Comparative analysis of the hemostatic effect of systemic recombinant Factor VIIa and exogenous fibrin monomer in an experimental model of heparinization and posttraumatic blood loss

Vyacheslav M. Vdovin; Вдовин Вячеслав Михайлович; Vyacheslav M. Vdovin; Igor I. Shakhmatov; Шахматов Игорь Ильич; Igor I. Shakhmatov; Natalya A. Lycheva; Лычёва Наталья Александровна; Natalya A. Lycheva; Evgeniy А. Subbotin; Субботин Евгений Александрович; Evgeniy А. Subbotin; Andrey P. Momot; Момот Андрей Павлович; Andrey P. Momot

doi:10.17816/brmma635130

Comparative analysis of the hemostatic effect of systemic recombinant Factor VIIa and exogenous fibrin monomer in an experimental model of heparinization and posttraumatic blood loss

Authors: Vdovin V.M.¹, Shakhmatov I.I.¹, Lycheva N.A.¹, Subbotin E.А.¹, Momot A.P.¹^,2
Affiliations:
1. Altai State Medical University
2. National Medical Research Center of Hematology
Issue: Vol 26, No 4 (2024)
Pages: 569-578
Section: Original Study Article
URL: https://journals.rcsi.science/1682-7392/article/view/285205
DOI: https://doi.org/10.17816/brmma635130
ID: 285205

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Abstract

This article presents the results of a study of the systemic hemostatic action of recombinant Factor VIIa in a rabbit model of heparin-induced coagulopathy and posttraumatic bleeding, compared to the administration of exogenous fibrin monomer. The coagulopathy was induced by a single intravenous injection of unfractionated heparin at a dose of 150 IU/kg 15 minutes before injury. Recombinant Factor VIIa (270 μg/kg) or fibrin monomer (0.25 mg/kg) was used as systemic hemostatic agents. One hour after administrating the agents, a standardized liver injury was inflicted, followed by an assessment of blood loss characteristics. Using rotational thromboelastometry and coagulation tests, animal venous blood was analyzed for coagulation time, alpha angle, clot formation time, maximum clot firmness, clot density at 10 minutes, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen concentration. Pharmacologically induced coagulopathy resulted in shifts to a hypocoagulable profile, associated with severe blood loss (1.9 times, p = 0.028) and high animal mortality (26.1%, p = 0.022) compared to the control group. Preventive administration of fibrin monomer or recombinant Factor VIIa reduced posttraumatic blood loss (by 5.4 times, p < 0.001, and by 2.1 times, p = 0.009, respectively), resulting in a decrease in mortality rates. However, the administration of these agents did not correct the hypocoagulable profile as observed in thromboelastometry and coagulation tests. These data demonstrate the hemostatic effect of both agents, with a more pronounced effect after fibrin monomer administration, and suggest potential use of low doses of fibrin monomer in trauma-related hemorrhage. The mechanism of action of fibrin monomer requires further investigation. Therefore, fibrin monomer, a fibrinogen derivative obtained from blood plasma, could be a valuable candidate for managing wound bleeding in addition to recommended systemic hemostatics.

Keywords

posttraumatic blood loss, heparin, recombinant Factor VIIa, fibrin monomer, hemostasis system, traumatic coagulopathy, systemic hemostatics, thromboelastometry, wound blood loss management

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MD, Dr. Sci. (Medicine), professor, Altai Branch

Russian Federation, Barnaul; Barnaul

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