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Thromb Haemost 1998; 80(04): 588-591
DOI: 10.1055/s-0037-1615426
Rapid Communication
Schattauer GmbH

Plasma Levels of Activated Factor VII Decrease during the Menstrual Cycle

Stylianos Kapiotis
1   From the Department of Clinical Pharmacology-TARGET, Vienna, Austria
2   From the Clinical Institute of Medical and Chemical Laboratory Diagnostics, General Hospital Vienna, University of Vienna, Vienna, Austria
,
Bernd Jilma
1   From the Department of Clinical Pharmacology-TARGET, Vienna, Austria
,
Thomas Pernerstorfer
1   From the Department of Clinical Pharmacology-TARGET, Vienna, Austria
,
Petra Stohlawetz
1   From the Department of Clinical Pharmacology-TARGET, Vienna, Austria
,
Hans-Georg Eichler
1   From the Department of Clinical Pharmacology-TARGET, Vienna, Austria
,
Wolfgang Speiser
2   From the Clinical Institute of Medical and Chemical Laboratory Diagnostics, General Hospital Vienna, University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received 07 April 1998

Accepted after resubmission 22 June 1998

Publication Date:
08 December 2017 (online)

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Summary

Men have an increased cardiovascular risk as compared to women, which is largely ascribed to the cardioprotective effects of female sex steroids. We hypothesised that this may be reflected by differences in the activation status of the coagulation system. Hence the aim of this study was to compare plasma levels of activated factor VII (FVIIa) in men and women, and to study the influence of the menstrual cycle on FVIIa levels.

In a prospective study we investigated 20 healthy young women and 20 men. Men had significantly higher levels of activated factor VII (60 mU/ml, CI: 52 to 67) than women during all phases of the menstrual cycle. In women FVIIa was higher during the follicular phase (41 mU/ml, CI: 33 to 50) than during midcycle (34 mU/ml, CI: 24 to 45; p = 0.022 vs. follicular phase) and during the luteal phase (33 mU/ml, CI: 24 to 42; p = 0.006 vs. follicular phase). Prothrombin fragment (F1 + 2) levels decreased from 0.86 nmol/l (CI: 0.51-1.21) by -23% (-39% to -8%; p = 0.011) during midcycle and by -25% (CI: -51% to 1%; p = 0.023) during the luteal phase.

These data support the contention that plasma levels of FVIIa, a key enzyme of the coagulation cascade, may be down-regulated by endogenously produced female sex hormones during the menstrual cycle. This may at least partially explain the marked gender differences found in FVIIa.

 

