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 microg/ml), tirofiban (3-30 nM), or eptifibatide (0.3-3 microg/ml) on basal and ADP (3 microM)-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(R) 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 (<2%) phenomenon. HPA-1 b/b genotype might be a contributing factor but clearly does not predict platelet activation by GP IIb/IIIa inhibitors.
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GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-N CHEMICAL GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N
GP IIb/IIIa CD62P HPA-1 GP IIb/IIIa GPIIb/IIIa HPA-1 Pl(A) CD62P human platelet antigen-1 human platelet antigen-1 ADP HPA-1 Pl(A) HPA-1 CD62P CD62P HPA-1 glycoprotein IIb/IIIa tirofiban eptifibatide ADP ADP tirofiban eptifibatide GP IIb/IIIa HPA-1