Fibrin specificity of plasminogen activators, rebound generation of thrombin, and their therapeutic implications.
Optimal induction of coronary thrombolysis depends in part upon the nature of the specific plasminogen activator used. The two general classes of plasminogen activators available clinically differ in a fundamental respect delineated by the term, clot selectivity. Clot selective agents are less prone to induce plasminemia and consequent occult activation of the coagulation cascade than are non-selective agents. However, under clinical conditions, all plasminogen activators result in some activation of the cascade with consequent generation of thrombin. Accordingly, optimal therapy requires the use of conjunctive anticoagulation to preclude the deleterious effects of rebound generation of thrombin, which has been well documented biochemically. The potential value of antiplatelet agents that can attenuate the positive feedback loop between activation of platelets and markedly amplified generation of thrombin in the setting of coronary thrombolysis is under active exploration. With appropriate monitoring of the efficacy of such agents in vivo it should be possible to enhance even further the benefits that can be conferred by pharmacologically induced coronary thrombolysis.
Sobel
B E
BE
Department of Medicine, University of Vermont, College of Medicine, Burlington, USA.
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage; D001777:Blood Coagulation; D004285:Dogs; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D010960:Plasminogen Activators / Q000145:classification / Q000378:metabolism / Q000627:therapeutic use*; D011817:Rabbits; D009626:Terminology as Topic; D013917:Thrombin / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D005337:Fibrin; D010960:Plasminogen Activators; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D001241:Aspirin