Many patients receiving oral anticoagulation for venous thromboembolism (VTE) are in their reproductive years, but the potential for reproductive toxicity of direct oral anticoagulants (DOACs) in humans is not yet well established. A literature review evaluating pregnancy outcomes after DOAC exposure suggests DOACs have a lower risk of reproductive toxicity compared with vitamin-K antagonists (VKA) .
Dr Jan Beyer-Westendorf (UNI-Klinikum Carl Gustav Carus Medizinische Klinik I, Germany) pointed out that planned pregnancies in women on DOACs require a careful risk-benefit assessment, and that individualised decisions need to include patient perspective, preferences, and fears . DOACs are small molecules that can cross the placenta. Previously, an increased transfer of dabigatran, rivaroxaban, and apixaban to the foetal site of the placenta was shown in a human placental model. Thus, DOAC exposure during pregnancy should be minimised and switching to low-molecular-weight heparins (LMWH) is indicated when a pregnancy is diagnosed. Yet, DOACs are not strictly contraindicated in pregnancy: product information, for example of rivaroxaban, recommend using the agent with caution.
In 2016, Dr Beyer-Westendorf published a first case collection on DOAC exposure in pregnancy including 233 separate cases, of which 137 had reported outcomes. At that time, there was insufficient data to judge a possible embryotoxic risk of DOACs. The current data collection performed in 2020 included 593 separate cases. Most women had to take DOACs as prophylaxis or treatment for VTE. These cases yielded 316 known outcomes: 55.4% of the pregnancies ended with live birth and 21.8% with miscarriages. In 22.8% of cases, pregnancies were terminated electively. Only 3.8% of abnormalities were compatible with embryotoxicity. Reassuringly, no specific abnormality pattern emerged. “This is very different from warfarin, where abnormalities are more frequent and show a distinct embryotoxic pattern,” Dr Beyer-Westendorf explained.
Since 2016, there is a guideline for DOACs exposure in pregnancy . In case of a planned pregnancy, DOACS should be switched to an alternative anticoagulant pre-conceptually. In case of unintended pregnancy while on a DOAC, patients should discontinue DOACs immediately and switch to LMWH. However, inadvertent exposure to a DOAC is not sufficient ground for termination of pregnancy, and the guidelines recommend early obstetric review and foetal monitoring in the guideline. Dr Beyer-Westendorf recommended to re-assess the need for anticoagulation in all patients that plan a pregnancy. In some women, ASA may be an alternative. If a patient is concerned about the lack of DOAC safety data, she should switch to LMWH. If LMWH are not accepted, they should stay on DOAC until the pregnancy is confirmed and then switch to LMWH. “Do not counsel towards termination but advocate close monitoring of pregnancy instead,” Dr Beyer-Westendorf recommended considering the low risk of DOACs in early pregnancy.
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