Therapeutic Fibrinolysis: How Efficacy and Safety Can Be Improved.
Therapeutic fibrinolysis has been dominated by the experience with tissue-type plasminogen activator (t-PA), which proved little better than streptokinase in acute myocardial infarction. In contrast, endogenous fibrinolysis, using one-thousandth of the t-PA concentration, is regularly lysing fibrin and induced Thrombolysis In Myocardial Infarction flow grade 3 patency in 15% of patients with acute myocardial infarction. This efficacy is due to the effects of t-PA and urokinase plasminogen activator (uPA). They are complementary in fibrinolysis so that in combination, their effect is synergistic. Lysis of intact fibrin is initiated by t-PA, and uPA activates the remaining plasminogens. Knockout of the uPA gene, but not the t-PA gene, inhibited fibrinolysis. In the clinic, a minibolus of t-PA followed by an infusion of uPA was administered to 101 patients with acute myocardial infarction; superior infarct artery patency, no reocclusions, and 1% mortality resulted. Endogenous fibrinolysis may provide a paradigm that is relevant for therapeutic fibrinolysis.
Vascular Research Laboratory, Mount Auburn Hospital, Cambridge, Massachusetts, and Harvard Medical School, Cambridge, Massachusetts. Electronic address: vgurewich@tsillc.net.
Victor
V
Gurewich
D006801:Humans; D015912:Thrombolytic Therapy / Q000379:methods* / Q000639:trends; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D010959:Tissue Plasminogen Activator
endogenous lysis; plasminogen activator inhibitor; streptokinase; synergy; tissue plasminogen activator; urokinase-type plasminogen activator