Overview This schematic shows the mechanism of thrombolysis. Plasminogen is cleaved into plasmin by tPA, urokinase, factor XIa, XIIa, and kallikrein. Plasmin then then degrades fibrin. Thrombolytics catalyze the formation of endogenous plasmin from plasminogen precursor plasmin is a serine protease that degrades clots (thrombi) Drugs tPA (alteplase) streptokinase urokinase APSAC (anistreplase) Mechanism catalyze conversion of plasminogen to plasmin cleaves fibrin clots cleaves thrombin clot-specificity tPA is clot-specific acts only on fibrin-bound plasminogen streptokinase is not clot specific depletes circulating plasminogen, factor V, factor VIII ↑ PT, ↑ PTT, no change in platelet count Clinical use administer as early as possible following ischemic stroke (tPA) MI DVT pulmonary embolism Toxicity bleeding and intracerebral hemorrhage contraindicated in patients with history of bleeding, surgery, hypertension streptokinase may cause hypersensitivity derived from β-hemolytic streptococci Antagonist aminocaproic acid and tranexamic acid lysine analog that prevents conversion of plasminogen to plasmin inhibitor of fibrinolysis