What are the effects and bleeding outcomes of Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA), and Direct Oral Anticoagulants (DOACs) in pregnancy?

From the Guidelines

Low molecular weight heparins (LMWHs) are the preferred anticoagulants during pregnancy due to their safety profile, as they do not cross the placenta and have minimal bleeding risks. The most recent and highest quality study, published in 2024 1, supports the use of LMWHs as the preferred anticoagulants during pregnancy. LMWHs, such as enoxaparin (1mg/kg twice daily or 1.5mg/kg once daily), require monitoring only in specific cases like renal impairment or extreme weights.

Key Considerations for Anticoagulation in Pregnancy

• Vitamin K antagonists (VKAs) like warfarin should be avoided during pregnancy, especially in the first trimester (risk of embryopathy) and near delivery (fetal bleeding risk) 1.
• If absolutely necessary, warfarin can be used during the second trimester with close monitoring (target INR 2-3), but must be switched to LMWH before delivery.
• Direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, dabigatran, and edoxaban are contraindicated throughout pregnancy as they cross the placenta and have been associated with embryopathy and fetal bleeding 1.

Management of Anticoagulation in Pregnancy

• For pregnant women requiring anticoagulation, LMWH should be initiated early and continued throughout pregnancy, with consideration for switching to unfractionated heparin at 36 weeks to allow for neuraxial anesthesia during delivery.
• Postpartum, women can transition to warfarin or DOACs if not breastfeeding, while LMWH remains safe during lactation.
• The physiological hypercoagulable state of pregnancy increases thrombotic risk, making appropriate anticoagulation crucial, but this must be balanced against bleeding risks, particularly during delivery 1.

Bleeding Outcomes and Risks

• The risk of bleeding complications with LMWHs is low, but monitoring of plasma anti-Xa levels is necessary to adjust the dose and minimize the risk of bleeding 1.
• The use of VKAs and DOACs during pregnancy is associated with a higher risk of bleeding complications, and their use should be avoided whenever possible 1.

From the FDA Drug Label

The limited available data on apixaban tablets use in pregnant women are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse developmental outcomes. Treatment may increase the risk of bleeding during pregnancy and delivery The limited available data on dabigatran etexilate capsules use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes There are risks to the mother associated with untreated venous thromboembolism in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulants Use of anticoagulants, including apixaban, may increase the risk of bleeding in the fetus and neonate. Use of anticoagulants, including dabigatran etexilate capsules, may increase the risk of bleeding in the fetus and neonate.

The effects and bleeding outcomes of Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA), and Direct Oral Anticoagulants (DOACs) in pregnancy are not directly addressed in the provided drug labels.

• Bleeding risks are associated with the use of anticoagulants, including apixaban and dabigatran, in pregnant women.
• The limited available data on apixaban and dabigatran use in pregnant women are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse developmental outcomes.
• Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions.
• Anticoagulant use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas 2 3.

From the Research

Effects and Bleeding Outcomes of Anticoagulants in Pregnancy

The effects and bleeding outcomes of Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA), and Direct Oral Anticoagulants (DOACs) in pregnancy are as follows:

• LMWH: Studies have shown that LMWH is safe and effective in preventing major thromboembolic complications during pregnancy 4, 5, 6. The risk of maternal bleeding is not increased with LMWH use 5, and it does not cross the placenta, making it a safe option for fetal health 5.
• VKA: VKA regimens have been shown to be effective in preventing thromboembolic events, but may be associated with a higher risk of fetal wastage, particularly with high warfarin doses 7. The use of VKA during pregnancy requires careful management and monitoring.
• DOACs: There is limited evidence on the use of DOACs during pregnancy, and they are not currently recommended for use in pregnant women due to limited data on their safety and efficacy 8.

Bleeding Outcomes

Bleeding outcomes for anticoagulants in pregnancy include:

• LMWH: Low risk of maternal bleeding, with no excessive intrapartum bleeding reported in studies 4, 6.
• VKA: Higher risk of fetal wastage and potential for maternal bleeding complications, particularly with high warfarin doses 7.
• UFH: Higher risk of maternal and fetal complications, including bleeding and thromboembolic events 7, 8.

Management Recommendations

Management recommendations for anticoagulants in pregnancy include:

• LMWH: Adjusted-dose LMWH throughout pregnancy, with monitoring of anti-Xa levels 4, 8.
• VKA: Low-dose warfarin regimen, with careful monitoring of international normalized ratio (INR) levels 7, 8.
• UFH: Adjusted-dose UFH, with monitoring of activated partial thromboplastin time (aPTT) levels 8.