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

K. E. Aspry, T. Paglieroni, R. Gosselin, C. T. Kappagoda, Theodore Wun

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Feb 1999

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Estrogen Replacement Therapy
Hormone Replacement Therapy
Platelet Activation
Platelets
Agglomeration
Chemical activation
Hormones
Blood Platelets
Epinephrine
Adenosine Diphosphate
Estrogens
Collagen
Blood
Ristocetin
P-Selectin
Progestins
Flow cytometry
Platelet Aggregation
Arachidonic Acid
Thrombin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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Effects of post-menopausal hormone replacement therapy on ex-vivo platelet activation & aggregation. / Aspry, K. E.; Paglieroni, T.; Gosselin, R.; Kappagoda, C. T.; Wun, Theodore.

In: Journal of Investigative Medicine, Vol. 47, No. 2, 02.1999.

Research output: Contribution to journalArticle

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abstract = "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{\circledR} (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.",
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AU - Wun, Theodore

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N2 - 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.

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