  • References

  • 1 Stampfer MJ, Willett WC, Colditz GA, Rosner B, Speizer FE, Hennekens CH. A prospective study of postmenopausal estrogen therapy and coronary heart disease.. N Engl J Med 1985; 313: 1044-9.
    CrossrefPubMedGoogle Scholar
  • 2 Sullivan JM, Vander Zwaag R, Lemp GF, Hughes JP, Maddock V, Kroetz FW, Ramanathan KB, Mirvis DM. Postmenopausal estrogen use and coronary atherosclerosis.. Ann Intern Med 1988; 108: 358-63.
    CrossrefPubMedGoogle Scholar
  • 3 Bush TL, Cowan LD, Barrett Connor E, Criqui MH, Karon JM, Wallace RB, Tyroler HA, Rifkind BM. Estrogen use and all-cause mortality. Preliminary results from the Lipid Research Clinics Program Follow-up Study.. JAMA 1983; 249: 903-6.
    CrossrefPubMedGoogle Scholar
  • 4 Bush TL, Barrett Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, Tyroler HA, Rifkind BM. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study.. Circulation 1987; 75: 1102-9.
    CrossrefPubMedGoogle Scholar
  • 5 Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study.. Lancet 1993; 342: 1076-9.
    CrossrefPubMedGoogle Scholar
  • 6 Gebara OC, Mittleman MA, Sutherland P, Lipinska I, Matheney T, Xu P, Welty FK, Wilson PW, Levy D, Muller JE. et al. Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study.. Circulation 1995; 91: 1952-8.
    CrossrefPubMedGoogle Scholar
  • 7 Miller GJ, Wilkes HC, Meade TW, Bauer KA, Barzegar S, Rosenberg RD. Haemostatic changes that constitute the hypercoagulable state.. Lancet 1991; 338: 1079.
    PubMedGoogle Scholar
  • 8 Kario K, Miyata T, Sakata T, Matsuo T, Kato H. Fluorogenic assay of activated factor VII. Plasma factor VIIa levels in relation to arterial cardiovascular diseases in Japanese.. Arterioscler Thromb 1994; 14: 265-74.
    CrossrefPubMedGoogle Scholar
  • 9 Kario K, Matsuo T, Kobayashi H, Matsuo M, Sakata T, Miyata T. Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria.. Arterioscler Thromb Vasc Biol 1995; 15: 1114-20.
    CrossrefPubMedGoogle Scholar
  • 10 Miller GJ, Bauer KA, Barzegar S, Cooper JA, Rosenberg RD. Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease.. Thromb Haemost 1996; 75: 767-71.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Scarabin PY, Vissac AM, Kirzin JM, Bourgeat P, Amiral J, Agher R, Guize L. Population correlates of coagulation factor VII. Importance of age, sex, and menopausal status as determinants of activated factor VII.. Arterioscl Thromb Vasc Biol 1996; 16: 1170-6.
    CrossrefPubMedGoogle Scholar
  • 12 Meade TW, North WR, Chakrabarti R, Stirling Y, Haines AP, Thompson SG, Brozovic M. Haemostatic function and cardiovascular death: early results of a prospective study.. Lancet 1980; 1: 1050-4.
    PubMedGoogle Scholar
  • 13 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WR, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.. Lancet 1986; 2: 533-7.
    PubMedGoogle Scholar
  • 14 Albrecht S, Kotzsch M, Siegert G, Luther T, Grossmann H, Grosser M, Muller M. Detection of circulating tissue factor and factor VII in a normal population.. Thromb Haemost 1996; 75: 772-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Lindoff C, Peterson F, Lecander I, Martinsson G, Astedt B. Transdermal estrogen replacement therapy: beneficial effects on hemostatic risk factors for cardiovascular disease.. Maturitas 1996; 24: 43-50.
    CrossrefPubMedGoogle Scholar
  • 16 Jilma B, Fasching P, Ruthner C, Rumplmayr A, Ruzicka S, Kapiotis S, Wagner OF, Eichler HG. Elevated circulating P-selectin in insulin dependent diabetes mellitus.. Thromb Haemost 1996; 76: 328-32.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Jilma B, Hildebrandt J, Kapiotis S, Wagner OF, Kitzweger E, Mullner C, Monitzer B, Krejcy K, Eichler HG. Effects of estradiol on circulating P-selectin.. J Clin Endocrinol Metab 1996; 81: 2350-5.
    PubMedGoogle Scholar
  • 18 Bourgeat P, Jasmin P, Migaud-Fressart M. et al. Direct measurement of activated F. VII in plasma: development of an original assay.. [Abstract] Thromb Haemost 1995; 73 (06) 1024.
    PubMedGoogle Scholar
  • 19 Kapiotis S, Jilma B, Quehenberger P, Ruzicka K, Handler S, Speiser W. Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex.. Circulation 1997; 96: 19-21.
    CrossrefPubMedGoogle Scholar
  • 20 Kapiotis S, Jilma B, Szalay T, Dirnberger E, Wagner O, Eichler HG, Speiser W. Evidence against an effect of endothelin-1 on blood coagulation, fibrinolysis, and endothelial cell integrity in healthy men.. Arterioscler Thromb Vasc Biol 1997; 17: 2861-7.
    CrossrefPubMedGoogle Scholar
  • 21 Jilma B, Eichler HG, Breiteneder H, Wolzt M, Aringer M, Graninger W, Rohrer C, Veitl M, Wagner OF. Effects of 17 beta-estradiol on circulating adhesion molecules.. J Clin Endocrinol Metab 1994; 79: 1619-24.
    PubMedGoogle Scholar
  • 22 Bremme K, Wramsby H, Andersson O, Wallin M, Blomback M. Do lowered factor VII levels at extremely high endogenous oestradiol levels protect against thrombin formation?. Blood Coagul Fibrinolysis 1994; 5: 205-10.
    CrossrefPubMedGoogle Scholar
  • 23 Sporrong T, Mattsson LA, Samsioe G, Stigendal L, Hellgren M. Haemostatic changes during continuous oestradiol-progestogen treatment of postmenopausal women.. Br J Obstet Gynaecol 1990; 97: 939-44.
    CrossrefPubMedGoogle Scholar
  • 24 Kroon UB, Silfverstolpe G, Tengborn L. The effects of transdermal estradiol and oral conjugated estrogens on haemostasis variables.. Thromb Haemost 1994; 71: 420-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Quehenberger P, Loner U, Kapiotis S, Handler S, Schneider B, Huber J, Speiser W. Increased levels of activated factor VII and decreased plasma protein S activity and circulating thrombomodulin during use of oral contraceptives.. Thromb Haemost 1996; 76: 729-34.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Meade TW, Brozovic M, Chakrabarti R, Howarth DJ, North WRS, Stirling Y. An epidemiological study of the haemostatic and other effects of oral contraceptives.. Br J Haematol 1976; 34: 353-64.
    CrossrefPubMedGoogle Scholar
  • 27 Meade TW, Haines AP, North WR, Chakrabarti R, Howarth DJ, Stirling Y. Haemostatic, lipid, and blood-pressure profiles of women on oral contraceptives containing 50 microgram or 30 microgram oestrogen.. Lancet 1977; 2: 948-51.
    PubMedGoogle Scholar
  • 28 Wright D, Poller L, Thomson JM, Sidebotham A, Hirst CF, Hirsch P. A longitudinal study of the Factor VII rise during pregnancy.. Thromb Haemost 1997; 77: 328-30.
    PubMedGoogle Scholar
  • 29 Aune B, Oian P, Omsjo I, Østerud B. Hormone replacement therapy reduces the reactivity of monocytes and platelets in whole blood – a beneficial effect on atherogenesis and thrombus formation?. Am J Obstet Gynecol 1995; 173: 1816-20.
    CrossrefPubMedGoogle Scholar