Effects of post-menopausal hormone replacement therapy on ex-vivo platelet activation & aggregation

BACKGROUND: Hormone replacement therapy (HRT) has been associated with an increased risk of venous thrombosis, but effects on platelet function are unknown. OBJECTIVE: To measure the effects of HRT on ex-vivo platelet activation (Plt Act) and aggregation (Plt Ag) using available methods in parallel. METHODS: Women (n=16, x̄ age=57 yrs) on HRT (estrogen 0.625-1.25 mg ± a progestin) for ≥6 mos underwent platelet testing on HRT, then re-testing after 8-12 wks off HRT. Plt Act (basal, +ADP 100um, +Epinephrine 500um [Epi]) was measured in whole blood via flow cytometry using monoclonal antibodies to the activation-dependent marker P-selectin (CD62). Plt Ag and ATP release in response to collagen and other agonists was measured via whole blood lumiaggregometry (L-A), and via the Platelet Function Analyzer® (PFA). Results were analyzed using non-parametric methods. RESULTS: On HRT, ex vivo platelets demonstrated a significant increase in CD62 expression in response to Epi: median 6.3% (range 2.6-21.9%) vs. 5.0% (range 1.5-13.1%) (p=.02, Wilcoxon). Three of four with the highest Epi-stimulated CD62 expression were taking the highest estrogen doses. No differences were observed in basal or ADP-stimulated CD62 expression, in L-A in response to collagen, arachidonic acid, ristocetin or thrombin, or in PFA closure times. CONCLUSIONS: These data suggest that HRT may result in increased platelet reactivity to the physiological agonist epinephrine, possibly contributing to a pro-thrombotic state.