Morphologic, Hemostasiologic and Hemostatic Aspects of Systemic Application of Exogenous Fibrin Monomer in Model of Posttraumatic Bleeding with Underlying Intake of Warfarin

Abstract

INTRODUCTION: Earlier, an ability of exogenous fibrin monomer (FM) introduced at low doses to considerably limit posttraumatic blood loss was established by us on an experimental model of warfarin coagulopathy in vivo. However, the morphologic peculiarities of fibrin formation in the wound area were not considered.

AIM: To compare morphologic, hemostasiologic and hemostatic data based on the results of systemic application of exogenous FM to interpret their effects in the model of posttraumatic bleeding with the underlying intake of warfarin.

MATERIALS AND METHODS: In the work, Chinchilla male rabbits were used. A comparative analysis of hemostasiologic effects and of morphologic picture of the surface of the liver in the wound area was conducted after a dosed trauma, with a preliminary systemic introduction of FM (0.25 mg/kg intravenously) or a concentrate of prothrombin complex factors (40 IU/kg intravenously) with the underlying intake of warfarin by animals (0.4–0.5 mg/kg/day per os for 2 weeks).

RESULTS: Introduction of FM in warfarinised animals in the conditions of a dosed experimental liver injury promoted a hemostatic effect comparable with that of a concentrate of prothrombin complex factors. Both hemostatic drugs led to intense fibrin formation that reduced posttraumatic blood loss. The use of FM was associated with increase in the thickness of thrombotic deposits and fibrin fibers in the wound surface in comparison with placebo by 4.0 and 1.6 times, respectively (р < 0.000001). This process actively involved platelets, which led to 1.7 times reduction of their quantity in the lumen of the blood vessels in the wound vicinity (р < 0.0002). No effect of FM on systemic hemostatic reactions in venous blood was found, in contrast to concentrate of prothrombin complex factors.

CONCLUSION: Exogenous FM can produce a local hemostatic effect in the conditions of dosed experimental trauma and coagulopathy induced by warfarin intake. The hemostatic effect was mediated by intense thrombosis on the wound surface with the active recruitment of platelets in the process. The peculiarities of the demonstrated effects of FM may be mediated though the mechanisms of its action that have not yet been identified, which necessitates continuation of the research in this direction.

Keywords

fibrin monomer / warfarin / concentrate of prothrombin complex factors / hepatic injury / bleeding arrest / fibrin formation

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Vdovin V.M., Shakhmatov I.I., Bobrov I.P., Orekhov D.A., Teryayev V.V., Chernus' V.E., Momot A.P.