Modulating the balance between coagulation and fibrinolysis. Coagulation initiated by tissue factor exposed at sites of vascular injury results in thrombin generation. Thrombin converts fibrinogen to fibrin and activates platelets, which leads to thrombosis. Feedback activation of FXI by thrombin amplifies thrombin generation. FXI also can be activated via the intrinsic pathway when FXII is activated by collagen exposed at sites of denuding vascular injury or by polyphosphate released from activated platelets. Therefore, inhibitors of FXII or FXI have the potential to attenuate thrombosis. Plasmin (Pn) degrades fibrin to effect fibrinolysis. Plasminogen (Pg) is activated by tissue plasminogen activator (tPA). Fibrinolysis can be enhanced by inhibiting α₂-antiplasmin (α₂AP), the major inhibitor of Pn, or by inhibiting activated TAFIa. TAFIa attenuates fibrinolysis by releasing C-terminal lysine and arginine residues from degrading fibrin, thereby removing binding sites for Pg and tPA. TAFI is activated by thrombin after it binds to thrombomodulin on the cell surface, a process that links coagulation and fibrinolysis.