизированных животных, после дозированной травмы печени. Материалы и методы. На 77 здоровых кроликах породы «Шиншилла» моделировали гипокоагуляцию нефракционированным гепарином (НГ) в/в в дозе 150 ед/кг. Профилактику интраоперационных кровотечений осуществляли введением ФМ в/в в дозе 0,25 мг/кг, за один час до травмы, и ПС в/в в дозе 1,5 мг/кг за 10 мин до травмы. После нанесения дозированной травмы печени кровопотерю оценивали в % от объема циркулирующей крови. Исследовали также содержание тромбоцитов в крови, активированное парциальное тромбопластиновое время (АПТВ), уровень фибриногена и количество D-димера, параметры калиброванной тромбографии. Ткани печени в области раневой поверхности для гистологических исследований получали после спонтанной остановки кровотечения. Результаты. Гепаринизированным животным была свойственна повышенная кровопотеря на фоне выраженной гипокоагуляции и снижении генерации тромбина. Применение антидота НГ - ПС, минимизировало потерю крови (снижение кровопотери в 4,0 раза по сравнению с плацебо) и приводило к восстановлению гемостатического потенциала. Согласно морфологическим исследованиям, это достигалось увеличением толщины тромботических масс (в 15,1 раза по сравнению с плацебо). В не меньшей степени гемостатический эффект был достигнут при замене ПС на ФМ (уменьшение кровопотери в 5,1 раза по сравнению с плацебо). Данные эффекты не сопровождались коррекцией гипокоагуляционного сдвига и восстановлением генерации тромбина. В последнем случае определено меньшее по выраженности фибринообразование в зоне травмы (толщина фибрина 55,2 мкм против 201,8 мкм при применении ПС; р < 0,001). Еще одной отличительной особенностью явилось отсутствие фибриллярной структуры фибрина и наличие в тромботических массах многочисленных тромбоцитов, тогда как их число в просветах сосудов рядом с раневой поверхностью было минимальным. Заключение. Приведенные данные позволяют обозначить возможные механизмы и пути остановки постравматического кровотечения при использовании гепарина. Background. In previous studies using the heparin model of post-traumatic blood loss, a hemostatic effect of exogenous fibrin monomer (FM) (0.25 mg/kg) was observed, which was comparable in intensity to the effect of protamine sulfate (PS) and remained unexplained due to the lack of morphological study data for the area of liver injury. Aim. To compare hemostatic, hemostasiological, and morphological consequences of intravenous administration of FM 0.25 mg/kg following controlled liver injury in heparinized animals. Methods. Hypocoagulation was simulated by i.v. administration of unfractionated heparin (UFH) 150 U/kg to 77 healthy Chinchilla rabbits. Intraoperative bleeding was prevented by i.v. administration of FM 0.25 mg/kg one hour prior to the injury or PS 1.5 mg/kg 10 minutes prior to the injury. After the controlled liver injury, blood loss was measured and expressed in % of the circulating blood volume. Blood platelet count, activated partial thromboplastin time (APTT), fibrinogen concentration, D-dimer concentration, and data of calibrated thrombography were also studied. Samples of liver tissue from the wound surface area were collected for histology after spontaneous arrest of bleeding. Results. Heparinized animals were characterized by increased blood loss due to pronounced hypocoagulation and decreased thrombin production. The use of the UFH antidote, PS, minimized the blood loss (by 75% compared to placebo) and resulted in restoration of the hemostatic potential. According to results of the morphological study, this effect was due to increased thickness of thrombotic masses (15.1 times compared to placebo). At least equal hemostatic effect was obtained when PS was replaced with FM (80% decrease in blood loss compared to placebo). These effects were not associated with correction of the hypocoagulation shift or recovery of the thrombin generation. In this process, fibrin formation in the injury area was less pronounced (fibrin thickness 55.2 µm vs 201.8 µm with PS; p < 0.001). Another distinctive feature was the absence of the fibrillar structure of fibrin and the presence of numerous platelets in thrombotic masses while the platelet number in the lumen of blood vessels near the wound surface was minimal.

