Reduced inhibition by abciximab in platelets with the PIA2 polymorphism

Background The Pl(A2) polymorphism of the glycoprotein IIb/IIIa (fibrinogen) receptor has been associated with increased restenosis and stent thrombosis. We postulated that this allele could alter the antiplatelet effect of abciximab in patients undergoing percutaneous coronary intervention. Methods Optical platelet aggregation assays, Ultegra (Accumetrics, San Diego) rapid platelet function assays, and radiometric abciximab binding assays were performed in 66 pl(A1)/(A1) and 21 pl(Al)/(A2) patients undergoing percutaneous coronary interventions. The affinity of abciximab for the pl(A1) and Pl(A2) receptors was determined with use of transfected cells. Results Compared with pl(A1)/(A1) homozygotes, pl(A1/A2) platelets were less completely inhibited after abciximab bolus (P =.002) and at 24 hours (P =.02) as assessed by the rapid platelet function assays. Optical aggregation assays confirmed that plAl/A2 platelets were less completely inhibited after abciximab bolus (P =.05). The radiometric abciximab binding assay demonstrated that the pl(A1/A2) platelets had fewer baseline fibrinogen receptors than did the pl(A1/A1) platelets (P = .04) and more free fibrinogen receptors at 2.4 hours (P = .008). Cells transfected to express homozygous pl(A1) or pl(A2) demonstrated a nonsignificant trend (P = .12) for reduced abciximab affinity for pl(A2). Conclusions pl(A1/A2) platelets are less completely inhibited with abciximab, contributing to the observed interindividual variability in platelet function inhibition. Because the extent of platelet inhibition is an independent predictor for the risk of major adverse coronary events after percutaneous coronary intervention, the relative resistance of pl(A2)-positive platelets may contribute to a less favorable outcome in these patients.