Circulation, Vol 83, 1048-1056, Copyright © 1991 by American Heart Association
EJ Haskel, NA Prager, BE Sobel and DR Abendschein
BACKGROUND. Optimal coronary thrombolysis should be prompt and persistent.
Although activation of platelets and increased thrombin activity have been
associated with clinical thrombolysis, the role of each in delaying
thrombolysis or inducing early coronary reocclusion has been difficult to
define. METHODS AND RESULTS. In conscious dogs with coronary thrombosis
induced by electrical current, we assessed the impact on the rapidity of
thrombolysis and the incidence of reocclusion of two types of adjunctive
treatment given concomitantly with intravenous tissue-type plasminogen
activator (t-PA): 1) inhibition of platelet function with a peptide mimetic
antagonist of platelet glycoprotein IIb/IIIa receptors or with lysine
acetylsalicylic acid (ASA) and 2) inhibition of thrombin activity with
recombinant hirudin or with heparin. ASA but not the receptor antagonist
shortened the time to thrombolysis with t-PA (20 +/- 13 [mean +/- SD]
minutes with ASA, 36 +/- 15 minutes with receptor antagonist, and 43 +/- 16
minutes with the saline control). Reocclusion occurred promptly after
completion of the infusion of t-PA in all seven dogs given saline.
Reocclusion was delayed and prevented in some dogs within 90 minutes after
the end of the infusion of t-PA by both antiplatelet agents but still
occurred in 42% despite continued inhibition of platelet function (i.e.,
three of six dogs given ASA and two of six given receptor antagonist). In
contrast, inhibition of thrombin activity with recombinant hirudin in a
dose that prolonged the partial thromboplastin time modestly (1.5-2- fold)
resulted in accelerated lysis (19 +/- 10 minutes) and prevention of
reocclusion in each of six dogs. Heparin given in doses that elicited
similar prolongation of the partial thromboplastin time did not accelerate
lysis nor prevent reocclusion, which occurred in five of six dogs.
CONCLUSIONS. Inhibition of thrombin by recombinant hirudin facilitates
thrombolysis and maintains patency of coronary arteries recanalized with
t-PA particularly effectively. The benefit conferred may reflect direct
anticoagulant effects plus diminished activation of platelets secondary to
decreased thrombin activity.
ARTICLES
Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.
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