In vivo platelet activation in atherothrombotic stroke is not determined by polymorphisms of human platelet glycoprotein IIIa or Ib

Platelet membrane glycoprotein polymorphisms are candidate risk factors for thrombosis, but epidemiological data are conflicting. Thus, demonstration of a genotype-dependent alteration in function is desirable to resolve thes e inconsistencies. We investigated in vivo platelet activation in acute thr ombosis and related this to platelet genotype. Frequencies of the 1b and 2b alleles of the HPA 1a/1b and HPA 2a/2b platelet glycoprotein polymorphisms were determined in 150 (52 men/98 women, mean age 58.3 years) patients wit h atherothrombotic stroke, and the influence of genotype on markers of plat elet activation was assessed, Platelet P-selectin (CD62P) expression and fi brinogen binding was measured using whole blood flow cytometry within 24 h of stroke and 3 months later in 77 patients who provided a repeat blood sam ple. Results were compared with matched controls, Neither the Ib allele [al lele frequency 0.11 vs. 0.13, odds ratio (OR) confidence interval (CI) 0.8 (0.5-1.3)] nor the 2b allele [0.09 vs. 0.07, OR (CI) 1.4 (0.8-2.4)] was sig nificantly over-represented in patients. Increased numbers of activated pla telets were found following stroke (acute mean P-selectin expression 0.64% vs. control 0.35%, P <0.001; acute mean fibrinogen binding 1.6% vs. control 0.9%, P < 0.001). Activation persisted in the convalescent phase (P < 0.00 1 and P = 0.005 vs. controls for P-selectin and fibrinogen respectively). E xpression of P-selectin and fibrinogen was not influenced by either the HPA 1a/1b genotype (P > 0.95 for each marker, Scheffe's test) or the 2a/2b gen otype (P > 0.95 for each). Although persisting platelet activation is seen in atherothrombotic stroke, it is independent of HPA 1a/1b and 2a/2b genoty pes. These data suggest an underlying prothrombotic state, but do not suppo rt the polymorphisms studied as risk factors for thrombotic stroke in this population.