Estradiol increases platelet aggregation in PlA1/A1 individuals

Background The platelet glycoprotein IIb/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 PlA1/A1 and 15 PlA1/A2) before and after incubation with β-estradiol (E2) (10−11 mol/L). The effect of E2 10−11 mol/L on PlA1/A1 platelets demonstrated a significant increase (P = .03) in aggregation compared with baseline. In contrast, with the same concentration of E2, aggregation of PlA1/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 PlA1/A1 individuals, but not in PlA1/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.