Thrombin-activatable Fibrinolysis Inhibitor: Interplay between Fibrinolysis and Thrombosis

Abstract Thrombin-activatable fibrinolysis inhibitor (TAFI) is a metallocarboxypeptidase that is activated by plasmin, thrombin, or thrombomodulin/thrombin complex. When fibrin is degraded by plasmin, new carboxy-terminal lysine residues are formed on the fibrin surface that serve as binding sites for plasminogen and tissue plasminogen activator and hence facilitate plasmin generation and augment fibrin degradation. These residues are readily removed by activated TAFI (TAFIa), which deprives fibrin of its cofactoring role in plasmin generation and imposes an antifibrinolytic state. In addition, several single-nucleotide polymorphisms in the TAFI gene have been identified and are associated with increased TAFI antigen levels and a more profound effect on fibrinolysis. Owing to its antifibrinolytic properties and thrombotic predisposition, it has drawn increasing interest in investigating the therapeutic potential of targeting the TAFI/TAFIa system. This review discusses recent findings in TAFI research, including its activation and its effects on fibrinolysis and other pathological conditions.