What is the risk of hemorrhagic complications associated with the use of anticoagulants (blood thinners) during pregnancy?

From the Guidelines

The use of anticoagulants during pregnancy carries a significant risk of hemorrhagic complications, with low molecular weight heparins (LMWHs) being preferred due to their lower bleeding risk compared to warfarin, which poses significant fetal risks. The risk of major bleeding with prophylactic LMWH is approximately 0.5-1%, increasing to 2-3% with therapeutic dosing, as noted in the 2020 ACC/AHA guideline for the management of patients with valvular heart disease 1. Specific concerns include antepartum hemorrhage, postpartum hemorrhage (particularly within 24 hours of delivery), and wound hematomas following cesarean section.

To minimize these risks, LMWH should be discontinued 24 hours before planned delivery or induction, and regional anesthesia should be delayed until 12 hours after prophylactic doses or 24 hours after therapeutic doses. Unfractionated heparin has a shorter half-life (making it useful when delivery is imminent) but requires more frequent monitoring and carries a higher risk of heparin-induced thrombocytopenia, as discussed in the 2020 ACC/AHA guideline 1. Postpartum, LMWH can typically be resumed 6-12 hours after vaginal delivery or 12-24 hours after cesarean section, assuming adequate hemostasis.

Some key points to consider when using anticoagulants during pregnancy include:

• The risk of valve thrombosis and maternal death is high in pregnant women with mechanical heart valves, with a maternal mortality rate of >1% 1
• Warfarin is the most effective anticoagulant at preventing thrombotic complications, but it crosses the placenta and can cause miscarriage, spontaneous abortion, warfarin embryopathy, or fetal intracranial hemorrhage 1
• LMWH is not teratogenic, but women with mechanical heart valves on LMWH are at increased risk of thrombotic events, particularly when LMWH is improperly dosed, monitored, or administered 1
• Regular monitoring of platelet counts, especially in the first two weeks of therapy, is recommended to detect potential heparin-induced complications 1.

Overall, the management of anticoagulation during pregnancy requires careful consideration of the risks and benefits of different anticoagulant strategies, with a focus on minimizing the risk of hemorrhagic complications while preventing thrombotic events.

From the FDA Drug Label

There are risks to the mother associated with untreated venous thromboembolism in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants Use of anticoagulants, including fondaparinux sodium, may increase the risk of bleeding in the fetus and neonate. Fondaparinux sodium use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas Use of anticoagulants, including dabigatran etexilate capsules, may increase the risk of bleeding in the fetus and neonate. Dabigatran etexilate capsules use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas

The risk of hemorrhagic complications associated with the use of anticoagulants during pregnancy includes:

• Bleeding in the fetus and neonate
• Epidural or spinal hematomas during labor or delivery in women receiving neuraxial anesthesia
• Excess vaginal/uterine bleeding close to parturition These risks are associated with the use of anticoagulants, including fondaparinux sodium 2 and dabigatran etexilate capsules 3.

From the Research

Risk of Hemorrhagic Complications

The use of anticoagulants during pregnancy is associated with a risk of hemorrhagic complications.

• The risk of antepartum bleeding with prophylactic dosing of low-molecular-weight heparin (LMWH) is 0.5% and the risk of postpartum hemorrhage is 1% 4.
• With treatment dosing, the risk of antepartum bleeding is 1.5% and the risk of postpartum hemorrhage is 2% 4.
• A systematic review and meta-analysis found that the pooled prevalence of bleeding episodes per pregnancy across anticoagulant regimens was 0.13 (95% confidence interval [CI]: 0.09-0.18) 5.
• The combination of unfractionated heparin (UFH) and vitamin K antagonist (VKA) and single VKA therapy showed the lowest risk of bleeding (8 and 12%) 5.
• The highest risk of bleeding was found in women receiving a combination of low-molecular-weight-heparin (LMWH) and VKA (33%) or mono-therapy with LMWH (22%) 5.

Factors Influencing Risk

The risk of hemorrhagic complications may be influenced by several factors, including:

• The type and dose of anticoagulant used 4, 5.
• The presence of maternal comorbid conditions 6.
• The mode of delivery, although no difference in bleeding was found between caesarean section versus vaginal delivery 5.
• The use of vitamin K antagonists throughout pregnancy, which may be associated with a lower risk of bleeding 7.