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Toxicologic Pathology
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Platelet Kinetics in Dogs Treated with a Glycoprotein IIb/IIIa Peptide Antagonist

Douglas J. Weiss

Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108, weiss005{at}tc.umn.edu

Michael L. Mirsky

Department of Pathology, Rhone-Poulenc Rorer, 55 Arcola Road NW7, Collegeville, Pennsylvania 19426

Oral A. Evanson

Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108

Jose Fagliari

Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108

David Mcclenahan

Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108

Bruce Mccullough

Department of Pathology, Rhone-Poulenc Rorer, 55 Arcola Road NW7, Collegeville, Pennsylvania 19426

Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists have been highly effective inhibitors of platelet aggregation in preclinical studies and in clinical trials. However, decreased platelet counts have been documented in preclinical studies and in some patients receiving GPIIb/IIIa antagonists. We evaluated changes in platelet kinetics and fate in dogs receiving the GPIIb/IIIa receptor antagonist RPR 109891 orally for 4 days. Dogs receiving RPR 109891 had a 22-52% decrease in platelet count with the nadirs at 3-5 days after initiation of treatment. Platelet survival time was reduced by 19%, and platelet half-life was reduced by 63%. Indium-111-labeled platelets were rapidly cleared from the blood within 1 hour after administration of RPR 109891 on treatment days 1 and 2. This clearing was associated with a sharp increase in radioactivity in spleen but not in liver or lung. Platelet clearance was markedly attenuated on treatment days 3 and 4. Platelet counts returned to baseline within 1 week after discontinuation of treatment. These data indicate that RPR 109891 causes rapid and selective sequestration of platelets in the spleen.

Key Words: Thrombocytopenia • RPR 109891 • platelet survival • scintigraphy

Toxicologic Pathology, Vol. 28, No. 2, 310-316 (2000)
DOI: 10.1177/019262330002800211
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