Basic and Clinical Aspects of Fibrinolysis and Thrombolysis

Cardiovascular diseases, mainly comprising coronary artery disease leading to myocardial infarction, cerebrovascular disease causing strokes, and venous thrombosis predisposing to pulmonary embolism and the post-phlebitic syndrome, are a major cause of death and disability. The triggering event in the clinical expression of the acute ischemic event is not the underlying atherosclerotic lesion, but a thrombotic obstruction of the artery. Thus, the common cardiovascular diseases have, as their immediate underlying etiology, thrombosis of critically situated blood vessels with loss of blood flow to vital organs. One approach to the treatment of thrombosis consists of the pharmacologic dissolution of the blood clot via the intravenous infusion of PAS. Currently, five thrombolytic agents are either approved for clinical use or under clinical investigation in patients with acute myocardial infarction. These agents are streptokinase (SK), two-chain u-PA (tcu-PA; urokinase), anisoylated plasminogen streptokinase activator complex (APSAC), recombinant t-PA (rtPA), and recombinant single-chain u-PA (rscu-PA; prourokinase).] Reduction of infarct size, preservation of ventricular function, and reduction in mortality has been obtained with SK, rt-PA, and APSAC.' Consequently, thrombolytic therapy has become standard treatment for early acute myocardial infarction. Intravenous SK recanalizes approximately 50% of occluded coronary arteries within 90 minutes and reduces mortality by 25%. rt-PA in combination with adjunctive intravenous heparin is more potent for coronary arterial thrombolysis, producing both more rapid and more frequent recanalization (patency 70% to 75% within 90 minutes). Side effects (mainly bleeding) and the incidence