What are the effects of anticoagulants (blood thinners) on conception?

From the Guidelines

Women taking anticoagulants who are planning pregnancy should switch to low molecular weight heparin (LMWH) before conception, as warfarin crosses the placenta and can cause birth defects, with a recommended daily dose of LMWH adjusted according to anti-Xa levels, as stated in the 2021 ACC/AHA guideline 1. When considering conception, it's essential to weigh the risks and benefits of anticoagulant therapy.

• Warfarin, a commonly used anticoagulant, poses significant risks to the fetus, including birth defects and fetal intracranial hemorrhage, especially if taken in doses >5 mg/d during the first trimester 1.
• In contrast, LMWH does not cross the placenta and is considered a safer alternative for women trying to conceive, with a lower risk of fetal complications 1.
• The American College of Cardiology/American Heart Association (ACC/AHA) guideline recommends that women taking warfarin switch to LMWH before planned delivery, and ideally before conception, to minimize the risk of fetal complications 1.
• The guideline also emphasizes the importance of counseling and shared decision-making between the woman and her physician to choose the best anticoagulation strategy, taking into account the woman's values and priorities 1.
• For women who require a warfarin dose >5 mg/d, replacing warfarin with dose-adjusted LMWH during the first trimester can reduce fetal loss, and switching back to warfarin for the second and third trimesters can achieve a reasonable balance between maternal safety and fetal safety 1. Key considerations for anticoagulant management in women planning pregnancy include:
• The need for close monitoring of anti-Xa levels and adjustment of LMWH doses to ensure effective anticoagulation and minimize the risk of maternal and fetal complications 1.
• The importance of coordinating care with the obstetrics and anesthesia teams to ensure safe delivery and minimize the risk of maternal bleeding and fetal complications 1.
• The potential risks and benefits of alternative anticoagulants, such as direct oral anticoagulants (DOACs), which are not recommended during pregnancy attempts due to limited data on their effects on conception and early pregnancy 1.

From the FDA Drug Label

Warfarin sodium tablets are contraindicated in women who are or may become pregnant because the drug passes through the placental barrier and may cause fatal hemorrhage to the fetus in utero. Furthermore, there have been reports of birth malformations in children born to mothers who have been treated with warfarin during pregnancy. Women of childbearing potential who are candidates for anticoagulant therapy should be carefully evaluated and the indications critically reviewed with the patient If the patient becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus, and the possibility of termination of the pregnancy should be discussed in light of those risks.

The effects of anticoagulants, such as warfarin, on conception are that they are contraindicated in pregnancy due to the risk of:

• Fatal hemorrhage to the fetus
• Birth malformations
• Spontaneous abortion and stillbirth
• Low birth weight and growth retardation It is recommended that women of childbearing potential who are candidates for anticoagulant therapy be carefully evaluated and the indications critically reviewed with the patient 2. Regarding heparin, while it does not have a direct contraindication for pregnancy, it can cause ovarian (corpus luteum) hemorrhage in women of reproductive age, which can be fatal if unrecognized 3.

From the Research

Effects of Anticoagulants on Conception

• The use of anticoagulants, such as heparin and oral anticoagulants, during pregnancy can have adverse effects on both the mother and the fetus 4.
• Heparin is considered safer for the fetus than oral anticoagulants, and is the preferred anticoagulant for the prophylaxis and treatment of venous thromboembolic disease in pregnant patients 4.
• Low-molecular-weight heparin (LMWH) has been shown to reduce the risk of preeclampsia and other placenta-mediated complications in high-risk women, particularly when started before 16 weeks' gestation 5.
• The combination of LMWH and low-dose aspirin has been found to be effective in preventing preeclampsia, preterm birth, and fetal growth restriction in high-risk pregnancies without thrombophilia 6.

Specific Anticoagulants and Their Effects

• LMWH has been shown to reduce the incidence of preeclampsia (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high-risk pregnant women without thrombophilia 6.
• The use of vitamin K antagonists (VKAs) throughout pregnancy has been compared to sequential anticoagulation (heparins in the first trimester and peripartum period and VKAs for the remainder of pregnancy) in women with mechanical heart valves, with no significant differences in maternal deaths, thromboembolic events, or hemorrhagic complications 7.
• The combination of LMWH and aspirin has been found to be no more effective than aspirin alone in reducing the risk of recurrent hypertensive disorders of pregnancy in women with antiphospholipid antibodies 8.

Pregnancy Outcomes and Anticoagulant Use

• The use of anticoagulants during pregnancy has been associated with a reduced risk of preeclampsia, small for gestational age, and perinatal death 5.
• However, the quality of evidence for these outcomes is generally low to moderate, due to the lack of blinding, imprecision, and inconsistency in the studies 5.
• Further research is needed to fully understand the effects of anticoagulants on conception and pregnancy outcomes, particularly in high-risk populations 5, 6.