Estradiol increases platelet aggregation in PlA1/A1 individuals

Background The platelet glycoprotein Ilb/IIIa receptor is a key mediator of platelet aggregation and intracoronary thrombosis. Studies have suggested that hormone replacement therapy (HRT) may increase coronary events in postmenopausal women. Objectives We sought to characterize the relationship between the estrogen concentration expected in HRT and platelet aggregation. Design and Results Platelet aggregation studies were performed using epinephrine on 30 healthy individuals (15 pI(A1/A1) and 15 pI(A1/A2)) before and after incubation with beta-estradiol (E-2) (10(-11) mol/L). The effect of E-2 10(-11) mol/L on Pi(A1/A1) platelets demonstrated a significant increase (P =.03) in aggregation compared with baseline. In contrast, with the same concentration of E2, aggregation of pI(A1/A2) platelets decreased significantly compared with baseline (P <.0001). Conclusions Estrogen concentration similar to that expected in HRT resulted in an increase in platelet aggregation in pl(A1/A1) individuals, but not in pl(A1/A2) individuals. The data may provide further insight for the increase in coronary events seen in HRT clinical trials and suggest that further evaluation is needed to better define the role of pharmacogenetics in HRT.