Systemic hemostatic and hemostasiological effects of fibrin monomer in low dose under warfarin action in experiment

2019 ◽  
Author(s):  
В.М. Вдовин ◽  
А.П. Момот ◽  
Д.А. Орехов ◽  
И.Г. Толстокоров ◽  
В.О. Шевченко ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Prothrombin Complex Concentrate ◽  
Coagulation Factors ◽  
International Normalized Ratio ◽  
Blood Coagulation Factors ◽  
Circulating Blood Volume ◽  
Hemostatic Effect ◽  
Blood Loss Volume

Введение. Ранее было показано, что фибринмономер (ФМ) в низких дозировках обладает системным гемостатическим действием в условиях дозированной травмы. Авторами выдвинута гипотеза, согласно которой ФМ способен оказывать регулирующее гемостатическое действие in vivo на фоне сниженного гемостатического потенциала. Цель исследования: изучение системных гемостатических и гемостазиологических эффектов ФМ на фоне дозированной травмы печени при гипокоагуляции, обусловленной приемом варфарина. Материалы и методы. В работе использовали 40 кроликов породы Шиншилла. Для индукции кумаринобусловленной гипокоагуляции животным per os вводили варфарин в дозе 0,4 0,5 мг/кг 14 дней до достижения международного нормализованного отношения (МНО) более 2,0. Далее животным в краевую вену уха вводили концентрат факторов протромбино вого комплекса (КФПК) в дозе 40 ЕД/кг, ФМ в дозе 0,25 мг/кг или плацебо. Через 1 ч после введения препаратов наносили травму печени и оценивали кровопотерю (в процентах от объема циркулирующей крови). Исследовали число тромбоцитов, активированное парциальное тромбопластиновое время, МНО, содержание фибриногена и Ддимера, оценивали результаты тромбоэластографии крови. Результаты. Объем кровопотери в группах животных после внутривенного введения ФМ и КФПК на фоне приема варфарина был в 9,1 раза и 6,7 раза меньше, соответственно, по сравнению с группой плацебо, получавшей тот же антикоагулянт. Вместе с тем ФМ не влиял на параметры коагулограммы (отсутствие видимого гемостазиологического эффекта) и тромбоэластограммы, тогда как применение КФПК в качестве антидота варфарина сопровождалось нормализацией параметров тромбоэластометрии и коррекцией гипокоагуляционного сдвига по МНО. Заключение. Установлено, что ФМ способен проявлять свое системное гемостатическое действие в условиях сниженного тромбинообразования, обусловленного нарушением синтеза витамин Кзависимых факторов свертывания крови. Данное действие реализуется без признаков восстановления гемостатического равновесия. Introduction. It was shown earlier that fibrinmonomer (FM) in low doses had a systemic hemostatic effect in a controlled injury condition. The authors suggest that FM is able to exert a regulating hemostatic effect in vivo under reduced hemostatic potential. Aim: to study the systemic hemostatic and hemostasiological effects of FM under controlled liver injury during hypocoagulation caused by warfarin administration. Materials and methods. In this study 40 Chinchilla rabbits were used. For the induction of coumarinmediated hypocoagulation, animals were administered per os warfarin at a dose of 0.4 0.5 mg/kg for 14 days, until an international normalized ratio (INR) was more than 2.0. Subsequently, a prothrombin complex concentrate (PCC) at a dose of 40 U/kg, FM at a dose of 0.25 mg/kg or placebo were administered into the marginal ear vein of the animals. An hour later, a liver injury was inflicted and blood loss was assessed (in percents of the circulating blood volume). The number of platelets, activated partial thromboplastin time, INR, levels of fibrinogen and Ddimer were studied and the results of blood thromboelastography were evaluated. Results. Blood loss volume in animals groups after intravenous administration of FM and PPC, under warfarin reception, was 9.1 times and 6.7 times less, respectively, compared to the placebo group receiving the same anticoagulant. However, FM did not affect on coagulogram parameters (no visible hemostasiological effect) and thromboelastogram, whereas the use of PPC as warfarin antidote was accompanied by the normalization of thromboelastometry parameters and hypocoagulation shift correction according to INR. Conclusion. It was found that FM able to manifest its systemic hemostatic effect in conditions of reduced thrombin formation caused by impaired synthesis of vitamin Kdependent blood coagulation factors. This effect is implemented without any signs of recovery of hemostatic balance.

