Increased binding of fibrinogen to glycoprotein IIIa-proline33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease.
OBJECTIVE
The GPIIb-IIIa complex on the platelet membrane plays an important part in thrombosis as it is the receptor for fibrinogen. The gene for platelet membrane glyco-protein IIIa has multiple alleles one of which, the GPIIIa-Proline33 (HPA-1b, PlA2, Zwb) allele has been reported in some, but not all studies, to be associated with an increased risk of myocardial infarction. We investigated whether the presence of the Pro33 form of GPIIIa on the platelet membrane is associated with increased fibrinogen binding.


RESULTS
Blood samples from 70 patients (54 male) with stable angina of whom 22 (18 male) had a history of previous myocardial infarction, were analysed for the GPIIIa-Leu-Pro33 polymorphism at the genomic level, and for whole blood flow cytometric measurement of platelet fibrinogen binding. The GPIIIa-Pro33 form was present in 20 (28.6%) patients (1 homozygous) representing an allele frequency of 0.85 and 0.15 (GPIIIa-Leu33:Pro33). The incidence of myocardial infarction was higher (40.0%) in patients positive for GPIIIa-Pro33 than in those without (32.0%) but this was not significant (P=0.58). Fibrinogen binding to ADP-stimulated platelets was significantly higher in the GPIIIa-Pro33 positive group at all ADP concentrations (<0.0001; two way ANOVA). There was no association between fibrinogen binding and the level of expression of the GPIIb-IIIa complex, platelet volume or platelet count. Fibrinogen binding in response to thrombin stimulation was not different between the groups (P>0.05).


CONCLUSIONS
The increased tendency of platelets from patients with the Pro33 form of GPIIIa may predispose patients with this allele to a higher risk of acute thrombotic events, and argues for selective use of therapeutic agents that inhibit ADP-mediated platelet activation in occlusive vascular disease states.
D000368:Aged; D000483:Alleles; D000787:Angina Pectoris / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D011485:Protein Binding