Medical Dictionary

thrombolytic therapy

1. intravenous administration of an agent intended to dissolve a clot causing acute ischemia, as in myocardial infarction (MI), stroke, and peripheral arterial or venous thrombosis. Thrombolytic agents degrade fibrin clots by activating plasminogen, a naturally occurring modulator of hemostatic and thrombotic processes. Synthesized by the liver, plasminogen is present in circulating blood and binds to platelets, endothelium, and fibrin. At sites of vascular injury with thrombus formation, tissue plasminogen activator (TPA), produced by endothelial cells, also binds to fibrin and converts fibrin-bound plasminogen to plasmin by cleaving the arginine-valine bond in the 560–561 position of plasminogen. The resulting clot lysis is due to degradation of fibrin threads as well as of glycoproteins required for platelet adhesion and aggregation. Thrombolytic agents in current use mimic the effects of natural TPA. These include alteplase, a TPA produced by recombinant DNA technology; reteplase, a variant of the TPA molecule, also genetically engineered; urokinase, a tissue protein derived from human kidney cell cultures; streptokinase, a product of β-hemolytic streptococci that catalyzes the conversion of plasminogen to plasmin; and anistreplase, an inactive form of plasminogen that is bound to streptokinase and undergoes deacylation after administration, resulting in persistent activation of plasminogen. The latter two products are potentially antigenic and can cause systemic hypersensitivity reactions. See also: tissue plasminogen activator