Interplay of platelet polymorphisms, risk factors, and von [corrected] Willebrand factor [corrected] in determining collagen-adenosine diphosphate PFA-100 results in patients with coronary artery disease.
Platelets play a pivotal role in thrombus formation in patients with coronary artery disease (CAD), since the high shear generated in the presence of severe coronary stenoses can increase platelet reactivity (PR) and trigger thrombogenesis. Several reports have suggested a functional effect of human platelet antigen (HPA)-1 and HPA-2 gene polymorphisms on PR. However, the true determinants of high-shear PR in CAD patients taking their usual medications are still incompletely understood. In 104 patients with stable CAD we analyzed the possible clinical, biochemical and genetic factors affecting high-shear PR, measured by the ex vivo platelet function analyzer (PFA-100) collagen-adenosine diphosphate method. In univariate analysis, a lower PR was associated with decreased plasma von Willebrand factor-ristocetin cofactor activity, increased blood levels of triglycerides, female sex, use of thienopyridines, lower platelet count, and HPA-1b carriership. All variables, except HPA-1b, remained associated with lower PR in multivariate analysis. However, the introduction in the model of the HPA-1 and HPA-2 genotypes as interaction terms led to a significant improvement in the prediction of PR, although the quantitative effect was small (about 3% improvement, P=0.046).Thus, in CAD patients, there seems to be only a mild effect of the platelet glycoprotein HPA-1 and HPA-2 polymorphisms on collagen-adenosine diphosphate-stimulated PR after the effect of well-established clinical and biochemical determinants are considered.
Porto
Italo
I
Department of Cardiology, John Radcliffe Hospital, Oxford, UK. i.porto@doctors.org.uk
Leone
Antonio Maria
AM
Nanni
Luisa
L
Sciahbasi
Alessandro
A
De Vita
Maria
M
Lanza
Gaetano Antonio
GA
Andreotti
Felicita
F
D000244:Adenosine Diphosphate / Q000032:analysis; D000368:Aged; D000941:Antigens / Q000097:blood*; D016824:Antigens, Human Platelet / Q000235:genetics*; D003094:Collagen / Q000032:analysis; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D010925:Placental Function Tests; D015539:Platelet Activation / Q000235:genetics; D011379:Prognosis; D012310:Ristocetin / Q000097:blood*; D014841:von Willebrand Factor / Q000276:immunology
D000941:Antigens; D016824:Antigens, Human Platelet; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D012310:Ristocetin; D000244:Adenosine Diphosphate; D003094:Collagen