Abstract

Introduction. Earlier studies of low-dose fibrin monomer (FM) demonstrated that low-dose FM has unique hemostatic properties in vivo.Aim — to compare the morphological consequences of intravenous administration of tranexamic acid (TXA) and FM with the hemostatic and hemostasiological effects in hypofibrinogenemia caused by the use of streptokinase after controlled liver injury.Materials and methods. The morphological pattern of fibrin formation in the liver injury area after spontaneous arrest of bleeding in the animals treated with streptokinase or placebo was studied in 73 male rabbits of the Chinchilla breed, split into four groups. In three groups, the study was performed under the conditions of intravenous administration of placebo, TXA, or FM against the background of fibrinolysis activation by streptokinase. Platelet count in the blood, the concentration of fibrinogen, as well as the results of calibrated thrombography, were taken into account.Results. Sequential administration of streptokinase and TXA was accompanied by decreased fibrinogen concentration (by 29.6 %) and, at the same time, a reduction in blood loss (by 15.4 times) in comparison with animals where placebo was used instead of TXA. A decrease in blood loss was associated with increased thickness of thrombotic deposits at the edge of the wound, mainly consisting of red blood cells. These observations were combined with data on the acceleration of thrombin formation in venous blood plasma in a calibrated thrombography test (Peak thrombin 65.4 nmol/L to 109.6 nmol/L in the placebo group). Compared to the observations where placebo was administered instead of FM, however, the sequential use of streptokinase and FM also led to a decrease in blood loss (by 11.0 times) despite decreased fibrinogen concentration (by 23.3 %). A decrease in blood loss was also associated with platelet consumption in venous blood and with increased thickness of thrombotic deposits on the injury surface, where, in addition to red blood cells, the accumulation of fibrin masses was determined by the morphological pattern.Conclusion. The mechanisms of the systemic hemostatic effect of TXA and FM are different, despite the similarity of the achieved hemostatic effects in the conditions of stimulation of blood fibrinolytic activity. These findings expand the understanding of new therapeutic possibilities for reducing post-traumatic blood loss.

Highlights

  • Earlier studies of low-dose fibrin monomer (FM) demonstrated that low-dose FM has unique hemostatic properties in vivo

  • hemostasiological effects in hypofibrinogenemia caused by the use of streptokinase

  • in the animals treated with streptokinase or placebo was studied in

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Summary

Материалы и методы

Исследование выполнено на 73 здоровых кроликахсамцах породы шиншилла массой 3,0–4,5 кг, содержавшихся в стандартных условиях вивария. Животным 1-й группы (n = 21) в краевую вену уха в/в при помощи иглы-катетера «Cathy» («HMD», Индия) вводили водный раствор плацебо (3,75 М раствор мочевины, соответствующий ее концентрации в растворе ФМ), в объеме 0,5 мл, затем через 1 час проводили лапаротомию и наносили стандартную травму печени в соответствии с имеющимися рекомендациями [9] в условиях общей анестезии препаратом Телазол («Зоэтис», Россия), в/в 10 мг/кг. Для исследования системы гемостаза кровь получали из краевой вены уха (самотеком) после флеботомии дважды — перед введением препаратов и нанесением травмы печени При микроскопии раневой поверхности фибрин выглядел в виде тонких «нежных» волокон В синусоидных капиллярах в непосредственной близости от травмы были видны небольшие скопления тонких фибриновых волокон, а также единичные эритроциты с четкими границами между клетками.

After placebo administration
Показатель Parameter
After streptokinase and placebo administration
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