Experience with direct oral anticoagulants in pregnancy – a systematic review
-
Ana Luísa Areia
und
Anabela Mota-Pinto
Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusions
The current information available for the 339 cases herein reported does not allow a conclusion that DOACs can be safely used in pregnancy.
-
Research funding: None declared.
-
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.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: Not applicable.
References
1. Lameijer, H, Aalberts, JJJ, van Veldhuisen, DJ, Meijer, K, Pieper, PG. Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review. Thromb Res 2018;169:123–7. https://doi.org/10.1016/j.thromres.2018.07.022.Suche in Google Scholar
2. Jacobson, B, Rambiritch, V, Paek, D, Sayre, T, Naidoo, P, Shan, J, et al.. Safety and efficacy of enoxaparin in pregnancy: a systematic review and meta-analysis. Adv Ther 2020;37:27–40. https://doi.org/10.1007/s12325-019-01124-z.Suche in Google Scholar
3. Greer, IA, Nelson-Piercy, C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005;106:401–7. https://doi.org/10.1182/blood-2005-02-0626.Suche in Google Scholar
4. Alban, S. Adverse effects of heparin. Handb Exp Pharmacol 2012:211–63. https://doi.org/10.1007/978-3-642-23056-1_10.Suche in Google Scholar
5. RCOG. Thrombosis and embolism during pregnancy and the puerperium, reducing the risk; 2019. Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37b.pdf.Suche in Google Scholar
6. Tang, AW, Greer, I. A systematic review on the use of new anticoagulants in pregnancy. Obstet Med 2013;6:64–71. https://doi.org/10.1177/1753495x12472642.Suche in Google Scholar
7. Hoeltzenbein, M, Beck, E, Meixner, K, Schaefer, C, Kreutz, R. Pregnancy outcome after exposure to the novel oral anticoagulant rivaroxaban in women at suspected risk for thromboembolic events: a case series from the German Embryotox Pharmacovigilance Centre. Clin Res Cardiol 2016;105:117–26. https://doi.org/10.1007/s00392-015-0893-5.Suche in Google Scholar
8. Konigsbrugge, O, Langer, M, Hayde, M, Ay, C, Pabinger, I. Oral anticoagulation with rivaroxaban during pregnancy: a case report. Thromb Haemostasis 2014;112:1323–4. https://doi.org/10.1160/th14-04-0393.Suche in Google Scholar
9. Myers, B, Neal, R, Myers, O, Ruparelia, M. Unplanned pregnancy on a direct oral anticoagulant (Rivaroxaban): a warning. Obstet Med 2016;9:40–2. https://doi.org/10.1177/1753495x15621814.Suche in Google Scholar
10. Beyer-Westendorf, J, Tittl, L, Bistervels, I, Middeldorp, S, Schaefer, C, Paulus, W, et al.. Safety of direct oral anticoagulant exposure during pregnancy: a retrospective cohort study. Lancet Haematol 2020;7:e884–91. https://doi.org/10.1016/s2352-3026(20)30327-6.Suche in Google Scholar
11. Rudd, KM, Winans, AR, Panneerselvam, N. Possible rivaroxaban failure during the postpartum period. Pharmacotherapy 2015;35:e164–8. https://doi.org/10.1002/phar.1662.Suche in Google Scholar
12. Vause, S, Clarke, B, Tower, CL, Hay, C, Knight, M. Pregnancy outcomes in women with mechanical prosthetic heart valves: a prospective descriptive population based study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system. BJOG 2017;124:1411–9. https://doi.org/10.1111/1471-0528.14478.Suche in Google Scholar
13. Komori, M, Hayata, E, Nakata, M, Yuzawa, H, Oji, A, Morita, M. Apixaban therapy in a pregnant woman with heparin-induced thrombocytopenia and venous thromboembolic events caused by congenital antithrombin deficiency: a case report. Case Rep Womens Health 2020;27:e00200. https://doi.org/10.1016/j.crwh.2020.e00200.Suche in Google Scholar
14. Vauzelle, C. Direct oral anticoagulants and pregnancy. Gynecol Obstet Fertil Senol 2021;49:301–3. https://doi.org/10.1016/j.gofs.2021.01.016.Suche in Google Scholar
15. Sessa, M, Mascolo, A, Callreus, T, Capuano, A, Rossi, F, Andersen, M. Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase((R)). Sci Rep 2019;9:7236. https://doi.org/10.1038/s41598-019-43715-4.Suche in Google Scholar
16. Beyer-Westendorf, J, Michalski, F, Tittl, L, Middeldorp, S, Cohen, H, Abdul Kadir, R, et al.. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting. Thromb Haemostasis 2016;116:651–8. https://doi.org/10.1160/TH16-04-0305.Suche in Google Scholar
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2021-0457).
