Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential?

T HROMBOTIC COMPLICATIONS of cardiovascular disease are a main cause of death and disability and, consequently, thrombolysis could favorably influence the outcome of such life-threatening diseases as myocardial infarction, cerebrovascular thrombosis, and venous thromboembolism. Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic system in blood, to the proteolytic enzyme plasmin. Plasmin dissolves the fibrin of a blood clot, but may also degrade normal components of the hemostatic system and induce the so-called "lytic state." However, physiologic fibrinolysis is fibrin-oriented as a result of specific molecular interactions between tissue-type plasminogen activator (tPA), fibrin, plasmin(ogen), and a,-antiplasmin.' Currently, six thrombolytic agents are either approved for clinical use or under clinical investigation in patients with acute myocardial infarction. These include streptokinase, urokinase, recombinant t-PA (rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC), recombinant single-chain urokinase-type. plasminogen activator (rscu-PA; recombinant prourokinase), and recombinant staphylokinase (Sak)? In patients with acute myocardial infarction, reduction of infarct size, preservation of ventricular function, a n d or reduction in mortality has been observed after treatment with either streptokinase, rt-PA, or APSAC.' This review will focus on the biochemical and thrombolytic properties of staphylokinase, a bacterial protein with profibrinolytic properties that would appear to have potential for treatment of acute myocardial infarction.