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Review
. 2020 Dec 4;2020(1):538-541.
doi: 10.1182/hematology.2020000166.

Abnormal uterine bleeding in users of rivaroxaban and apixaban

Amanda E Jacobson-Kelly  1 , Bethany T Samuelson Bannow  2
Affiliations
Review

Abnormal uterine bleeding in users of rivaroxaban and apixaban

Amanda E Jacobson-Kelly et al. Hematology Am Soc Hematol Educ Program. .

Abstract

Up to two-thirds of menstruating women experience abnormal uterine bleeding (AUB) when treated with oral anticoagulants. However, the true prevalence of AUB for specific agents remains uncertain, as many of these episodes, while interfering significantly with quality of life and overall health, are not captured by definitions of major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) used in clinical trials. A 2017 systematic review determined that women taking rivaroxaban, but not edoxaban or apixaban, had a twofold higher risk of AUB than women taking warfarin. Since then, new data have become available from extension trials, cancer-associated venous thromboembolism trials, pediatric trials, and a few observational studies specifically examining AUB as an outcome. Reported rates of uterine CRNMB were low (around 1%) and similar for rivaroxaban and apixaban in all these studies, and no episodes of uterine bleeding meeting MB criteria were reported. Rates of AUB not meeting MB or CRNMB criteria were much higher, affecting up to 50% of women on rivaroxaban. Only 1 such study included women on apixaban, and no AUB was reported. In pediatric trials, 19% of girls experienced menorrhagia when treated with rivaroxaban. In conclusion, rates of uterine MB and CRNMB were low in all studies, but rates of other types of AUB not meeting these criteria ranged from 15.8% to 50%. We conclude that AUB is underreported due to the limitations of MB/CRNMB criteria despite its substantial impact on quality of life. We urge future investigators to include broader definitions of AUB to better capture the impact of this outcome in menstruating women treated with oral anticoagulants.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

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Graphical abstract
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References

    1. De Crem N, Peerlinck K, Vanassche T, et al. Abnormal uterine bleeding in VTE patients treated with rivaroxaban compared to vitamin K antagonists. Thromb Res. 2015;136(4):749-753. - PubMed
    1. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015;13(11):2119-2126. - PubMed
    1. Godin R, Marcoux V, Tagalakis V. Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism. Vascul Pharmacol. 2017;93-95:1-5. - PubMed
    1. Agnelli G, Buller HR, Cohen A, et al. ; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699-708. - PubMed
    1. Weitz JI, Lensing AWA, Prins MH, et al. ; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017;376(13):1211-1222. - PubMed

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