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Thromb Haemost 1997; 77(04): 748-754
DOI: 10.1055/s-0038-1656045
Platelets
Schattauer GmbH Stuttgart

Gender Differences in Platelet GPIIb-IIIa Activation

Nauder Faraday
The Divisions of Hematology and Cardiology, and Departments of Medicine and Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
,
Pascal J Goldschmidt-Clermont
The Divisions of Hematology and Cardiology, and Departments of Medicine and Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
,
Paul F Bray
The Divisions of Hematology and Cardiology, and Departments of Medicine and Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Publication History

Received 03 October 1994

Accepted after resubmission 04 November 1996

Publication Date:
11 July 2018 (online)

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Summary

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 10-7M), however, the number of GPIIb-IIIa receptors per platelet capable of binding fibrinogen was significantly greater in women than men in response to 20μM ADP (16,319 ± 1871 vs 9669±1994, p = 0.02), 20μM ADP (39,951 ± 4711 vs 25,948 ± 4953, p = 0.05) and 50μM 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.

 

  • References

  • 1 Puletti M, Sunseri L, Curione M, ErbaS M, Borgia C. Acute myocardial infarction: sex-related differences in prognosis. Am Heart J 1984; 108: 63-66
    CrossrefPubMedGoogle Scholar
  • 2 Greenland P, Reicher-Reiss H, Goldbourt U, Behar S. In-hospital and 1-year mortality in 1,524 women after myocardial infarction Comparison with 4,315 men [see comments]. Circulation 1991; 83: 484-491
    CrossrefPubMedGoogle Scholar
  • 3 Loop FD, Golding LR, MacMillan JP, Cosgrove DM, Lytle BW, Sheldon WC. Coronary artery surgery in women compared with men: analyses of risks and long-term results. J Am Coll Cardiol 1983; 1: 383-390
    CrossrefPubMedGoogle Scholar
  • 4 Letsky E, de SwietM. Annotation. Thromboembolism in pregnancy and its management. [Review]. Br J Haematol 1984; 57: 543-552
    CrossrefPubMedGoogle Scholar
  • 5 Stadel BV. Oral contraceptives and cardiovascular disease (first of two parts). [Review]. N Engl J Med 1981; 305: 612-618
    CrossrefPubMedGoogle Scholar
  • 6 Stadel BV. Oral contraceptives and cardiovascular disease (second of two parts). [Review]. N Engl J Med 1981; 305: 672-677
    CrossrefPubMedGoogle Scholar
  • 7 Harris WH, Salzman EW, Athanasoulis CA, Waltman AC, DeSanctis RW. Aspirin prophylaxis of venous thromboembolism after total hip replacement. N Engl J Med 1977; 297: 1246-1249
    CrossrefPubMedGoogle Scholar
  • 8 The Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med 1978; 299: 53-59
    CrossrefPubMed
  • 9 Fitzgerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary disease. N Engl J Med 1986; 315: 983-989
    CrossrefPubMedGoogle Scholar
  • 10 Socol ML, Weiner CP, Louis G, Rehnberg K, Rossi EC. Platelet activation in preeclampsia. Am J Obstet Gynecol 1985; 151: 494-497
    CrossrefPubMedGoogle Scholar
  • 11 Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature 1975; 253: 355-357
    CrossrefPubMedGoogle Scholar
  • 12 Zahavi J, Dreyfuss F, Kalef M, Soferman N. Adenosine diphosphate-induced platelet aggregation in healthy women with and without a combined and sequential contraceptive pill. Am J Obstet Gynecol 1973; 117: 107-113
    CrossrefPubMedGoogle Scholar
  • 13 Yamazaki H, Motomiya T, Kikutani N, Sakakibara C, Watanabe S, Numata M, Noguchi K. Platelet aggregation during menstrual cycle and pregnancy. Thromb Res 1979; 14: 333-340
    CrossrefPubMedGoogle Scholar
  • 14 Kelton JG, Powers P, Julian J, Boland V, Carter CJ, Gent M, Hirsh J. Sex-related differences in platelet aggregation: influence of the hematocrit. Blood 1980; 56: 38-41
    PubMedGoogle Scholar
  • 15 Shattil SJ, Hoxie JA, Cunningham M, Brass LF. Changes in the platelet membrane glycoprotein Ilb/IIIa complex during platelet activation. J Biol Chem 1985; 260: 11107-11114
    PubMedGoogle Scholar
  • 16 Faraday N, Goldschmidt-Clermont P, Dise K, Bray PF. Quantitation of soluble fibrinogen binding to platelets by fluorescence-activated flow cytometry. J Lab Clin Med 1994; 123: 728-740
    PubMedGoogle Scholar
  • 17 Finkel T, Theriot JA, Dise KR, Tomaselli GF. Goldschmidt-Clermont PJ. Dynamic actin structures stabilized by profilin. Proc Natl Acad Sci USA 1994; 91: 1510-1514
    CrossrefPubMedGoogle Scholar
  • 18 Klotz IM. Numbers of receptor sites from Scatchard graphs: facts and fantasies. Science 1982; 217: 1247-1249
    CrossrefPubMedGoogle Scholar
  • 19 Vassallo Jr R, Kieber-Emmons T, Cichowski K, Brass LF. Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides. J Biol Chem 1992; 267: 6081-6085
    PubMedGoogle Scholar
  • 20 McGregor JL, Brochier J, Wild F, Follea G, Trzeciak MC, James E, Decha-vanne M, McGregor L, Clemetson KJ. Monoclonal antibodies against platelet membrane glycoproteins. Characterization and effect on platelet function. Eur J Biochem 1983; 131: 427-436
    CrossrefPubMedGoogle Scholar
  • 21 Peerschke El, Coller BS. A murine monoclonal antibody that blocks fibrinogen binding to normal platelets also inhibits fibrinogen interactions with chymotrypsin-treated platelets. Blood 1984; 64: 59-63
    PubMedGoogle Scholar
  • 22 Marguerie GA, Edgington TS, Plow EF. Interaction of fibrinogen with its platelet receptor as part of a multistep reaction in ADP-induced platelet aggregation. J Biol Chem 1980; 255: 154-161
    PubMedGoogle Scholar
  • 23 Plow EF, Marguerie GA. Induction of the fibrinogen receptor on human platelets by epinephrine and the combination of epinephrine and ADP. J Biol Chem 1980; 255: 10971-10977
    PubMedGoogle Scholar
  • 24 Niiya K, Hodson E, Bader R, Byers-Ward V, Koziol JA, Plow EF, Ruggeri ZM. Increased surface expression of the membrane glycoprotein Ilb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation. Blood 1987; 70: 475-483
    PubMedGoogle Scholar
  • 25 Elkeles RS, Hampton JR, Mitchell JR. Effect of oestrogens on human platelet behaviour. Lancet 1968; 2: 315-318
    PubMedGoogle Scholar
  • 26 Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, Albelda SM, Buck CA. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest 1992; 90: 188-195
    CrossrefPubMedGoogle Scholar
  • 27 Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin alpha 2 beta 1 activity on human platelets. Blood 1993; 82: 2693-2703
    PubMedGoogle Scholar
  • 28 Goldschmidt-Clermont P, Schulman S, Bray P, Chandra N, Khan F, Grigoryev D, Kitt M, Gottdiener P, Gerstenblith G. Refining the treatment for women with unstable angina. Clin Card 1996; 19: 869-874
    PubMedGoogle Scholar