Staphylokinase: fibrinolytic properties and current experience in patients with occlusive arterial thrombosis

Staphylokinase is a profibrinolytic agent that forms a 1:1 stoichiometric complex with plasminogen which, following conversion to plasmin, activates other plasminogen molecules to plasmin. The plasmin, staphylokinase complex, unlike the plasmin, streptokinase complex, is rapidly inhibited by alpha 2-antiplasmin. In a plasma milieu, staphylokinase is able to dissolve fibrin clots without associated fibrinogen degradation. This fibrin-specificity of staphylokinase is the result of reduced inhibition by alpha 2-antiplasmin of plasmin, staphylokinase complex bound to fibrin, recycling of staphylokinase from the plasmin, staphylokinase complex following inhibition by alpha 2-antiplasmin, and prevention of the conversion of plasminogen, staphylokinase to plasmin, staphylokinase by alpha 2-antiplasmin. In several experimental animal models, staphylokinase appears to be equipotent to streptokinase for the dissolution of whole blood or plasma clots, but significantly more potent for the dissolution of platelet-rich or retracted thrombi. The feasibility of fibrin-specific coronary thrombolysis with an intravenous infusion over 30 min of 10 mg recombinant staphylokinase was demonstrated in two small pilot studies in patients with acute myocardial infarction with angiographically confirmed total occlusion of the infarct-related coronary artery. However, neutralizing antibodies against staphylokinase were demonstrable from the third week on in all patients. Definition of the therapeutic benefit of recombinant staphylokinase will require more detailed dose-finding studies followed by randomized efficacy studies against other thrombolytic agents. An interim analysis after 50 patients of a randomized trial of recombinant tissue-type plasminogen activator versus staphylokinase in patients with acute myocardial infarction revealed similar rates of coronary patency at 90 minutes but a significantly higher fibrin specificity of the latter compound.