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Reduced inhibition by abciximab in platelets with the PlA2 polymorphism
Guy L Wheeler1, Gregory A Braden, Paul F Bray
1Section of Cardiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1045, USA.
American Heart Journal
|January 5, 2002
Summary
Platelets with the PlA2 polymorphism show reduced inhibition by abciximab, a glycoprotein IIb/IIIa inhibitor. This altered platelet function may increase the risk of adverse events after percutaneous coronary intervention.
Area of Science:
- Cardiovascular Medicine
- Pharmacogenomics
- Platelet Biology
Background:
- The PlA2 polymorphism in the glycoprotein IIb/IIIa receptor is linked to higher rates of restenosis and stent thrombosis.
- This genetic variation may influence the effectiveness of antiplatelet drugs like abciximab.
Purpose of the Study:
- To investigate whether the PlA2 polymorphism affects abciximab's antiplatelet activity in patients undergoing percutaneous coronary intervention (PCI).
Main Methods:
- Evaluated platelet aggregation and function using optical and rapid assays in patients with PlA1/A1 and PlA1/A2 genotypes.
- Assessed abciximab binding to platelets and its affinity for PlA1 and PlA2 receptors using radiometric assays and transfected cells.
Main Results:
- PlA1/A2 platelets exhibited significantly less inhibition by abciximab compared to PlA1/A1 platelets post-bolus and at 24 hours.
- Fewer baseline fibrinogen receptors and more free receptors at 24 hours were observed on PlA1/A2 platelets.
- A trend towards reduced abciximab affinity for the PlA2 receptor was noted.
Conclusions:
- PlA1/A2 platelets demonstrate incomplete inhibition by abciximab, contributing to variable antiplatelet responses.
- The reduced effectiveness of abciximab in PlA2-positive individuals may explain poorer clinical outcomes after PCI.