Regulation of fibrinolysis by plasminogen activator inhibitor-1 (PAI-1), α2-antiplasmin, and thrombin-activatable fibrinolysis inhibitor (TAFI)

PAI-1 inhibits plasmin formation by inhibiting t-PA. α₂-antiplasmin inhibits the activity of plasmin, thereby inhibiting fibrinolysis. TAFI circulates in plasma as a zymogen. It is activated by thrombin when thrombin is bound on to its endothelial cofactor TM, and therefore represents a link between blood coagulation and fibrinolysis. During fibrinolysis, plasmin cleaves intact fibrin at lysine residues, initially yielding large, insoluble fibrin fragments with lysine residues at their carboxyl termini. Plasminogen binds avidly to C-terminal lysine residues within the partially degraded fibrin clot and assumes a conformation that is susceptible to activation by t-PA, thereby promoting plasmin formation, continued fibrinolysis ("rapid fibrinolysis"), and generation of smaller, soluble fibrin fragments that are dispersed by flowing blood. Activated TAFI (TAFI_a) is a carboxypeptidase that removes lysine residues from the C-termini of partially degraded fibrin fragments. By removing C-terminal lysine residues from large fibrin fragments in the partially degraded clot, TAFI inhibits recruitment of plasminogen to the clot, thereby slowing fibrinolysis ("slow fibrinolysis").