Modulation of platelet-neutrophil interaction with pharmacological inhibition of fibrinogen binding to platelet GPIIb/IIIa receptor

The study investigated how drug inhibition of the GPIIb/IIIa receptor influ ences the interactions between platelets and leukocytes. These interactions are believed to play an important role in the etiology of the acute corona ry syndromes. Thirty patients with unstable angina or non-Q-wave myocardial infarction were studied before the administration of tirofiban or placebo and after 4 h and 72 h, Platelet-leukocyte aggregates were characterized in whole blood using three-colour flow cytometry. The leukocyte population wa s isolated by a nucleic acid probe (LDS 751) and platelet-neutrophil coaggr egates identified as particles binding both anti-CD42a-FITC and anti-CD45-P E. Tirofiban decreased by 25% the density of platelets in circulating plate let-neutrophil coaggregates (p <0.01), and prevented the increase induced b y platelet agonist stimulation (p <0.0001). The reduction correlated with i nhibition of fibrinogen binding to platelet (p <0.0001) and with inhibition of platelet aggregation (p < 0.0001). The percentage of neutrophils with b ound platelets following platelet agonist stimulation was, however, increas ed following GPIIb/IIIa inhibition. Thus, inhibition of GPIIb/IIIa receptor promotes platelet-neutrophil adhesion, but markedly reduces the binding de nsity of platelets in the coaggregates.