Which Thrombophilias in Pregnancy Warrant Thromboprophylaxis? 

BACKGROUND AND PURPOSE:

  • Thrombophilias are a known risk factor for venous thromboembolism (VTE) in pregnancy
  • Pregnancy increases the risk of VTE in pregnancy approximately five to sixfold
  • Data is limited on absolute risk of pregnancy-associated VTE in women with thrombophilias and there are no meta-analyses
  • Croles et al. (BMJ, 2017) sought to establish evidence that could be used to update guidelines for prevention of VTEs in pregnant women with heritable thrombophilias

METHODS:

  • Systematic Review and meta-analysis
  • Included studies with information on specific inherited thrombophilias
    • Antithrombin deficiency
    • Protein C deficiency
    • Protein S deficiency
    • Factor V Leiden mutation (heterozygous or homozygous)
    • Prothrombin G20210A mutation (heterozygous or homozygous)
    • Compound heterozygous factor V Leiden and prothrombin G20210A mutation
  • VTE was considered established if it was confirmed by objective means, or when the patient had received a full course of a full dose anticoagulant treatment without objective testing
  • Studies were classified as family and non-family studies due to increased risk based on family history
    • Non-family cohort studies rarely included data on women with high risk thrombophilias

RESULTS:

  • 36 studies were included in the systematic review (12 case-control; 24 cohort studies)
    • 41,297 pregnancies included
  • All thrombophilias increased the risk for pregnancy-associated VTE (probabilities ≥91%)
  • Thrombophilias with high absolute risks included the following (absolute risk, using 95% credible interval range)
    • Antithrombin deficiency
      • Antepartum: 7.3% (1.8% to 15.6%)
      • Postpartum: 11.1 (3.7% to 21.0%)
    • Protein C deficiency
      • Antepartum: 3.2% (0.6% to 8.2%)
      • Postpartum: 5.4% (0.9% to 13.8%)
    • Protein S deficiency
      • Antepartum: 0.9% (0.0% to 3.7%)
      • Postpartum: 4.2% (0.7% to 9.4%)
    • Homozygous factor V Leiden
      • Antepartum: 2.8% (0.0% to 8.6%)
      • Post partum: 2.8% (0.0% to 8.8%)
    • Absolute combined antepartum and postpartum risks for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, or compound heterozygous factor V Leiden and prothrombin G20210A mutations were all below 3% (cut-off for thromboprophylaxis used in some guidelines)

CONCLUSION:

  • Based on 3% risk cut-offs, authors draw the following conclusions for antepartum prophylaxis and prophylaxis up to six weeks postpartum for women with no previous VTE
    • Suggest prophylaxis for women with antithrombin and protein C deficiency if they have a positive family history.
    • Consider prophylaxis for women with homozygous factor V Leiden mutations for women with a family history and additional risk factors for VTE
    • Suggest prophylaxis for women with protein S deficiency and a positive family only in postpartum
    • Cannot give recommendations for homozygous prothrombin G20210A mutation due to lack of cohort data
  • In contrast, women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutation, or compound heterozygous factor V Leiden and prothrombin G20210A mutation should generally not receive thrombosis prophylaxis on the basis of thrombophilia and family history alone

Learn More – Primary Sources:

Pregnancy, thrombophilia, and the risk of a first venous thrombosis: systematic review and bayesian meta-analysis