Evaluation of an antibody-based genotype classification of the platelet fibrinogen receptor (GPIIb/IIIa)

Abstract

Platelet membrane glycoprotein (GP) IIb/IIIa is the central molecule in platelet adhesion and aggregation by high-affinity binding of fibrinogen. Polymorphism of the beta chain of the receptor, especially the GPIIIa-proline33 allele [HPA-1b, Zwb, PI(A2)], has been suggested to be associated with a variety of vascular diseases, such as coronary stenosis, myocardial infarction, cerebral ischemia, or venous thrombosis. Using clinical chemistry standards, we evaluate a flow cytometric whole-blood, antibody-based method to determine the genotype [PI(A1A1), PI(A1A2), PI(A2A)] versus polymerase chain reaction (PCR)-based DNA restriction fragment length analysis in 220 individuals. Both homozygous and heterozygous genotypes differ in the expression of binding sites for the monoclonal antibody, SZ21. Agreement between the two methods was achieved in 187 cases, which reflects a test validity of 85%, a sensitivity of 83.6%, and a specificity of 85.4%. We conclude that flow cytometry is reliable for classifying the PI(AX) genotype. The performance characteristics are easy, fast, and cheap (genomics by proteomics). These features make it suitable for screening patients and broad populations for the future risk of cardiovascular ischemic events. © 2001 Wiley-Liss, Inc.