What is the risk of low molecular weight heparin (LMWH) or unfractionated heparin (UFH) to the fetus in a pregnant woman with pulmonary embolism (PE)?

Risk of Heparin to a Fetus in Maternal Pulmonary Embolism

Low molecular weight heparin (LMWH) and unfractionated heparin (UFH) do not cross the placenta and are safe for the fetus when used to treat pulmonary embolism (PE) in pregnant women. 1

Safety Profile of Heparin in Pregnancy

• Both LMWH and UFH are considered safe during pregnancy as they do not cross the placenta, preventing fetal exposure and potential teratogenic effects 1
• LMWH is recommended over UFH for the prevention and treatment of venous thromboembolism (VTE) in pregnant women (Grade 1B recommendation) 1
• The FDA label for heparin confirms that in published reports, heparin exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes in humans 2

Comparative Safety of LMWH vs UFH

LMWH offers several advantages over UFH:

• Lower risk of heparin-induced thrombocytopenia (HIT) 1
• Reduced risk of osteoporosis with long-term use 1, 3
• Extended use of UFH during pregnancy has been associated with a 2.2% risk of osteoporotic fracture 1
• No monitoring required for LMWH, making it more convenient for pregnant patients 4

Fetal Outcomes with Heparin Therapy

• In a systematic review of pregnant women without comorbid conditions treated with LMWH, only 3.1% experienced adverse fetal outcomes, which is comparable to the normal population 3
• A descriptive evaluation of UFH use during pregnancy showed fetal demise in 7.8% of pregnancies, though none occurred in pregnancies treated for acute VTE 5
• Animal studies showed no evidence of teratogenic effects with heparin, though early embryo-fetal death was observed at doses approximately 10 times the maximum recommended human dose 2

Contraindications and Alternatives

• Vitamin K antagonists (e.g., warfarin) are contraindicated during pregnancy, especially in the first trimester and late pregnancy, as they cross the placenta and can cause fetal complications including teratogenicity, pregnancy loss, and fetal bleeding 1, 4
• Oral direct thrombin inhibitors (e.g., dabigatran) and factor Xa inhibitors (e.g., rivaroxaban, apixaban) should be avoided during pregnancy (Grade 1C recommendation) 1
• Fondaparinux and parenteral direct thrombin inhibitors should be limited to pregnant women with severe allergic reactions to heparin who cannot receive danaparoid 1

Special Considerations

• In pregnant women with significant renal dysfunction (glomerular filtration rate <30 mL/min), UFH with activated partial thromboplastin time monitoring is preferred over LMWH 1
• For women with mechanical heart valves requiring anticoagulation during pregnancy, management is more complex and controversial, as warfarin appears safer for the mother but heparin is associated with less fetal morbidity 4
• Preservative-free heparin sodium injection is recommended when heparin therapy is needed during pregnancy to avoid potential adverse effects from preservatives like benzyl alcohol 2

Duration of Treatment

• For pregnant women with acute VTE, anticoagulant therapy should be continued for at least 6 weeks postpartum (for a minimum total duration of 3 months) 1
• Treatment can be safely continued during breastfeeding, as both LMWH and UFH are recommended for lactating women who wish to breastfeed 1