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

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Abstract

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 Shapiro–Wilk test. Statistical differences between groups were tested by Student’s t-test, Mann–Whitney 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.

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About the authors

V M Vdovin

Altai State Medical University; State Research Institute of Physiology and Fundamental Medicine

Author for correspondence.
Email: erytrab@gmail.com
Russian Federation, Barnaul, Russia; Novosibirsk, Russia

A P Momot

Altai State Medical University; Altai Branch of FSBI, National Research Center for Hematology; State Research Institute of Physiology and Fundamental Medicine

Email: erytrab@gmail.com
Russian Federation, Barnaul, Russia; Barnaul, Russia; Novosibirsk, Russia

D A Orekhov

Altay Regional Dispensary of Cardiology

Email: erytrab@gmail.com
Russian Federation, Barnaul, Russia

I I Shakhmatov

Altai State Medical University; State Research Institute of Physiology and Fundamental Medicine

Email: erytrab@gmail.com
Russian Federation, Barnaul, Russia; Novosibirsk, Russia

N A Lycheva

State Research Institute of Physiology and Fundamental Medicine

Email: erytrab@gmail.com
Russian Federation, Novosibirsk, Russia

D A Momot

Altai State Medical University

Email: erytrab@gmail.com
Russian Federation, Barnaul, Russia

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2. Рис. 1. Дизайн экспериментов с дозированной травмой печени; ФМ — фибрин-мономер

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3. Рис. 2. Сравнительный анализ геморрагических проявлений кровопотери у экспериментальных животных после дозированной травмы печени; ОЦК — объём циркулирующей крови. Значения представлены в виде медианы — горизонтальной линии внутри прямоугольника, включающего 50% полученных значений, и значений, соответствующих 2,5 и 97,5 перцентиля — нижний и верхний вертикальные бары

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© 2020 Vdovin V.M., Momot A.P., Orekhov D.A., Shakhmatov I.I., Lycheva N.A., Momot D.A.

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