The impact of a male or female thrombotic family history on contraceptive counseling: a cohort study

J Thromb Haemost. 2016 Sep;14(9):1741-8. doi: 10.1111/jth.13393. Epub 2016 Aug 11.


Essentials It is unknown if a male or female thrombotic family history influences risk in female relatives. We assessed thrombotic risk in female relatives of male and female patients with thrombosis. A hormonally related female thrombotic family history further increases risk in female relatives. This information could be important in counseling women on contraceptive options. Click to hear Prof. Rosendaal's perspective on venous thrombosis: etiology, pathogenesis, and prognosis

Summary: Background Women from thrombophilic families have increased risk of venous thromboembolism (VTE), which increases further during oral contraceptive (COC) use and pregnancy-postpartum. Whether this additional risk differs between relatives of male and female patients, or is different when that female patient had a hormonally related VTE (during COC use/pregnancy), is unknown. Methods One thousand five female relatives of consecutive patients with VTE from a family-based cohort were retrospectively followed for incident VTE from ages 15 to 50, first VTE, or study inclusion. Absolute and relative VTE risks adjusted for factors of patients (sex, age) and relatives (thrombophilia, COC use, pregnancy) were estimated in relatives of female and male patients and in relatives of female patients with and without hormonally related VTE. Results Absolute risk in relatives of female (0.32 [95% confidence interval [CI] 0.23-0.43]) vs. male patients (0.39 [95% CI 0.28-0.53]) was comparable. However, the heterogeneity analysis of risk estimates suggested that in relatives of female vs. male patients, the contribution of pregnancy-postpartum (hazard ratio [HR] 11.6 [95% CI 6.3-21.3] vs. HR6.6 [95% CI 2.8-15.2]) and, to a lesser extent, COC use (HR3.6 [95% CI 1.8-7.1] vs. HR2.7 [95% CI 1.5-5.0]) to the VTE risk differs. Absolute risk was significantly higher in relatives of female patients with hormonally related VTE (0.43 [95% CI 0.3-0.6]) vs. relatives of female patients without hormonally related VTE (0.13 [95% CI 0.05-0.27]), HR3.28 [95% CI 1.5-7.9]). The higher contribution of pregnancy-postpartum and COC use to the VTE risk was mainly observed in relatives of patients with hormonally related VTE. Conclusions These findings suggest that a family history from a female patient, especially when VTE was hormonally related, may further increase VTE risk in her female relatives. This information could be important in counseling women on contraceptive options.

Keywords: combined oral contraceptives; hereditary thrombophilia; venous thromboembolism.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Contraception / methods*
  • Contraceptive Agents / therapeutic use*
  • Contraceptives, Oral, Combined / adverse effects*
  • Factor V / genetics
  • Family Health
  • Female
  • Humans
  • Male
  • Mutation
  • Netherlands
  • Postpartum Period
  • Pregnancy
  • Proportional Hazards Models
  • Risk Assessment
  • Thrombophilia / genetics
  • Thrombosis / genetics*
  • Venous Thromboembolism / genetics
  • Venous Thrombosis / genetics


  • Contraceptive Agents
  • Contraceptives, Oral, Combined
  • factor V Leiden
  • Factor V