Antenatal management of women who suffered a prior adverse pregnancy outcome or who have an inherited thrombophilia is not currently guided by a high level of scientific evidence (no well-conducted large multicenter randomized controlled trials [RCTs]). Should these women undergo a thrombophilia work-up and/or receive anticoagulation therapy? In the absence of such data, in general, 2 approaches can be considered: (1) follow the Hippocratic tenants and first do no harm (eg, do not screen or treat, given the absence of evidence of efficacy and the potential for harm) or (2) given the considerable risk of adverse pregnancy outcome in these women, consider a risk/benefit plus patient preference justification for screening and treatment. Appropriately so, American College of Obstetricians and Gynecologists guidelines promote a more conservative approach recommending against aggressive work-up or treatment. However, an argument that justifies screening and treatment can be made:
Women with a prior adverse pregnancy outcome (APO) or an inherited thrombophilia have a very high rate of APO (up to 26% have recurrent APO, approximately 6% have stillbirth). For this reason, a lower evidentiary threshold for efficacy is permissible. Despite the lack of high-quality level I data, observational data, results of small RCTs, biological plausibility, and expert opinion all provide some support for treatment benefit. Any potential for treatment benefit, however limited, may be acceptable to many women with poor obstetrical histories. Therefore, women should have the autonomy, after being informed by physicians, to choose this approach.
The actual risks and costs of anticoagulation are not out of perspective compared with other therapies (eg, infertility care) designed to result in favorable pregnancy outcome. The major risks of bleeding/hemorrhage are actually quite low.
Overtreatment of women with prior APO or inherited thrombophilias may improve perinatal survival by increasing the likelihood of maternal-fetal medicine subspecialty care, frequency of maternal-fetal evaluations, antenatal surveillance, and timed delivery.
In summary, it is quite amazing to me that we are having this same debate after so many years and still have no large scale RCTs to guide us. If you compare the editorial written by Dr Baha Sibai from the New England Journal of Medicine in 1999 to our current discussions, we have truly made little progress on this subject. Our patients deserve better evidence-based care.