Circulation, Vol 80, 1766-1774, Copyright © 1989 by American Heart Association
BS Coller, JD Folts, SR Smith, LE Scudder and R Jordan
We studied the dose-response effects of the F(ab')2 fragments of murine
monoclonal antibodies to the platelet GPIIb/IIIa receptor (7E3 and 10E5) on
in vivo platelet thrombus formation in a well-characterized monkey model in
which the carotid artery is stenosed and thrombus formation is provoked and
augmented by intimal damage and the infusion of subaggregating doses of
epinephrine. Both antibodies abolished thrombus formation with a mean dose
of -0.2 mg/kg. Ex vivo platelet aggregation was not always abolished at
doses that abolished thrombus formation; similarly, bleeding times were
only moderately prolonged (9.1 +/- 1.4 minutes) at these doses. Increasing
the dose above that required to abolish thrombus formation consistently
produced abolition of ex vivo platelet aggregation, marked prolongation of
the bleeding time (14.2 +/- 1.5 minutes), and nearly quantitative blockade
of GPIIb/IIIa receptors. We conclude that in a significant percentage of
animals, the extent of GPIIb/IIIa blockade required to prevent
vasoocclusive thrombus formation in this model is less than that required
for abolition of platelet aggregation, and that the preservation of only a
minority of functional GPIIb/IIIa receptors might be adequate to maintain a
nearly normal bleeding time.
ARTICLES
Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors
Department of Medicine, State University of New York at Stony Brook 11794.
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