Bayer Pharma AG

Essence of this Article

The American College of Chest Physicians (ACCP) guidelines recommend thromboprophylaxis with low molecular weight heparin (LMWH) for the prevention of venous thromboembolism (VTE) in pregnant women with a history of VTE and a moderate-to-high risk of recurrence. Thromboprophylaxis is not recommended in certain cases. Vitamin K antagonist (VKA) use is not recommended during pregnancy, but the use of warfarin and acenocoumarol are options after childbirth. The use of fondaparinux and parenteral direct thrombin inhibitors should be limited to women with severe allergic reactions to heparin. Novel oral agents, such as dabigatran, rivaroxaban, apixaban and edoxaban, are not recommended in current guidelines owing to lack of clinical data in pregnant women.

Guideline Recommendations

For the prevention of VTE in pregnant women with a history of VTE and a moderate-to-high risk of recurrence, the ACCP guidelines recommend thromboprophylaxis with LMWH during the first, second and third trimesters, and during late pregnancy.267 European Society of Cardiology (ESC) guidelines for the management of PE in pregnancy, issued in 2014, broadly concur with the ACCP recommendations.533

Thromboprophylaxis is not recommended in women:

  • With inherited thrombophilia and a history of pregnancy complications
  • Who have had ≥2 miscarriages (but without antiphospholipid antibody syndrome or thrombophilia)267

For the treatment of VTE in pregnant women, LMWH continued for ≥6 weeks postpartum is recommended.

For prophylaxis or treatment:

  • VKA use is not recommended during pregnancy, but the use of warfarin and acenocoumarol are options after childbirth.267 For women who are attempting to conceive and who are receiving long-term VKA therapy, switching from VKAs to LMWH is suggested only once pregnancy is achieved267
  • The use of fondaparinux and parenteral direct thrombin inhibitors should be limited to women with severe allergic reactions to heparin (including heparin-induced thrombocytopenia [HIT]) who cannot receive danaparoid, which is effective in pregnant women with HIT, and does not cross the placenta267
  • Newer oral agents, such as the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors rivaroxaban, apixaban and edoxaban, are not recommended in current guidelines owing to lack of clinical data in pregnant women267
    • These agents are all contraindicated during pregnancy and in lactating women274-276
    • Preclinical studies have shown that rivaroxaban can pass through the placenta and can be secreted into breast milk,274 and this may also be expected for other small molecule substances

Click here for a summary of the ACCP guideline recommendations for the prevention and treatment of VTE in pregnant women.

ACCP guideline recommendations for prevention and treatment of VTE in pregnancy267

IndicationTherapy as recommended by the ACCP
Prevention of VTE:
in pregnant women with a history of VTE
  • Prophylactic- or intermediate-dose LMWH or VKA (INR 2.0–3.0) postpartum for 6 weeks is suggested
  • Low risk of recurrent VTE (single episode of VTE associated with a transient risk factor not related to pregnancy or use of oestrogen): clinical vigilance antepartum is suggested
  • Moderate to high risk of recurrent VTE (single unprovoked VTE, pregnancy- or oestrogen-related VTE, or multiple prior unprovoked VTE not receiving long-term anticoagulation): prophylactic- or intermediate-dose LMWH antepartum is suggested
  • In women receiving long-term VKA therapy: adjusted-dose LMWH or 75% of a therapeutic dose of LMWH throughout pregnancy followed by resumption of long-term anticoagulant postpartum is suggested
Prevention of VTE:
in pregnant women with thrombophilia and no prior VTE
  • Homozygous for Factor V Leiden or G20210A mutation and family history of VTE: antepartum prophylaxis with prophylactic- or intermediate-dose LMWH and postpartum prophylaxis for 6 weeks with prophylactic- or intermediate-dose LMWH or VKA (INR 2.0–3.0) is suggested
  • All other thrombophilias and no prior VTE with family history of VTE: antepartum clinical vigilance and prophylactic- or intermediate dose LMWH postpartum or VKAs (INR 2.0–3.0) in women who are not protein C or S deficient is suggested
  • No prior history of VTE, homozygous for Factor V Leiden or the prothrombin G20210A mutation and family history of VTE: antepartum clinical vigilance and prophylactic- or intermediate dose LMWH or VKAs (INR 2.0–3.0) postpartum for 6 weeks is suggested
  • All other thrombophilias but no prior VTE or family history of VTE: clinical vigilance antepartum and postpartum is suggested
Treatment of acute VTE
  • LMWH recommended over UFH and VKAs
  • Continued treatment for ≥6 weeks postpartum is suggested (minimum total duration of 3 months)
  • Discontinuation of LMWH or UFH ≥24 hours prior to induction of labour or caesarean section
Source: Bates SM et al. (2012).267
ACCP, American College of Chest Physicians; INR, international normalized ratio; LMWH, low molecular weight heparin; UFH, unfractionated heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism.

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