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  • Title: Fibrinolytic agents: mechanisms of activity and pharmacology.
    Author: Lijnen HR, Collen D.
    Journal: Thromb Haemost; 1995 Jul; 74(1):387-90. PubMed ID: 8578491.
    Abstract:
    Fibrinolytic (thrombolytic) agents activate the fibrinolytic system by conversion of the inactive proenzyme, plasminogen into the active enzyme plasmin, that degrades fibrin. Agents available for clinical use are: the physiologic tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA)--either in a single chain (scu-PA, prourokinase) or a two-chain (tcu-PA, urokinase) form, and the bacterial activator plasminogen streptokinase or its anisoylated complex with plasminogen (APSAC). Despite their widespread use, mainly in patients with acute myocardial infarction, all these agents suffer from a number of significant limitations, including resistance to reperfusion, the occurrence of acute coronary reocclusion and bleeding complications. Several lines of research towards improvement of thrombolytic agents are being explored, including the construction of mutants and variants of plasminogen activators, chimeric plasminogen activators, or plasminogen activators from animal (e.g. vampire bat) or bacterial (e.g. staphylokinase) origin. Pilot studies in patients with acute myocardial infarction have been performed with a few selected agents. Definition of their relative therapeutic benefit, or lack thereof, will require more detailed dose-finding studies, followed by randomized clinical trials against presently available thrombolytic agents.
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