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- WAPM Guideline
- The use of antenatal corticosteroids for fetal maturation: clinical practice guideline by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine foundation
- Corner of Academy
- Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of the late preterm delivery regardless of the membrane status
- Original Articles – Obstetrics
- Comparison of cardiac morphology and function in small for gestational age fetuses and fetuses with late-onset fetal growth retardation
- Effect of SARS-CoV-2 infection on fetal umbilical vein flow and cardiac function: a prospective study
- One year into the SARS-CoV-2 pandemic: perinatal outcome and data on the transmission of 116 pregnant women
- Adverse perinatal outcomes of chlamydia infections: an ongoing challenge
- Pregnancy outcomes with differences in grain consumption: a randomized controlled trial
- Who needs prenatal counselling with a pediatric surgeon? Experience from a large tertiary care university hospital
- To evaluate the role of placental human papilloma virus (HPV) infection as a risk factor for spontaneous preterm birth: a prospective case control study
- Placental characteristics of selective intrauterine growth restriction with changing patterns in umbilical artery Doppler flow in monochorionic diamniotic twins
- Association between cesarean section rate and maternal age in twin pregnancies
- Maternal and neonatal outcomes associated with delivery techniques for impacted fetal head at cesarean section: a systematic review and meta-analysis
- Experience with direct oral anticoagulants in pregnancy – a systematic review
- Nasal bone in fetal aneuploidy risk assessment: are they independent markers in the first and second trimesters?
- Effects of music on sleep quality and comfort levels of pregnant women
- Original Articles – Fetus
- Rarity of fetal cells in exocervical samples for noninvasive prenatal diagnosis
- Original Articles – Neonates
- Effects of oral stimulation with breast milk in preterm infants oral feeding: a randomized clinical trial
- Perinatal factors associated with admission to neonatal intensive care unit following cesarean delivery in Kano, northern Nigeria
- Letter to the Editor
- Intrapartal fetal decapitation after shoulder dystocia – a forensically acceptable or unacceptable complication?
Artikel in diesem Heft
- Frontmatter
- WAPM Guideline
- The use of antenatal corticosteroids for fetal maturation: clinical practice guideline by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine foundation
- Corner of Academy
- Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of the late preterm delivery regardless of the membrane status
- Original Articles – Obstetrics
- Comparison of cardiac morphology and function in small for gestational age fetuses and fetuses with late-onset fetal growth retardation
- Effect of SARS-CoV-2 infection on fetal umbilical vein flow and cardiac function: a prospective study
- One year into the SARS-CoV-2 pandemic: perinatal outcome and data on the transmission of 116 pregnant women
- Adverse perinatal outcomes of chlamydia infections: an ongoing challenge
- Pregnancy outcomes with differences in grain consumption: a randomized controlled trial
- Who needs prenatal counselling with a pediatric surgeon? Experience from a large tertiary care university hospital
- To evaluate the role of placental human papilloma virus (HPV) infection as a risk factor for spontaneous preterm birth: a prospective case control study
- Placental characteristics of selective intrauterine growth restriction with changing patterns in umbilical artery Doppler flow in monochorionic diamniotic twins
- Association between cesarean section rate and maternal age in twin pregnancies
- Maternal and neonatal outcomes associated with delivery techniques for impacted fetal head at cesarean section: a systematic review and meta-analysis
- Experience with direct oral anticoagulants in pregnancy – a systematic review
- Nasal bone in fetal aneuploidy risk assessment: are they independent markers in the first and second trimesters?
- Effects of music on sleep quality and comfort levels of pregnant women
- Original Articles – Fetus
- Rarity of fetal cells in exocervical samples for noninvasive prenatal diagnosis
- Original Articles – Neonates
- Effects of oral stimulation with breast milk in preterm infants oral feeding: a randomized clinical trial
- Perinatal factors associated with admission to neonatal intensive care unit following cesarean delivery in Kano, northern Nigeria
- Letter to the Editor
- Intrapartal fetal decapitation after shoulder dystocia – a forensically acceptable or unacceptable complication?
