EFFECTS OF TRANEXAMIC ACID, FACTOR XIII, AND FIBRINOGEN ON CLOT FORMATION AND LYSIS IN THE MODEL OF HYPERFIBRINOLYSIS INDUCED BY TISSUE- VS UROKINASE-TYPE PLASMINOGEN ACTIVATOR

Aim of the study. To compare the effects of tranexamic acid (TXA), factor XIII concentrate (FXIII) and fibrinogen concentrate on clot formation and fibrinolytic resistance in the in vitro model of hyperfibrinolysis induced by tissue- (tPA) vs urokinase-type (uPA) plasminogen activators.
Materials and methods. Citrated whole blood from 28 adult healthy volunteers was supplemented with 10 μg/ mL TXA, 2 IU/mL FXIII, or 3 mg/mL fibrinogen concentrate. Hyperfibrinolysis was induced by spiking the blood with tPA or uPA at their half-maximal effective concentrations (90 and 33 IU/mL, respectively). Clotting was induced by recalcification and addition of tissue factor and monitored using rotation thromboelastometry.
Results. The use of TXA increased maximal clot firmness in the presence of tPA and markedly inhibited clot lysis in the presence of any of the plasminogen activators. Supplementation of blood with FXIII significantly increased clot firmness and improved fibrinolytic resistance in the presence of either tPA or uPA. Supplementation with fibrinogen concentrate elicited a strikingly different effect on clot formation and lysis depending on the type of plasminogen activator. In the presence of tPA, fibrinogen concentrate significantly increased clot firmness and attenuated clot lysis. In contrast, in the presence of uPA, the use of fibrinogen markedly reduced clot firmness and promoted clot lysis. Similar effects of fibrinogen concentrate were observed in platelet-rich and microparticles-free plasma.
Conclusion. In hyperfibrinolysis, effect of the hemostatic drugs significantly depends on the type of plasminogen activator used. Therefore, mechanisms of hyperfibrinolysis should be taken into consideration while administering hemostatic drugs.

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