Low incidence of paradoxical platelet activation by glycoprotein IIb/IIIa inhibitors

The human platelet antigen-1 (HPA-1, Pl A) polymorphism has been proposed to influence the inhibitory actions of abciximab. Thus, we hypothesized that this polymorphism might also be the cause for paradoxical activation of platelets by GPIIb/IIIa inhibitors. The effects of abciximab (1–10 μg/ml), tirofiban (3–30 nM), or eptifibatide (0.3–3 μg/ml) on basal and ADP (3 μM)-induced CD62P externalization were measured in n=62 healthy blood donors and n=177 patients with stable coronary artery disease. All subjects were genotyped for the human platelet antigen-1 (HPA-1, Pl A) polymorphism by GALIOS® and fluorescence correlation spectroscopy. Although a significant platelet hyperreactivity was observed in the patients, the HPA-1 genotype did not influence basal or ADP-induced CD62P expression. A moderate (twofold) stimulation of CD62P expression by abciximab but not by tirofiban or eptifibatide was observed in one patient. Interestingly, this patient carried the HPA-1 b/b genotype. In no other subject any activation of platelets by GP IIb/IIIa inhibitors was observed and there were no statistically significant differences between HPA-1 genotypes with respect to the effects of GP IIb/IIIa inhibitors on basal or ADP-stimulated CD62P expression. It is concluded that paradoxical platelet activation by abciximab is a rare (