Lack of interference by heparin with thrombolysis or binding of tissue-
type plasminogen activator to thrombi
ET Fry and BE Sobel
Cardiovascular Division, Washington University School of Medicine, St
Louis, MO 63110.
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.
Volume 71,
Issue 5,
pp. 1347-1352,
05/01/1988
Copyright © 1988 by The American Society of Hematology
