What is the use of Direct Oral Anticoagulants (DOACs) in pregnancy?

From the Guidelines

Direct oral anticoagulants (DOACs) are not recommended during pregnancy due to concerns about safety and potential fetal harm. The most recent guidelines from the European Heart Journal 1 emphasize that pregnancy is associated with a hypercoagulable state and increased risk of thromboembolism, and the preferred agents for anticoagulation of atrial fibrillation during pregnancy are unfractionated or low molecular weight heparins (LMWHs), which do not cross the placenta.

The use of DOACs in pregnancy is limited by the lack of safety data and concerns about embryo-fetal toxicity based on animal studies. According to the 2024 ESC guidelines 1, vitamin K antagonists should be avoided in the first trimester and from week 36 onwards, and DOACs are not recommended during pregnancy.

In cases where a woman becomes pregnant while on a DOAC, immediate transition to LMWH is recommended. The dosing of LMWH depends on the indication and patient characteristics, with therapeutic dosing (e.g., enoxaparin 1 mg/kg twice daily) for conditions like venous thromboembolism. LMWH should be continued throughout pregnancy and for at least 6 weeks postpartum, with potential transition to warfarin after delivery if long-term anticoagulation is needed.

Key considerations for the management of DOACs in women of childbearing potential include:

• Documented counseling prior to commencement of DOACs, with emphasis on avoidance of pregnancy while on a DOAC by use of adequate and appropriate contraception 1
• Switching to an alternative anticoagulant pre-conceptually, with the main alternative anticoagulant options being VKAs or LMWH 1
• Discontinuing DOACs immediately and commencing LMWH in women who unintentionally become pregnant while on a DOAC 1
• Early obstetric review and fetal monitoring in women who become pregnant while on a DOAC and who decide to continue with pregnancy 1

Overall, the management of DOACs in pregnancy requires a careful and individualized approach, with consideration of the potential risks and benefits of anticoagulation therapy. The priority should always be to protect the developing fetus from potential teratogenic effects while maintaining effective maternal anticoagulation.

From the FDA Drug Label

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnancy confers an increased risk of thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. Use of anticoagulants, including apixaban, may increase the risk of bleeding in the fetus and neonate. Labor or delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. Apixaban tablets use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas Consider use of a shorter acting anticoagulant as delivery approaches

The use of Direct Oral Anticoagulants (DOACs), such as apixaban, in pregnancy is associated with an increased risk of bleeding in the fetus and neonate. Pregnant women with underlying thromboembolic disease are at higher risk for thromboembolism.

• Key considerations for the use of apixaban in pregnancy include:
  • Increased risk of bleeding in the fetus and neonate
  • Risk of epidural or spinal hematomas during labor or delivery, especially with neuraxial anesthesia
  • Recommendation to consider a shorter acting anticoagulant as delivery approaches 2

From the Research

Use of Direct Oral Anticoagulants (DOACs) in Pregnancy

• The use of DOACs in pregnancy is a topic of interest due to their increasing popularity as anticoagulants 3.
• A retrospective cohort study found that DOAC exposure in pregnancy does not suggest a high risk of embryopathy, with 21 out of 336 pregnancies showing fetal abnormalities, and 12 of these being adjudicated as major birth defects potentially related to DOAC exposure 3.
• The study also highlighted the need for a more robust system of reporting pregnancy outcomes after DOAC exposure, as data are often missing important details 3.

Bleeding Risks Associated with DOACs

• DOACs have been associated with bleeding risks, and patients often stop taking them due to nonmajor bleeding, which may lead to venous thromboembolism (VTE) recurrence 4.
• A network meta-analysis found that apixaban had the lowest risk of nonmajor bleeding among DOACs, regardless of whether it was used for preventing or treating VTE 4.
• Another study discussed the interferences of anticoagulants, including DOACs, on lupus anticoagulant testing, and strategies to mitigate these interferences, such as avoiding testing while patients are on anticoagulants or using anticoagulant neutralizers 5.

Measurement of DOACs

• A study evaluated the use of heparin-calibrated anti-factor Xa assay for measuring the level of DOACs, such as apixaban, rivaroxaban, and edoxaban 6.
• The study found that unfractionated heparin (UHF)/low molecular weight heparin (LMWH)-calibrated AXA may be useful in determining the presence of DOACs at the cutoff level for antidote treatment in rivaroxaban and apixaban, but not in edoxaban 6.

Clinical Implications

• The bleeding risks associated with DOACs are a concern, and an update on these risks highlighted the need for optimal laboratory monitoring of anticoagulation, perioperative management, and treatment of bleeding 7.
• The use of DOACs in pregnancy requires careful consideration, and healthcare providers should be aware of the potential risks and benefits of these medications in this population 3.