Increased platelet reactivity due to platelet receptor polymorphisms? Not in the real world.

Receptor Polymporphisms? Not in the Real World To the Editor: We read with interest the article by Pontiggia et al,1 discussing the possible functional implications of double homozygosity for two “prothrombothic” platelet glycoprotein receptor polymorphisms (Pl of GpIIIa and C807T of GpIa) in a family with a strong history of premature cardiovascular events. We would like to report our experience in 90 stable coronary artery disease (CAD) patients, studied in the “real world” while taking their usual medications, in whom we tried to recognize environmental and genetic determinants of high-shear platelet aggregation, measured by collagen-ADP PFA100 closure time (mimicking the high-shear conditions of diseased arteries). Using a multivariate analysis approach, we recorded clinical variables such as age, sex, smoking, diabetes, previous myocardial infarction, and drug therapy, including use of thyenopiridines (aspirin use was not considered as it is known not to influence collagenADP PFA-100 values). We also measured laboratory variables (platelet and white blood cell count, mean platelet volume, cholesterol, triglycerides, von Willebrand factor activity as Ristocetin Cofactor Activity [vWf RCA]) and determined GpIIIa Pl and GpIa C807T genotypes. On univariate analysis, increased vWf RCA (r 0.372, P 0.0001) and platelet count (r 0.207, P 0.04), reduced triglyceride levels (r 0.318, P 0.002), male sex (89 18 vs 105 23 s, P 0.003) and nonusage of thyenopiridines (84 16 vs 96 20 s, P 0.02) were associated with increased platelet reactivity (ie, reduced PFA-100 closure times). In contrast, the genetic polymorphisms were not. No double homozygotes for the variant genotypes were observed in our population, and double heterozygotes did not differ from the general population (Table). On stepwise multivariate linear regression, all the nongenetic predictors maintained their significant relation with closure time (with vWf RCA remaining the strongest predictor), with an R (total explained variance) of 0.52, indicating a good predictive power. When the genetic predictors were forced into the model, no significant increase in the explained variance occurred. Thus, in a general population of patients with stable CAD taking their usual medications, the presence of putative “prothrombotic” GpIa and GpIIIa polymorphisms is unlikely to exert important effects on platelet reactivity. We believe the results by Pontiggia et al1 are very convincing. However, the authors do not claim universal applicability of their findings. Moreover, some old-fashioned predictors of platelet reactivity, such as platelet count, were not considered in their analysis, because these authors correctly used platelet-rich plasma (at a fixed concentration) for their functional tests and for PFA-100 closure times.