The paradoxical antifibrinolytic effect of dabigatran and argatroban in the presence of soluble thrombomodulin is unrelated to protein C-dependent increase of thrombin generation

Our results suggest that the inhibition of PC activation by DTIs in the presence of TM, while enhancing thrombin generation, has no effect on thrombin-mediated TAFI activation. The inhibition of fibrinolysis by DTIs can be explained by the prolonged activation of TAFI resulting from the sustained release of thrombin from thrombin-DTI complex. While the clinical relevance of these findings needs to be investigated by in vivo studies, our data might help understanding the role of the different players in the regulation of thrombin generation, TAFI activation and fibrinolysis resistance.