Grand Rounds

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

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

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)

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

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