Which anticoagulants are contraindicated during pregnancy?

Anticoagulants Contraindicated in Pregnancy

Warfarin (vitamin K antagonists) is strictly contraindicated during pregnancy, especially in the first trimester and near delivery, due to its ability to cross the placenta causing embryopathy and fetal hemorrhage. 1 Direct oral anticoagulants (DOACs) are also not recommended during pregnancy due to safety concerns. 2

Warfarin Contraindication Details

• Warfarin crosses the placenta and is associated with increased risk of spontaneous abortion, prematurity, and stillbirth 2
• The FDA label explicitly states that warfarin is contraindicated in women who are or may become pregnant 1
• Warfarin exposure during the first trimester (particularly between 6-12 weeks) causes embryopathy characterized by nasal hypoplasia and/or stippled epiphyses (chondrodysplasia punctata) with estimated incidence of 4-10% 2
• Central nervous system abnormalities can occur with warfarin exposure during any trimester, including dorsal midline dysplasia, agenesis of corpus callosum, and cerebellar atrophy 1
• Fetal cerebral hemorrhage can complicate labor and delivery, especially if forceps evacuation is necessary 2

Direct Oral Anticoagulants (DOACs)

• DOACs are not recommended during pregnancy due to concerns about safety 2
• Limited data exists regarding their use in pregnancy, but they should be avoided based on current guidelines 2

Safer Alternatives During Pregnancy

• Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are the preferred anticoagulants during pregnancy 2, 3
• These agents do not cross the placenta due to their high molecular weight and do not cause fetal bleeding or teratogenicity 2, 3
• LMWH is generally preferred over UFH due to practical advantages and lower risk of side effects such as heparin-induced thrombocytopenia and osteoporosis 3, 4

Special Considerations for Mechanical Heart Valves

• For pregnant women with mechanical heart valves, anticoagulation management is particularly challenging 2
• The European Society of Cardiology recommends that for pregnant patients with mechanical prostheses, therapeutic anticoagulation with LMWH or vitamin K antagonists (except during first trimester and beyond week 36) should be used 2
• When heparin is used during the first trimester in patients with mechanical heart valves, there is a higher risk of maternal thromboembolism and mortality compared to warfarin 2
• Some experts suggest using heparin in the first trimester and after week 36, with warfarin potentially used between weeks 12-36 if necessary for high-risk patients 2, 3

Practical Management

• For women requiring long-term warfarin therapy who are planning pregnancy, frequent pregnancy tests should be performed with substitution of heparin when pregnancy is achieved 2
• If warfarin is used during pregnancy (e.g., in high-risk mechanical valve patients), it must be discontinued and switched to heparin several weeks before delivery 2
• Vaginal delivery is contraindicated during vitamin K antagonist treatment due to risk of fetal intracranial bleeding 2
• The risks of any anticoagulation regimen during pregnancy should be clearly explained to patients 4, 5

Monitoring Considerations

• During pregnancy, the activated partial thromboplastin time (aPTT) response to heparin is often attenuated due to increased levels of factor VIII and fibrinogen 2
• Careful monitoring is essential when using anticoagulants during pregnancy to balance maternal thrombotic risk against fetal safety 3, 4