What is the safety of Enoxaparin (low molecular weight heparin) during pregnancy?

From the Guidelines

Enoxaparin is considered safe during pregnancy, with a preferred thromboprophylactic dose of 40 mg subcutaneously once a day, and is often the preferred anticoagulant for pregnant women who require blood thinning therapy. The safety of enoxaparin during pregnancy is supported by its advantages, including better bioavailability, longer half-life, more predictable anticoagulation effect, less bleeding risks, and less risk of heparin-induced thrombocytopenia and osteopenia 1.

Key Considerations

• Enoxaparin does not cross the placenta, which means it doesn't directly affect the developing fetus.
• Typical prophylactic dosing ranges from 40mg once daily, with obese women potentially requiring higher doses, such as 40 mg subcutaneously every 12 hours or a weight-based prophylactic dose of 0.5 mg/kg subcutaneously every 12 hours 1.
• Regular monitoring of anti-Factor Xa levels is recommended, especially for therapeutic dosing.
• Common side effects include injection site bruising and, rarely, bleeding complications.
• Patients should be taught proper injection technique for self-administration in the abdominal area.

Administration and Monitoring

• Enoxaparin should be discontinued 24 hours before planned delivery or cesarean section to reduce bleeding risk.
• After delivery, enoxaparin can be resumed 6-12 hours after vaginal delivery or 12-24 hours after cesarean section if there are no bleeding concerns.
• Unlike warfarin, enoxaparin is also safe during breastfeeding as it does not pass significantly into breast milk.
• The American Society of Hematology 2018 guidelines for management of venous thromboembolism also support the use of low molecular weight heparin, such as enoxaparin, for thromboprophylaxis in pregnant women 1.

Special Considerations

• Pregnant women may require dose adjustments as pregnancy progresses due to physiological changes affecting drug metabolism.
• The optimal dose for obese women is unknown, but some evidence supports the use of intermediate doses of enoxaparin or a weight-based prophylactic dose 1.

From the Research

Safety of Enoxaparin During Pregnancy

The safety of enoxaparin, a low molecular weight heparin, during pregnancy has been evaluated in several studies.

• Enoxaparin does not cross the placenta and is safe for the fetus 2.
• Maternal side effects are uncommon and include mild localized allergic reactions in 2% and increased bleeding in 2%, which is dose dependent 2.
• Heparin-induced thrombocytopenia is very rare and bone resorption is not clinically relevant 2.

Efficacy of Enoxaparin in Preventing Thromboembolism

Enoxaparin has been shown to be effective in preventing thromboembolism during pregnancy.

• A study of 57 pregnancies in 50 women found that there were no thromboembolic events in the thromboprophylaxis group 3.
• Another study of 35 pregnant patients with deep vein thrombosis found that enoxaparin therapy was effective in preventing further thromboembolic events 4.
• A study of 52 women who received subcutaneous enoxaparin found that therapeutic enoxaparin prevented further thromboembolism without complications 5.

Pharmacokinetics of Enoxaparin During Pregnancy

The pharmacokinetics of enoxaparin during pregnancy have been evaluated in several studies.

• A population pharmacokinetics study found that clearance of enoxaparin was higher in pregnant women throughout pregnancy compared to nonpregnant women 6.
• The volume of distribution was influenced by stage of pregnancy, with an initial rise paralleling the woman's increase in body weight during the first two trimesters, followed by an additional increase during the last 2 months of pregnancy 6.
• The study recommended the administration of doses normalized for body weight changes to counteract enoxaparin pharmacokinetic changes that accompany various stages of pregnancy 6.

Monitoring and Dosing of Enoxaparin

The monitoring and dosing of enoxaparin during pregnancy have been evaluated in several studies.

• A study found that the enoxaparin dose/kg correlated poorly with anti-Xa levels, and dose adjustments were made 5.
• Another study found that a dose of 40 mg once daily throughout pregnancy provided satisfactory anti-factor Xa levels and appeared effective in preventing venous thromboembolism 3.
• The use of anti-Xa monitoring to guide enoxaparin dosing during pregnancy has been recommended 5, 6.