Are Direct Oral Anticoagulants (DOACs) safe during pregnancy?

DOACs Are Not Safe During Pregnancy and Should Be Avoided

DOACs should not be used during pregnancy due to insufficient safety data, animal studies showing reproductive toxicity, and concerning human case reports of fetal abnormalities. 1, 2, 3

Immediate Management if Pregnancy Occurs on DOAC

If a woman becomes pregnant while taking a DOAC, discontinue it immediately and switch to low molecular weight heparin (LMWH). 1

• Stop the DOAC as soon as pregnancy is confirmed 1
• Initiate LMWH for continued anticoagulation 1
• Do not delay this switch—DOACs cross the placenta and have demonstrated embryotoxic potential 1

Evidence Against DOAC Safety in Pregnancy

Animal Studies Show Reproductive Toxicity

• Dabigatran: Causes fetal growth restriction, anomalies, and fetal mortality at 4-10 times human exposure levels 1, 2
• Rivaroxaban: Causes postimplantation loss, delayed ossification, hepatic abnormalities, and increased malformations at clinically relevant concentrations 1
• Edoxaban: Causes gallbladder anomalies and pregnancy loss at 50-65 times human doses 1
• Apixaban: While animal studies show less toxicity, the FDA label still recommends against use in pregnancy 3

Human Data Raises Serious Concerns

The largest retrospective cohort of 614 pregnancies with DOAC exposure (predominantly rivaroxaban) showed 4:

• Only 56% resulted in live births
• 22% ended in miscarriage
• 22% were electively terminated
• 4% had major birth defects potentially related to DOAC exposure (95% CI 2-6%)
• 6% showed any fetal abnormalities

A 2022 meta-analysis demonstrated higher rates of fetal loss and abnormalities with DOACs compared to LMWH 5. A 2018 systematic review found a 31% miscarriage rate and 4% rate of anomalies with rivaroxaban use 6.

DOACs Are Classified as Pregnancy Category C

Based on limited human data and animal studies showing adverse fetal effects, DOACs are considered Category C drugs—potential benefits may warrant use despite potential risks, but only in exceptional circumstances 1

Pre-Pregnancy Planning for Women Requiring Anticoagulation

Women of childbearing potential on DOACs must receive documented counseling about pregnancy avoidance and use effective contraception. 1

If pregnancy is desired, switch from DOAC to alternative anticoagulation pre-conceptually: 1

• Option 1: Switch to vitamin K antagonist (VKA), then transition to LMWH before 6 weeks gestation 1
• Option 2: Switch directly to LMWH (requires prolonged subcutaneous injections until pregnancy achieved) 1

Management After Inadvertent DOAC Exposure

Counseling About Pregnancy Continuation

Inadvertent DOAC exposure alone should not be considered medical grounds for pregnancy termination. 1

• Provide non-directive counseling about the limited available data 1
• Discuss the 4% risk of major birth defects potentially related to DOAC exposure 4
• Explain that most exposures (84%) were discontinued within first 2 months with variable outcomes 6

Intensive Fetal Monitoring Protocol

If pregnancy continues after DOAC exposure, implement comprehensive obstetric surveillance: 1

First trimester (as soon as possible):

• Early ultrasound to assess fetal viability 1
• Check for subchorionic or retroplacental bleeding 1

11-13 weeks + 6 days:

• Detailed first trimester scan by experienced sonologist 1

18-23 weeks (anomaly scan):

• Comprehensive anatomical survey by experienced sonologist 1
• Fetal echocardiogram to detect cardiac malformations 1
• Cervical length assessment for preterm delivery risk 1

If exposure extended beyond first trimester:

• Serial ultrasounds to monitor fetal growth and well-being 1
• Monitor for evidence of intracranial bleeding 1

Mandatory Reporting

Report all cases of DOAC exposure during pregnancy to: 1

• DOAC manufacturers 1
• Responsible health and regulatory authorities 1
• International ISTH registry 1

Postpartum and Breastfeeding

DOACs should not be used during breastfeeding due to absence of safety data. 1

• Animal studies show DOACs accumulate in milk at 30:1 milk-to-plasma ratio for apixaban 3
• In non-lactating postpartum women, carefully assess individual risk factors before initiating DOACs 1

Critical Pitfalls to Avoid

• Do not continue DOACs during pregnancy even if the patient has a strong indication for anticoagulation—LMWH is the safer alternative 1
• Do not assume all DOACs carry equal risk—most human data concerns rivaroxaban (82% of reported cases), with less information on other agents 4
• Do not recommend elective termination based solely on DOAC exposure—the absolute risk of major malformations is approximately 4%, not high enough to mandate termination 1, 4
• Do not use DOACs peripartum or during neuraxial anesthesia—risk of epidural/spinal hematoma 2, 3