Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:

Subscribers log in here

Contraception for women with inherited thrombophilias


Inherited thrombophilia is a genetic tendency to venous thromboembolism (VTE), including deep vein thrombosis (DVT), pulmonary embolism, and cerebral vein thrombosis. Women with inherited thrombophilias are at higher risk of VTE, especially in settings such as during use of estrogen-progestin contraceptives or pregnancy (the risk of VTE is much higher in pregnancy/postpartum than with use of an estrogen-progestin contraceptive [1]). In making contraceptive choices, women need to balance the risk of VTE associated with use of effective contraception against the risk of VTE associated with an unintended pregnancy resulting from use of less effective contraceptive methods.


Factor V Leiden (FVL) is the most common hereditary risk factor for VTE. In unselected Caucasian patients with an initial symptomatic episode of DVT, 12 to 20 percent will be heterozygous for the FVL mutation compared with approximately 6 percent of asymptomatic controls [2]. The prevalence of FVL heterozygosity in Caucasian American women is about 4.85 percent and is less frequent in Hispanic Americans (2.21 percent), Native Americans (1.25 percent), African Americans (1.23 percent), and Asian Americans (0.45 percent) [3].

The prothrombin gene mutation (G20210A) is the second most common genetic risk factor for VTE: G20210A heterozygosity is identified in 6 percent of patients with VTE compared with 2 percent of asymptomatic controls; deficiencies in protein S, protein C, and antithrombin account for most of the remaining cases [2,4].

Inherited thrombophilia is discussed in detail separately:


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Aug 2014. | This topic last updated: Apr 1, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
  1. van Vlijmen EF, Veeger NJ, Middeldorp S, et al. Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception. Blood 2011; 118:2055.
  2. Bauer KA. The thrombophilias: well-defined risk factors with uncertain therapeutic implications. Ann Intern Med 2001; 135:367.
  3. Ridker PM, Miletich JP, Hennekens CH, Buring JE. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA 1997; 277:1305.
  4. Mohllajee AP, Curtis KM, Martins SL, Peterson HB. Does use of hormonal contraceptives among women with thrombogenic mutations increase their risk of venous thromboembolism? A systematic review. Contraception 2006; 73:166.
  5. Domagala TB, Adamek L, Nizankowska E, et al. Mutations C677T and A1298C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease. Blood Coagul Fibrinolysis 2002; 13:423.
  6. McColl MD, Ellison J, Reid F, et al. Prothrombin 20210 G-->A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy. BJOG 2000; 107:565.
  7. Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Contraception 1998; 57:315.
  8. Vasilakis C, Jick H, del Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet 1999; 354:1610.
  9. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009; 339:b2890.
  10. van Hylckama Vlieg A, Helmerhorst FM, Rosendaal FR. The risk of deep venous thrombosis associated with injectable depot-medroxyprogesterone acetate contraceptives or a levonorgestrel intrauterine device. Arterioscler Thromb Vasc Biol 2010; 30:2297.
  11. Mantha S, Karp R, Raghavan V, et al. Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis. BMJ 2012; 345:e4944.
  12. Dugdale M, Masi AT. Hormonal contraception and thromboembolic disease: effects of the oral contraceptives on hemostatic mechanisms. A review of the literature. J Chronic Dis 1971; 23:775.
  13. Vandenbroucke JP, Koster T, Briët E, et al. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344:1453.
  14. Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med 2001; 344:1527.
  15. Jick H, Jick SS, Gurewich V, et al. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346:1589.
  16. Cosmi B, Legnani C, Bernardi F, et al. Role of family history in identifying women with thrombophilia and higher risk of venous thromboembolism during oral contraception. Arch Intern Med 2003; 163:1105.
  17. Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med 2004; 164:1965.
  18. van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009; 339:b2921.
  19. Spitzer WO, Lewis MA, Heinemann LA, et al. Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women. BMJ 1996; 312:83.
  20. Konkle BA. Counseling of women with thrombophilia. Thromb Res 2005; 115 Suppl 1:44.
  21. van Vlijmen EF, Brouwer JL, Veeger NJ, et al. Oral contraceptives and the absolute risk of venous thromboembolism in women with single or multiple thrombophilic defects: results from a retrospective family cohort study. Arch Intern Med 2007; 167:282.
  22. Heinemann LA, Dinger JC. Range of published estimates of venous thromboembolism incidence in young women. Contraception 2007; 75:328.
  23. Creinin MD, Lisman R, Strickler RC. Screening for factor V Leiden mutation before prescribing combination oral contraceptives. Fertil Steril 1999; 72:646.
  24. Wu O, Robertson L, Langhorne P, et al. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost 2005; 94:17.
  25. Wu O, Robertson L, Twaddle S, et al. Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis. Br J Haematol 2005; 131:80.
  26. Wu O, Greer IA. Is screening for thrombophilia cost-effective? Curr Opin Hematol 2007; 14:500.
  27. Grimes DA, Stuart GS, Levi EE. Screening women for oral contraception: can family history identify inherited thrombophilias? Obstet Gynecol 2012; 120:889.