Ah. Goodall et al., Increased binding of fibrinogen to glycoprotein IIIa-Proline33 (HPA-1b, Pl(A2), Zw(b)) positive platelets in patients with cardiovascular disease, EUR HEART J, 20(10), 1999, pp. 742-747
Aims The GPIIb-IIIa complex on the platelet membrane plays an important par
t in thrombosis as it is the receptor for fibrinogen. The gene for platelet
membrane glycoprotein IIIa has multiple alleles one of which, the GPIIIa-P
roline33 (HPA-1b, pl(A2), ZW(b)) allele has been reported in some, but not
all studies, to be associated with an increased risk of myocardial infarcti
on. We investigated whether the presence of the Pro33 form of GPIIIa on the
platelet membrane is associated with increased fibrinogen binding.
Methods and Results Blood samples from 70 patients (54 male) with stable an
gina of whom 22 (18 male) had a history of previous myocardial infarction,
were analysed for the GPIIIa-Leu-Pro33 polymorphism at the genomic level, a
nd for whole blood flow cytometric measurement of platelet fibrinogen bindi
ng. 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). Th
e incidence of myocardial infarction was higher (40.0%) in patients positiv
e for GPIIIa-Pro33 than in those without (32.0%) but this was not significa
nt (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 b
etween the groups (p>0.05).
Conclusions The increased tendency of platelets from patients with the Pro3
3 form of GPIIIa may predispose patients with this allele to a higher risk
of acute thrombotic events, and argues for selective use of therapeutic age
nts that inhibit ADP-mediated platelet activation in occlusive vascular dis
ease states.