scholarly journals Assessment of the effect of exogenous fibrin monomer on post-traumatic bleeding in hypofibrinogenemia caused by administration of snake venom Agkistrodon rhodostoma

2020 ◽  
Vol 101 (5) ◽  
pp. 704-712
Author(s):  
V M Vdovin ◽  
A P Momot ◽  
D A Orekhov ◽  
I I Shakhmatov ◽  
N A Lycheva ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Snake Venom ◽  
Disseminated Intravascular Coagulation ◽  
Intravascular Coagulation ◽  
Hemostatic Effect ◽  
Fibrin Monomer ◽  
Traumatic Bleeding ◽  
Post Traumatic ◽  
D Dimer

Aim. To assess the effect of fibrin monomer on the rate of blood loss after controlled liver injury in hypofibrinogenemia induced by systemic administration of Malayan pit viper venom (Agkistrodon rhodostoma). Methods. A placebo-controlled study of the hemostatic effect of fibrin monomer administered intravenously at 0.25 mg/kg, and coagulation parameters in the controlled liver injury with profound hypofibrinogenemia caused by administration of Malayan pit viper venom was conducted in 34 male Chinchilla rabbits. The distribution of the studied parameters was investigated by the ShapiroWilk test. Statistical differences between groups were tested by Students t-test, MannWhitney U test, or Wilcoxon test, as appropriate. Differences in mortality rate were examined using Fisher's exact test. Results. A model of experimental toxogenic disseminated intravascular coagulation was reproduced, manifested by high mortality of animals (50.0%), severe blood loss (increased blood loss by 1.78 times), hemolysis, a decreased platelet count (by 19.6% of median) and platelet dysfunction, fibrinogen consumption (protein content less than 0.9 g/l), hypocoagulation as well as intensive D-dimer production (increased concentration by 25.0 times of median). A high level of the fibrin derivative demonstrated activation of fibrin formation and fibrinolysis in the bloodstream of the animals. Systemic prophylactic administration of exogenous fibrin monomer after receiving snake venom did not lead to a decrease in post-traumatic bleeding, whereas earlier, during reproduction of disseminated intravascular coagulation caused by streptokinase infusion, such a hemostatic effect of fibrin monomer was shown. Conclusion. The absence of fibrin monomer effect (at a dose of 0.25 mg/kg) on the severity of blood loss in toxogenic disseminated intravascular coagulation may be associated with more profound disseminated intravascular coagulation and a sharp 25-fold increase in D-dimer levels that can act as a fibrin monomer polymerization inhibitor.

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

2021 ◽  
Author(s):  
Д.И. Поздняков ◽  
В.М. Руковицина ◽  
А.В. Сосновская ◽  
Е.А. Олохова
Keyword(s):  
Platelet Aggregation ◽  
Antithrombin Iii ◽  
Serum Levels ◽  
Thrombin Time ◽  
Cytokine Storm ◽  
Reference Drug ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Antithrombin Iii Activity ◽  
D Dimer

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.

