Fagliari Jj

Platelet kinetics in dogs treated with a glycoprotein IIb/IIIa peptide antagonist

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.

Haemorrheology of Equine Platelet-Neutrophil Aggregates

The filterability of platelet-neutrophil aggregates through filters containing 5 μm pores was determined to evaluate the potential of plateletneutrophil aggregates to alter blood flow in the microvasculature. Incubation of platelet-neutrophil mixture with platelet-activating factor (PAF) and with 0.5 μM adenosine diphosphate (ADP) resulted in large platelet-neutrophil aggregates which rapidly plugged filter pores. Incubation of platelet-neutrophil mixtures with lower concentrations of ADP resulted in small platelet-neutrophil aggregates that contained only one neutrophil. Filtration of these samples resulted in a 1.3-, 3.2- and 3.7-fold increase in initial filtration pressure at ADP concentrations of 0.05, 0.15 and 0.25 μM, respectively. We conclude that platelet-neutrophil aggregates have reduced deformability and may alter blood flow in the microvasculature.