Mechanism of action and thrombolytic potential of staphylokinase.
Staphylokinase is a profibrinolytic agent that forms a 1:1 stoichiometric complex with plasminogen that, after conversion to plasmin, activates other plasminogen molecules to plasmin. The plasmin.staphylokinase complex, unlike the plasmin.streptokinase complex, is rapidly inhibited by alpha2-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 alpha2-antiplasmin of plasmin.staphylokinase complex bound to fibrin, recycling of staphylokinase from the plasmin.staphylokinase complex following inhibition by alpha2-antiplasmin, and prevention of the plasminogen.staphylokinase to plasmin.staphylokinase. In experimental animal models, staphylokinase appears to be equipotent to streptokinase for the dissolution of whole blood or plasma clots, but more potent for the dissolution of platelet-rich or retracted thrombi. The thrombolytic potential of recombinant staphylokinase is presently under investigation in pilot studies in patients with acute myocardial infarction or with peripheral arterial occlusion. Definition of the therapeutic benefit of recombinant staphylokinase will require more detailed dose-finding studies followed by randomized efficacy studies against other thrombolytic agents.
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Centrum voor Moleculaire en Vasculaire Biologie Faculteit Geneeskunde Katholieke Universiteit Leuven.
D000818:Animals; D006224:Cricetinae; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008666:Metalloendopeptidases / Q000494:pharmacology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy; D011817:Rabbits; D011994:Recombinant Proteins; D013927:Thrombosis / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus