Inhibition of Fibrinolysis by Coagulation Factor XIII

Abstract

The inhibitory effect of coagulation factor XIII (FXIII) on fibrinolysis has been studied for at least 50 years. Our insight into the underlying mechanisms has improved considerably, aided in particular by the discovery that activated FXIII cross-linksα2-antiplasmin (α2AP) to fibrin. In this review, the most important effects of different cross-linking reactions on fibrinolysis are summarized. A distinction is made between fibrin-fibrin cross-links studied in purified systems and fibrin-α2AP cross-links studied in plasma or whole blood systems. While the formation ofγchain dimers in fibrin does not affect clot lysis, the formation ofαchain polymers has a weak inhibitory effect. Only strong cross-linking of fibrin, associated with high molecular weightαchain polymers and/orγchain multimers, results in a moderate inhibition fibrinolysis. The formation of fibrin-α2AP cross-links has only a weak effect on clot lysis, but this effect becomes strong when clot retraction occurs. Under these conditions, FXIII preventsα2AP being expelled from the clot and makes the clot relatively resistant to degradation by plasmin.