What is the recommended anticoagulation therapy for pregnant women at high risk of thromboembolic events?

From the Guidelines

Low molecular weight heparin (LMWH) is the recommended anticoagulation therapy for pregnant women at high risk of thromboembolic events. According to the most recent and highest quality study 1, LMWH is preferred over unfractionated heparin or warfarin due to its safety profile and effectiveness. The study suggests that LMWH does not cross the placenta, has a more predictable dose response, requires less monitoring, and carries a lower risk of heparin-induced thrombocytopenia and osteoporosis.

Some key points to consider when using LMWH in pregnant women include:

• Enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily) or dalteparin (100 IU/kg twice daily or 200 IU/kg once daily) are the preferred options, with dosing based on pre-pregnancy or early pregnancy weight 1.
• Treatment should begin as soon as pregnancy is confirmed and continue throughout pregnancy and for at least 6 weeks postpartum, with the total duration of therapy being at least 3 months 1.
• Regular monitoring of anti-Factor Xa levels is recommended, aiming for peak levels of 0.6-1.0 IU/mL for twice-daily dosing or 1.0-2.0 IU/mL for once-daily dosing 1.
• Warfarin is contraindicated during pregnancy, especially in the first trimester, due to its teratogenic effects 1.
• Direct oral anticoagulants (DOACs) are also not recommended during pregnancy due to limited safety data and evidence of placental transfer 1.

It's worth noting that the choice of anticoagulation strategy may vary depending on individual patient factors, such as the presence of mechanical heart valves or a history of thromboembolic events 1. However, overall, LMWH remains the preferred option for anticoagulation therapy in pregnant women at high risk of thromboembolic events.

From the FDA Drug Label

Available data from published literature and postmarketing reports have not reported a clear association with fondaparinux sodium and adverse developmental outcomes Fondaparinux sodium plasma concentrations obtained from four women treated with fondaparinux sodium during pregnancy and their newborn infants demonstrated low placental transfer of fondaparinux sodium In animal reproduction studies, there was no evidence of adverse developmental outcomes when fondaparinux sodium was administered to pregnant rats and rabbits during organogenesis at doses 32 and 65 times, respectively, the recommended human dose based on body surface area. Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. Use of anticoagulants, including fondaparinux sodium, may increase the risk of bleeding in the fetus and neonate.

The recommended anticoagulation therapy for pregnant women at high risk of thromboembolic events is not explicitly stated in the provided drug label. However, fondaparinux sodium may be considered as an option, given its low placental transfer and lack of reported adverse developmental outcomes.

• Key considerations for using fondaparinux sodium in pregnant women include:
  • Monitoring for bleeding or unexpected changes in coagulation parameters
  • Careful consideration of the risk of bleeding in the fetus and neonate
  • Potential use of a shorter-acting anticoagulant as delivery approaches 2

From the Research

Anticoagulation Therapy in Pregnancy

The use of anticoagulants in pregnancy is crucial for preventing thromboembolic events, which are a leading cause of maternal mortality in the developed world 3.

Recommended Anticoagulation Therapy

For pregnant women at high risk of thromboembolic events, the recommended anticoagulation therapy centers on the use of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) 3. LMWHs, such as enoxaparin and dalteparin, have clinical and practical advantages compared with UFH, including improved safety and patient convenience with once daily dosing for the majority of women 3.

Key Considerations

When considering anticoagulation therapy in pregnancy, the following key points should be taken into account:

• The hypercoagulable state of pregnancy increases the risk of thromboembolic events 4, 5
• The choice of anticoagulant requires consideration of maternal risks, potential for teratogenicity, the underlying condition necessitating the treatment, and cost 5
• Current guidelines support the selective use of aspirin, heparin, and warfarin in pregnant women 4
• The decision to treat with antiplatelets and anticoagulants during pregnancy can be challenging and requires thoughtful discussion between patient and provider 4

Management and Prevention of Thromboembolism

The management and prevention of thromboembolism in pregnancy include:

• Treatment of acute thrombotic events
• Prophylaxis for those at increased risk of thrombotic events 6
• Screening for thromboembolism risk and management of anticoagulation around the time of delivery 6