Gender differences in platelet GPIIb-IIIa activation

Nauder Faraday, Pascal Goldschmidt-Clermont, Paul F. Bray

Research output: Contribution to journalArticle

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Abstract

Gender differences in the development of thrombotic diseases have been described in numerous clinical settings. Enhanced platelet reactivity in both sexes is associated with the development of vascular thromboses. Because activation of platelet GPIIb-IIIa receptors is a central event in thrombus formation, we examined GPIIb-IIIa function in normal male and female volunteers. Using flow cytometry, we quantitated gender differences in the number of binding sites for FITC-labeled fibrinogen (FITC-FGN) and FITC-labeled PAC-1 antibody (FITC-PAC-1). Washed platelets were incubated with either FITC-FGN or FITC-PAC-1 and activated with either ADP or thrombin receptor activating peptide (TRAP) prior to cytometric acquisition of data. The dissociation constant for FITC-FGN was the same in both sexes (approx. 1.6 x 10-7 M), however, the number of GPIIb-IIIa receptors per platelet capable of binding fibrinogen was significantly greater in women than men in response to 2 μM ADP (16,319 ± 1871 vs 9669 ± 1994, p = 0.02), 20 μM ADP (39,951 ± 4711 vs 25,948 ± 4953, p = 0.05) and 50 μM TRAP (39,236 ± 3965 vs 21,848 ± 4159, p = 0.007). Similarly, the number of GPIIb-IIIa receptors capable of binding PAC-1 in response to ADP and TRAP was 50% to 80% greater in women than men. Binding experiments using specific anti-GPIIb-IIIa monoclonal antibodies (P2 and 10E5), as well as quantitative Western blotting experiments, showed no gender difference in the total number of GPIIb-IIIa molecules expressed. Analysis of data from female subgroups demonstrated an association of GPIIb-IIIa reactivity with menstrual phase. We conclude that GPIIb-IIIa receptors on platelets from premenopausal women are more 'activatable' than those on platelets from young men. Variations in the serum concentrations of estrogens and/or progestins may modulate GPIIb-IIIa function.

Original languageEnglish
Pages (from-to)748-754
Number of pages7
JournalThrombosis and Haemostasis
Volume77
Issue number4
StatePublished - Apr 1 1997
Externally publishedYes

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thrombin receptor peptide SFLLRNP
Fluorescein-5-isothiocyanate
Platelet Glycoprotein GPIIb-IIIa Complex
Blood Platelets
Adenosine Diphosphate
Fibrinogen
Thrombosis
Antibodies
Platelet Activation
Progestins
Blood Vessels
Volunteers
Flow Cytometry
Estrogens
Western Blotting
Binding Sites
Monoclonal Antibodies
Serum
2-carboxyarabinitol 1-phosphate

ASJC Scopus subject areas

  • Hematology

Cite this

Faraday, N., Goldschmidt-Clermont, P., & Bray, P. F. (1997). Gender differences in platelet GPIIb-IIIa activation. Thrombosis and Haemostasis, 77(4), 748-754.

Gender differences in platelet GPIIb-IIIa activation. / Faraday, Nauder; Goldschmidt-Clermont, Pascal; Bray, Paul F.

In: Thrombosis and Haemostasis, Vol. 77, No. 4, 01.04.1997, p. 748-754.

Research output: Contribution to journalArticle

Faraday, N, Goldschmidt-Clermont, P & Bray, PF 1997, 'Gender differences in platelet GPIIb-IIIa activation', Thrombosis and Haemostasis, vol. 77, no. 4, pp. 748-754.
Faraday N, Goldschmidt-Clermont P, Bray PF. Gender differences in platelet GPIIb-IIIa activation. Thrombosis and Haemostasis. 1997 Apr 1;77(4):748-754.
Faraday, Nauder ; Goldschmidt-Clermont, Pascal ; Bray, Paul F. / Gender differences in platelet GPIIb-IIIa activation. In: Thrombosis and Haemostasis. 1997 ; Vol. 77, No. 4. pp. 748-754.
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