Comparative analysis of thrombotic safety by using tranexamic acid and a fibrin monomer during the antiplatelet or fibrinolytic therapy in experiment

Abstract

  Introduction. Severe blood loss often leads to death, and it is one of the leading complications of extensive trauma, major operations, and various combat wounds. Tranexamic acid is widely used for blood loss minimization; however, its safety issues have not been resolved yet. Also, the article considers the prospects of using fibrin monomer at low doses to control bleeding in terms of both efficacy and safety. Aim. To compare the thrombotic safety of tranexamic acid and a fibrin monomer in antiaggregant- or streptokinase-induced coagulopathy in experiment. Methods. The prothrombotic effect of intravenous administration of tranexamic acid (15 mg/kg) and fibrin monomer (0.25 mg/kg) was compared in two in vivo models of pharmacologically-induced coagulopathy caused by antiplatelet drugs (acetylsalicylic acid 2.0 mg/kg in combination with clopidogrel 8.0 mg/kg) and streptokinase (150,000 IU/kg). Parameters of the hemostasis system, data of rotational thromboelastometry, and calibrated thrombography were studied. Results. The administration of tranexamic acid during the antiaggregant therapy was accompanied by an increase in D-dimer, a marker of thrombinogenesis and fibrinolysis, while maintaining the blood clot density characteristics. When tranexamic acid was used together with streptokinase, the intensity of thrombin generation increased, and the blood clot formation accelerated. When tranexamic acid was replaced by fibrin monomer, no visible effect of fibrin monomer on the hemostasis parameters or the data of the integrated study methods was observed in either model of coagulopathy. Conclusion. Tranexamic acid when administered systemically reduced wound blood loss and, thus, induced a hypercoagulation shift. The promising hemostatic drug, fibrin monomer, obtained from the blood plasma also reduced the blood loss when administered intravenously but did not cause signs of thrombotic danger. Thus, new data were obtained on the potential and safety of using fibrin monomer for the treatment of post-traumatic hemorrhage.