Contraceptive counseling for women with inherited thrombophilias
- Tanya Siddiqi, MD
Tanya Siddiqi, MD
- Assistant Professor/Staff Physician
- Department of Hematology/Hematopoietic Cell Transplantation
- City of Hope National Medical Center
- Kenneth A Bauer, MD
Kenneth A Bauer, MD
- Professor of Medicine
- Harvard Medical School
- Robert L Barbieri, MD
Robert L Barbieri, MD
- Editor-in-Chief — Obstetrics, Gynecology and Women's Health
- Section Editor — General Gynecology and Female Reproductive Endocrinology
- Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
Inherited thrombophilia is a genetic tendency to venous thrombosis (VTE), including deep vein thrombosis (DVT), pulmonary embolism, and cerebral vein thrombosis. Women with an inherited thrombophilia are at higher risk of VTE, especially during use of estrogen-progestin contraceptives and pregnancy. In making contraceptive choices, affected women need to balance the risk of VTE associated with use of various types of hormonal contraception against the risk of VTE associated with an unintended pregnancy resulting from use of less effective contraceptive methods.
This topic will discuss contraceptive counseling for women with an inherited thrombophilia. Other issues related to inherited thrombophilias are reviewed in detail separately:
- 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.
- Bergendal A, Persson I, Odeberg J, et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014; 124:600.
- Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report (MMWR). U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. Adapted from the World Health Organization Medical Eligibility Criteria for Contraceptive Use, 4th edition. Early release - May 28, 2010. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr59e0528a1.htm (Accessed on May 28, 2010).
- Heinemann LA, Dinger JC. Range of published estimates of venous thromboembolism incidence in young women. Contraception 2007; 75:328.
- Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009; 339:b2890.
- 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.
- 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.
- Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med 2001; 344:1527.
- 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.
- 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.
- 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.
- 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.
- Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2015; 350:h2135.
- 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.
- Bitzer J, Amy JJ, Beerthuizen R, et al. Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism. J Fam Plann Reprod Health Care 2013; 39:156.
- Konkle BA. Counseling of women with thrombophilia. Thromb Res 2005; 115 Suppl 1:44.
- 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.
- 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.
- 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.
- 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.
- Creinin MD, Lisman R, Strickler RC. Screening for factor V Leiden mutation before prescribing combination oral contraceptives. Fertil Steril 1999; 72:646.
- 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.
- 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.
- Wu O, Greer IA. Is screening for thrombophilia cost-effective? Curr Opin Hematol 2007; 14:500.
- Middeldorp S. Thrombosis in women: what are the knowledge gaps in 2013? J Thromb Haemost 2013; 11 Suppl 1:180.
- Vandenbroucke JP, van der Meer FJ, Helmerhorst FM, Rosendaal FR. Factor V Leiden: should we screen oral contraceptive users and pregnant women? BMJ 1996; 313:1127.
- Dalen JE. Should patients with venous thromboembolism be screened for thrombophilia? Am J Med 2008; 121:458.
- GENERAL PRINCIPLES
- NONHORMONAL METHODS
- PROGESTIN-ONLY METHODS
- ESTROGEN-PROGESTIN METHODS
- Risk of venous thrombosis
- Indications for screening for inherited thrombophilias
- Individualized risk-based counseling
- - Personal history of venous thrombosis
- - Familial, but no personal, history of VTE
- - No personal or family history of VTE, but positive testing for inherited thrombophilia
- - Choice of estrogen-progestin oral contraceptive
- SUMMARY AND RECOMMENDATIONS
- Screening for inherited thrombophilia
- Contraception recommendations