Download PDF
Thromb Haemost 1999; 82(03): 1024-1027
DOI: 10.1055/s-0037-1614323
Letters to the Editor
Schattauer GmbH

Venous Thrombosis, Oral Contraceptives and High Factor VIII Levels

K. W. M. Bloemenkamp
1   From the Department of Obstetrics, Gynaecology and Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands
,
F. M. Helmerhorst
1   From the Department of Obstetrics, Gynaecology and Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands
,
F. R. Rosendaal
2   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
3   Thrombosis and Hemostasis Research Center, Leiden University Medical Center, Leiden, The Netherlands
,
J. P. Vandenbroucke
2   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 06 November 1998

Accepted after revision 14 April 1999

Publication Date:
09 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Recently, it has been described that elevated plasma levels of factor VIII are a strong risk factor for venous thrombosis. We analysed the data of the Leiden Thrombophilia Study, a population based case-control study on the causes of venous thrombosis, to verify whether the risk due to oral contraceptive use was higher in women with higher factor VIII levels. Furthermore we investigated the joint risk of high factor VIII levels and oral contraceptive use.

We selected 155 premenopausal women with deep-vein thrombosis and 169 control subjects, aged 15-49, who were at the time of their thrombosis (or similar date in control) not pregnant, nor in the puerperium, did not have a recent miscarriage, and were not using injectable progestogens. Of the patients, 109 (70%) women had used oral contraceptives during the month preceding their deep-vein thrombosis, in contrast to 65 (38%) of the control subjects (index date), yielding an odds ratio for oral contraceptive use of 3.8 (95% CI 2.4-6.0). Of the women who suffered a deep-vein thrombosis 56 (36%) had high factor VIII levels (≥150 IU/dl) as compared with 29 (17%) of the control subjects, yielding an odds ratio for high factor VIII of 4.0 (95% CI 2.0-8.0), relative to factor VIII levels <100 IU/dl. The joint effect of oral contraceptive use and high factor VIII resulted in an odds ratio of 10.3 (95% CI 3.7-28.9), comparing women who had both with women who had neither. We conclude that there is an increase in risk due to oral contraceptive use in women with higher factor VIII levels and that both factors have additive effects.

 

  • References

  • 1 Bloemenkamp KWM, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Evidence that currently available pills are associated with cardiovascular disease: venous disease. In: Hannaford PC, Webb AMC. Evidence-guided Prescribing of the Pill. Carnforth, UK: Parthenon Publishing; 1996: 61-76.
    Search in Google Scholar
  • 2 Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453-7.
    CrossrefPubMedSearch in Google Scholar
  • 3 Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
    CrossrefPubMedSearch in Google Scholar
  • 4 O’Donnell J, Tuddenham EG, Manning R. et al. High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 1997; 77: 825-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Koster T, Rosendaal FR, Ronde H de, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-6.
    CrossrefPubMedSearch in Google Scholar
  • 6 Kamphuisen PW, Houwing-Duistermaat JJ, van Houwelingen HC, Eikenboom JC, Bertina RM, Rosendaal FR. Familial clustering of factor VIII and von Willebrand factor levels. Thromb Haemost 1998; 79: 323-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Rosendaal FR. Risk factors for venous thrombosis: prevalence, risk, and interaction. Seminars in Hematology 1997; 34: 171-87.
    PubMedSearch in Google Scholar
  • 8 Rosendaal FR. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost 1997; 78: 1-6.
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Jick H, Slone D, Westerholm B, Inman WHW, Vessey MP, Shapiro S, Lewis GP, Worcester J. Venous thromboembolic disease and ABO blood type. A cooperative study. Lancet 1969; 1: 539-42.
    PubMedSearch in Google Scholar
  • 10 Talbot S, Wakley EJ, Ryrie D, Langman MJ. ABO blood-groups and venous thromboembolic disease. Lancet 1970; 1: 1257-9.
    PubMedSearch in Google Scholar
  • 11 Bates M. Venous thromboembolic disease and ABO blood type. Lancet 1971; 1: 239.
    PubMedSearch in Google Scholar
  • 12 Talbot S, Wakley EJ, Langman MJ. A19 A29 B, and O blood-groups, Lewis blood-groups, and serum triglyceride and cholesterol concentrations in patients with venous thromboembolic disease. Lancet 1972; 1: 1152-4.
    PubMedSearch in Google Scholar
  • 13 Hill H, Loudon NB, Pitcher CS, Pocock VM. Venous thromboembolic disease and ABO blood type. Lancet 1969; I: 623.
    PubMedSearch in Google Scholar
  • 14 Mourant AE, Kopec AC, Domaniewska-Sobczak K. Blood-groups and blood-clotting. Lancet 1971; 1: 223-7.
    PubMedSearch in Google Scholar
  • 15 Westerholm B, Wiechel B, Eklund G. Oral contraceptives, venous thromboembolic disease, and ABO blood type. Lancet 1971; Sept. 18 664.
    PubMedSearch in Google Scholar
  • 16 Allan TM. ABO blood-groups and venous thromboembolism. Lancet 1971; 2: 1209-10.
    PubMedSearch in Google Scholar
  • 17 Preston AE, Barr A. Br J Haematol 1964; 10: 238.
    CrossrefPubMedSearch in Google Scholar
  • 18 Wahlberg TB, Blombäck M, Magnusson D. Influence of sex, blood group, secretor character, smoking habits, acetylsalicylic acid, oral contraceptives, fasting and general health state on blood coagulation variables in randomly selected young adults. Haemostasis 1984; 14: 312-9.
    PubMedSearch in Google Scholar
  • 19 Balleisen L, Bailey J, Epping PH, Schulte H. van de Loo Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: I. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using, and menopause. Thromb Haemost 1985; 54: 475-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Daume E. Influence of modern low-dose oral contraceptives on hemostasis. Adv Contraception 1990; 6 Suppl 51-68.
    PubMedSearch in Google Scholar
  • 21 Robinson GE. Low-dose combined oral contraceptives. British J Obstet Gynaecol 1994; 101: 1036-42.
    PubMedSearch in Google Scholar
  • 22 Fotherby K, Caldwell ADS. New progestogens in oral contraception. Contraception 1994; 49: 1-32.
    CrossrefPubMedSearch in Google Scholar
  • 23 Winkler UH. Effects on hemostatic variables of desogestrel- and gestodene-containing oral contraceptives in comparison with levonorgestrel-containing oral contraceptives; a review. Am J Obstet Gynecology 1998; 179: 551-61.
    PubMedSearch in Google Scholar
  • 24 Kluft C, Lansink M. Effect of oral contraceptives on haemostasis variables. Thromb Haemost 1997; 78: 315-26.
    Thieme ConnectPubMedSearch in Google Scholar