Reduced inhibition by abciximab in platelets with the PlA2 polymorphism.
BACKGROUND
The PlA2 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 PlA1/A2 patients undergoing percutaneous coronary interventions. The affinity of abciximab for the PlA1 and PlA2 receptors was determined with use of transfected cells.


RESULTS
Compared with PlA1/A1 homozygotes, PlA1/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 Pl(A1/A2) platelets were less completely inhibited after abciximab bolus (P =.05). The radiometric abciximab binding assay demonstrated that the PlA1/A2 platelets had fewer baseline fibrinogen receptors than did the PlA1/A1 platelets (P =.04) and more free fibrinogen receptors at 24 hours (P =.008). Cells transfected to express homozygous PlA1 or PlA2 demonstrated a nonsignificant trend (P =.12) for reduced abciximab affinity for PlA2.


CONCLUSIONS
PlA1/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 PlA2-positive platelets may contribute to a less favorable outcome in these patients.
Wheeler
Guy L
GL
Section of Cardiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1045, USA.
Braden
Gregory A
GA
Bray
Paul F
PF
Marciniak
Stanley J
SJ
Mascelli
Mary Ann
MA
Sane
David C
DC
D000077284:Abciximab; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D016824:Antigens, Human Platelet / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism* / Q000627:therapeutic use; D039661:Integrin beta3; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011110:Polymorphism, Genetic; D014162:Transfection
D000911:Antibodies, Monoclonal; D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D007140:Immunoglobulin Fab Fragments; D039661:Integrin beta3; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077284:Abciximab