The extensive use of direct anticoagulants (DOACs) indefinitely places us in front of populations that have been excluded from registration studies or, as in the case of pregnant women, will never be able to participate in randomized trials on oral anticoagulants.
If it is difficult to prescribe a DOAC to a pregnant woman, given the frequent suspension of estrogen-progestogen therapy, we could find ourselves faced with a patient who discovers that she is pregnant while on therapy with DOACs.
What to advise to our patient? What is the risk of DOAC exposure in the first quarter?
The indications on the subject were strengthened by a retrospective study published in December 2020 in Lancet Haematology. The fetal consequences of 600 pregnant women exposed for nearly two months to DOAC, predominantly (85%) rivaroxaban, were analyzed. Information on the outcome of pregnancy was available for about half of the women. In 42% of these pregnancies, the conclusion was a spontaneous or induced abortion with the presence of fetal anomalies (6%) and major congenital defects (4%) potentially correlated with the effect of DOACs.
However, the statistical significance of the results was very limited, so much so that it did not lead to changes to the 2016 ISTH guidelines, which advise against preventive abortion for patients exposed to anticoagulants during pregnancy, while recommending close surveillance.
A new recent work, with similar numbers to the previous one, arrives at similar results and confirms that the use of DOACs in pregnancy does not appear safe. The meta-analysis of the published works highlights how, compared to pregnancies exposed only to LMWH, in the face of similar bleeding complications, the risk of complications (abortion and fetal anomalies) appears higher.
A study comparing DOAC and warfarin in pregnancy appears to show fewer birth defects with DOACs (7.4% vs 10.8%), with no specific DOAC defect and similar abortion rates to the general population.
Current recommendations for DOAC patients planning to become pregnant are to switch to LMWH.
For patients with unplanned pregnancy exposed to DOAC, the recommendation is to switch to LMWH when they discover they are pregnant, but not to terminate the pregnancy based on concern for fetal malformations as exposure is for a relatively short period.
Education and advice on the possible risks of pregnancy in women of childbearing age who take DOACs are essential.