Thrombin, Fibrin Monomer and Factor XIII in Patients with Unexplained Intraoperative Bleeding.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4025-4025
Author(s):  
Wolfgang C. Korte ◽  
Konrad Gabi ◽  
Anita Gähler ◽  
Thomas Schnider ◽  
Walter Riesen
Keyword(s):  
Blood Loss ◽  
Factor Xiii ◽  
Elective Surgery ◽  
Monomer Concentration ◽  
Coagulation Cascade ◽  
Intraoperative Blood Loss ◽  
Double Blind ◽  
Intraoperative Bleeding ◽  
Fibrin Monomer ◽  
Preoperative Risk Stratification

Abstract To explore relevant changes in unexplained intraoperative bleeding, we evaluated elements of the final steps of the coagulation cascade in 226 consecutive patients undergoing elective surgery. Patients were stratified for the occurrence of unexplained intraoperative bleeding according to predefined criteria. Twenty patients (8.8%) developed unexplained bleeding. Median intraoperative blood loss was 1350 ml (bleeders) and 400 ml (non-bleeders), p<0.001. Fibrinogen and factor XIII were more rapidly consumed in bleeders (p<0.001). Soluble fibrin formation (fibrin monomer) was elevated in bleeders throughout surgery (p < 0.014, table 1). However, F. XIII availability per unit thrombin generated was significantly decreased in bleeders pre-, intra- and postoperatively (p < 0.051). Computerized thrombelastography showed a parallel, significant reduction in clot firmness. We suggest that a mild, pre-existing coagulopathy is not rare in surgical patients and probably can result in clinically relevant intraoperative bleeding. This haemostatic disorder shows impaired clot firmness, probably secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute measures and per unit thrombin generated). We are currently conducting a double blind, randomized trial on the use of F. XIII early during surgery. We suggest that the preoperative measurement of fibrin monomer concentration might allow preoperative risk stratification for intraoperative blood loss. Fibrin Monomer is increased in “bleeders” Non-Bleeder (FM median μg/l) Bleeder (FM median μg/l) p (Rank Sum test) T1 (preop) 7 18 <0.01 T2 (intraop) 6 14 <0.01 T3 (intraop) 9 20 0.014 T4 (postop) 26 52 <0.01 T5 (postop) 29 86 <0.01

scholarly journals Hemostatic system parameters and level of magnesium in patients with beta-thalassemiа

2020 ◽  
Vol 101 (2) ◽  
pp. 188-192
Author(s):  
N R Aliyeva
Keyword(s):  
Antithrombin Iii ◽  
Fibrinogen Level ◽  
Serum Magnesium ◽  
Beta Thalassemia ◽  
Control Group ◽  
System Parameters ◽  
Hemostatic System ◽  
Thalassemia Minor ◽  
Antithrombin Iii Activity ◽  
D Dimer

Aim. To study the hemostatic system parameters and magnesium levels in patients with beta-thalassemia. Methods. The object of the study was the blood serum of 96 women with beta-thalassemia: 46 patients with intermediate beta-thalassemia and 50 patients with beta-thalassemia minor, without clinical manifestations of hypercoagulation. The blood serum of 30 healthy donors was used as the control group. It was studied hemostasis system parameters: platelet count activated partial thromboplastin time (aPTT), prothrombin time, plasma fibrinogen level, D-dimer level, euglobulin clot lysis time, antithrombin III activity. The serum magnesium level and risk of deficiency were determined using the MDQ questionnaire. Results. In patients with intermediate beta-thalassemia, an increase in the level of thrombinemia marker D-dimer (500 ng/ml) was revealed. Patients with intermediate beta-thalassemia were divided into two groups according to the revealed level of D-dimer: 14 (30.46.8%) patients with latent hypercoagulation in group 1 and 32 (69.66.8%) patients without latent hypercoagulation in group 2. It was found that in the group with a high levels D-dimer, fibrinogen level was increased (p 0.05), fibrinolysis time was prolonged (p 0.05), activated partial thromboplastin time was shortened (p 0.05), and antithrombin III activity was slightly reduced (p 0.05). The serum magnesium level in patients of the first group was lower (t=7.3; p 0.001), and the risk of deficiency in the questionnaire was higher than in patients of the second group (r=0.785, p 0.05). Hemostasis and magnesium levels in patients with beta-thalassemia minor did not differ from the control group (p 0.05). Conclusion. One-third of patients with intermediate beta-thalassemia have a pre-thrombotic state for hemostasis latent hypercoagulation and magnesium deficiency which can be predictors of clinical signs of thrombosis.

