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SYSTEMIC HEMOSTATIC AND PROTHROMBOTIC EFFECTS OF FIBRIN-MONOMER IN EXPERIMENT WITH DOSED LIVER THERAPY

https://doi.org/10.15372/SSMJ20190101

Abstract

Objective of the study is to experimentally evaluate system hemostatic and prothrombotic effects of intravenous fibrin monomer (FM). 

Materials and methods. Eighty two Chinchilla rabbits weighing 3–4 kg were used in the study. In addition to the placebo, animals were administered an aqueous solution of fibrin monomer (FM) intravenously at doses of 0.1, 0.25, 0.5, 1.0, 2.5 and 5.0 mg/kg. After 1 hour, a standard liver injury was performed and the blood loss (% of the circulating blood volume) resulting from parenchymal hemorrhage was estimated. Hemostatic system examination included platelet number in venous blood and fibrinogen and D-dimer levels in blood plasma. 

Results and discussion. Blood loss after dosed injury with placebo was 10.0 [4.0; 15.7] % blood volume (median [25th percentile; 75th percentile]). FM preparation doses of 0.25, 2.5 and 5.0 mg/kg resulted in a decrease of blood loss by 6.3 (p < 0.001), 7.8 (p < 0.001) and 2.7 times (p = 0.04) (1.6 [1.0; 3.0], 1.3 [0.6; 1,6] and 3.7 [2.8; 5.3] % blood volume, respectively).High doses of FM preparation (2.5 and 5.0 mg/kg) minimized blood loss due to activation of coagulation and thrombus formation, which was illustrated by a 7.0–8.0-fold increase in D-dimer level (compared to placebo). 0.25 mg/kg of FM preparation did not lead to an increase of D-dimer content, although the blood loss was greatly reduced. 

Conclusion. The data obtained show the presence of unique hemostatic properties in low-dose FM preparation (0.25 mg/kg), which allows creating system hemostatic agents of a new generation.

About the Authors

A. P. Momot
National Research Center for Hematology of Minzdrav of Russia, Altai Branch; Research Institute of Physiology and Fundamental Medicine
Russian Federation

Andrey Pavlovich Momot – doctor of medical sciences, professor, director 

656045, Barnaul, Lyapidevskogo str., 1;

630117, Novosibirsk, Timakov str., 4



V. M. Vdovin
Altai State Medical University of Minzdrav of Russia; Research Institute of Physiology and Fundamental Medicine
Russian Federation

Vyacheslav Mikhaylovich Vdovin – candidate of medical sciences, associate professor, head of the department of pathological physiology  

656038, Barnaul, Lenin av., 40;
630117, Novosibirsk, Timakov str., 4



I. I. Shakhmatov
Altai State Medical University of Minzdrav of Russia; Research Institute of Physiology and Fundamental Medicine
Russian Federation

Igor Ilyich Shakhmatov – doctor of medical sciences, professor, head of the department of normal physiology 

656038, Barnaul, Lenin av., 40; 
630117, Novosibirsk, Timakov str., 4



I. G. Tolstokorov
Consulting Diagnostic Center «Dobryi Doktor» Ltd
Russian Federation

Igor Gennadievich Tolstokorov – surgeon

656006, Barnaul, Baltiyskaya str., 4a



D. A. Orekhov
Altai Regional Cardiology Health Center
Russian Federation

Dmitriy Andreevich Orekhov – surgeon

656055, Barnaul, Malakhov str., 46



V. O. Shevchenko
Consulting Diagnostic Center «Dobryi Doktor» Ltd.
Russian Federation

Valentin Olegovich Shevchenko – surgeon

656006, Barnaul, Baltiyskaya str., 4a



N. A. Lycheva
Altai State Medical University of Minzdrav of Russia; Research Institute of Physiology and Fundamental Medicine
Russian Federation

Natalya Alexandrovna Lycheva – candidate of biological sciences, associate professor of the department of normal physiology

656038, Barnaul, Lenin av., 40; 
630117, Novosibirsk, Timakov str., 4



A. V. Kudinov
Altai State Medical University of Minzdrav of Russia
Russian Federation

Alexey Vladimirovich Kudinov– candidate of biological sciences, associate professor of the department of pharmacology 

656038, Barnaul, Lenin av., 40



G. G. Belozerskaya
National Research Center for Hematology of Minzdrav of Russia
Russian Federation

Galina Gennadievna Belozerskaya – doctor of medical sciences, head of laboratory of pathology and pharmacology of hemostasis

125167, Moscow, Novyy Zykovsky dr., 4



V. I. Kiselev
Altai State Medical University of Minzdrav of Russia; Research Institute of Physiology and Fundamental Medicine
Russian Federation

Valeriy Ivanovich Kiselev – corresponding member of RAS, doctor of medical sciences, professor of the department of normal physiology

656038, Barnaul, Lenin av., 40; 
630117, Novosibirsk, Timakov str., 4



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