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Licensed Unlicensed Requires Authentication Published by De Gruyter January 24, 2022

Experience with direct oral anticoagulants in pregnancy – a systematic review

  • Ana Luísa Areia ORCID logo EMAIL logo and Anabela Mota-Pinto



The experience and use of the new direct oral anti coagulants (DOACs) in pregnancy is limited, but as they offer many practical advantages compared to low molecular weight heparin (LMWH), the pursue of their safety is challenging.


Systematic review of studies in which DOACs were used during pregnancy and the puerperal period (PROSPERO registry-CRD42021237688). Searches were performed on MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library databases, until July 2021 and secondary sources using the MeSH terms ‘pregnancy’, ‘pregnancy complications’, ‘venous thrombosis’, ‘congenital abnormalities’, ‘Factor Xa Inhibitors,’ and names of specific DOACs. Search was limited to human studies, with English or French as languages of report.


Literature search yielded 1,989 results which, after duplicate exclusion, resulted in 672 publications. Studies were then screened using the specified eligibility criteria described and studies that did not meet the criteria were excluded, resulting in 21 full text studies to an in-depth analysis and data extraction. Overall, 339 cases of DOACs usage during pregnancy were reported until now. The data demonstrated 56% live births but a miscarriage rate of 22.2% and an elective termination of pregnancy in 21.8%; fetal abnormalities related to DOACs occurred in 3.6%. Our meta-analysis displayed a higher rate of fetal loss and fetal abnormalities with DOACs use compared to LMWH, notwithstanding similar bleeding complications.


The current information available for the 339 cases herein reported does not allow a conclusion that DOACs can be safely used in pregnancy.

Corresponding author: Ana Luísa Areia, MD, PhD, Obstetrics Department, Centro Hospitalar e Universitário de Coimbra, Avenida Bissaya Barreto, 101-2B, 3000-076, Coimbra, Portugal; and Centre of Investigation in Environment, Genetics and Oncobiology (Cimago), Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Phone: +351 917212222, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. The lead author affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted and that allows full publication.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2021-09-06
Accepted: 2022-01-11
Published Online: 2022-01-24
Published in Print: 2022-05-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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