scholarly journals Features of adjusting the aggregate state of women’s blood with dysfunctional bleeding in reproductive age

2014 ◽  
Vol 18 (2 (70)) ◽  
Author(s):  
I. V. Byrchak
Keyword(s):  
Blood Serum ◽  
Activity Concentration ◽  
Antithrombin Iii ◽  
Fibrinogen Level ◽  
Reproductive Age ◽  
Dysfunctional Uterine Bleeding ◽  
Aggregate State ◽  
Potential Activity ◽  
Antithrombin Iii Activity ◽  
Fibrinolytic Potential

The general coagulation blood potential, fibrinolytic activity of plasma, antiplasmin and plasmin potential activity, fibrinogen level in blood serum, antithrombin III activity, concentration of soluble fibrin-monomer complexes in the blood serum were estimated in women with anaemia of I degree on a background of the dysfunctional uterine bleeding. The changes of blood fibrinolytic potential have secondary nature, that is conditioned by activating the trombinogenesis and fibrinogenesis externally. The hypercoagulation develops by activating the hemopexis through the external mechanism of protrombinasa formation, which is accompanied by a decrease of anticoagulation potential and an increase of aggregation features of thrombocytes.

scholarly journals 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

2021 ◽  
Vol 102 (5) ◽  
pp. 642-653
Author(s):  
V M Vdovin ◽  
A P Momot ◽  
I I Shakhmatov ◽  
I P Bobrov ◽  
D A Orekhov ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Liver Injury ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Morphological Features ◽  
Fibrinogen Concentration ◽  
Fibrin Monomer ◽  
Significant Difference ◽  
Induced Aggregation ◽  
Injury Area

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.

scholarly journals Time-dependent systemic hemostatic effects of fibrin monomer in controlled liver injury in the experiment

2019 ◽  
Vol 100 (2) ◽  
pp. 257-263 ◽  
Author(s):  
V M Vdovin ◽  
A P Momot ◽  
D A Orekhov ◽  
I G Tolstokorov ◽  
V O Shevchenko ◽  
...  
Keyword(s):  
Liver Injury ◽  
Controlled Study ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Circulating Blood Volume ◽  
Optimal Interval ◽  
Hemostatic Effect ◽  
Fibrin Monomer ◽  
Injury Model ◽  
Time Periods

Aim. To evaluate the hemostatic effect of fibrin monomer after its intravenous administration at different time periods in experimental trauma. Methods. In the experiments, in a placebo-controlled study, hemostatic and hemostasiological effects of systemic use of fibrin monomer were studied at different time periods after its administration (in 5 min, 1 h and 3 h) in 97 male rabbits of the Chinchilla breed in the controlled liver injury model. Results. A pronounced hemostatic effect was demonstrated for fibrin monomer used at a dose of 0.25 mg/kg demonstrated by a 6.3-fold decrease of blood loss volume (% of circulating blood volume) compared to placebo on the background of the intravenous preventive fibrin monomer administration 1 hour prior to controlled liver injury. Fibrin monomer administration at a stated dose was not accompanied by significant changes in haemocoagulative parameters including measurement of platelet count, activated partial thromboplastin time, prothrombin time, thrombin time, echitox time, fibrinogen concentration, level of soluble fibrin monomer complexes, D-dimer content, and antithrombin III activity. The effect of fibrin monomer is probably realized through some effectors, the nature of which has not yet been studied. The obtained results allow choosing the optimal interval between intravenous administrations of fibrin monomer and controlled liver injury for further study of the mechanisms of its hemostatic action. Conclusion. Fibrin monomer in small doses (0.25 mg/kg) is able to exert a pronounced hemostatic effect with its systemic administration 1 hour prior to the injury without significant changes in haemocoagulative parameters.

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