Lack of interference by heparin with thrombolysis or binding of tissue-type plasminogen activator to thrombi.

Coronary thrombolysis with t-PA is generally implemented with concomitant administration of heparin. However, results of studies in vitro suggest that heparin competes with fibrin for binding of tissue-type plasminogen activator (t-PA), augments activation of free plasminogen, decreases fibrin specificity, and impairs thrombolysis. To define the biological implications of these observations, we characterized effects of therapeutic concentrations of heparin on the binding of t-PA to thrombi formed in whole blood, effects of heparin on activation of plasminogen by t-PA in plasma, and effects of heparin on thrombolysis induced by t-PA in a clot lysis system designed to simulate conditions in vivo. The amount of t-PA bound to thrombi was not affected by heparin (0, 0.5, 1.0, and 5.0 U/mL). When t-PA activity was selectively and irreversibly inhibited by D-Phe-Pro-Arg-chloromethyl ketone (PPACK) the amount of t-PA-PPACK bound was similarly unaffected by heparin. Thrombolysis measured by 125I-fibrin(ogen) release and by reduction of mass of thrombi were not altered by heparin. Heparin did not affect plasminogen consumption induced by t-PA. Plasma concentrations of alpha-2-antiplasmin after exposure of blood to t-PA were less depressed with increasing concentrations of heparin. Thus, heparin in therapeutic concentrations does not interfere with binding of t-PA to thrombi, augment activation of free plasminogen, or inhibit thrombolysis. Accordingly, it appears likely that concomitant administration of heparin will not impair thrombolysis with t-PA implemented clinically.