May-June 2018, Volume 15, Issue 3
Management of Heavy Menstrual Bleeding on Anticoagulation
Published on: April 25, 2018
Boonyawat K, O'Brien SH, Bates SM. How I treat heavy menstrual bleeding associated with anticoagulants. Blood. 2017;130:2603-2609.
Heavy menstrual bleeding (HMB) is a well-known adverse effect of anticoagulant therapy. As women do not necessarily spontaneously report their menstrual bleeding patterns and physicians may not inquire about them, HMB may be missed during clinic visits, and potentially useful treatment options may therefore not be considered, discussed, and implemented.
In this context, the current publication by Dr. Kochawan Boonyawat and colleagues, while not presenting any original data, is a welcome summary of the present knowledge of anticoagulant-associated HMB. It should heighten awareness of the impact of anticoagulants on menstrual bleeding and existing treatment options, and supplement a previously published systematic review and expert panel opinion publication on the same topic.1
Dr. Boonyawat and colleagues cover key points with respect to definition and etiology of HMB: 1) The term menorrhagia has been discarded and replaced with heavy menstrual bleeding (HMB); 2) in a clinically meaningful way, HMB is defined as menstrual blood loss that interferes with a woman’s physical, social, emotional, and/or material quality of life; 3) HMB associated with anticoagulant use is common; 4) vitamin K antagonists significantly increase the duration of menstruation, flooding, passage of clots, and intermenstrual bleeding; 5) HMB seems to be more common with direct factor X inhibitors than with warfarin, but may be less common with dabigatran compared with warfarin; 6) although direct oral anticoagulants (DOACs) have not been directly compared with one another in clinical trials, prospective real-world data (of mostly rivaroxaban-treated patients) have suggested that HMB may be comparable for all factor Xa inhibitors.2 7) and based on an abstract-only publication, the lower dose of rivaroxaban (10 mg once daily, as used in the EINSTEIN CHOICE trial, compared with 20 mg once daily) leads to less menstrual flow length and intensity.3 Importantly, the authors summarize multiple options for treatment of HMB (Table). Progestin intrauterine devices (IUDs) can be used safely, and combined estrogen-progestin contraceptives are treatment options as long as reliable and full-dose anticoagulation is given. The effect of the anticoagulant is sufficient to overcome the incremental prothrombotic risk associated with the hormonal contraceptives. In some cases, a switch to a different anticoagulant can be considered or a reduced-dosed DOAC can be used (apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily) once the full-dose treatment period of three to six months for venous thromboembolism (VTE) has been completed. Finally, tranexamic acid can be considered.
Treatment Options for Heavy Menstrual Bleeding on Anticoagulants
|Progestin intrauterine device|
|Combined estrogen-progestin contraceptive|
|Endometrial ablation procedure (if no further pregnancies desired)|
|Tranexamic acid at times of menstrual flow|
|Decrease in anticoagulant drug dosing (rivaroxaban 10 mg once daily; apixaban 2.5 mg twice daily; lower target international normalized ratio)|
|Switch to a different anticoagulant*|
|Temporary interruption of anticoagulant treatment at time of menstrual bleeding|
|In the emergent massive bleeding situation:
- High-dose oral progestins
- Intravenous estrogens
*Insufficient data exist and there is no consensus amongst thrombosis and abnormal uterine bleeding experts in respect to the optimal anticoagulant drug in women with heavy menstrual bleeding on anticoagulation.1 Analyses of some of the phase III DOAC versus warfarin venous thromboembolism clinical trials and observational studies have not clearly identified one direct oral anticoagulant to lead to less heavy bleeding than another.2,5-10
The main management points in the female patient of childbearing age on anticoagulation for a VTE include specifically asking about the degree of menstrual bleeding during the clinic visit; having a low threshold to obtain a complete blood count (CBC) and a serum ferritin level; recommending a progestin IUD if the woman is considering having children in the future; discussing a progestin IUD or endometrial ablation procedure in the woman who does not plan to have further children; considering decreasing the DOAC dose after the initial three months of full-dose anticoagulation; and keeping in mind other potential treatment options such as a combined estrogen-progestin contraceptive (preferably a second-generation rather than third- or fourth-generation pill), higher-dose oral progestins as per gynecologic recommendations, and use of tranexamic acid.
Klok FA, Schreiber K, Stach K, et al. Oral contraception and menstrual bleeding during treatment of venous thromboembolism: Expert opinion versus current practice: combined results of a systematic review, expert panel opinion and an international survey. Thromb Res. 2017;153:101-107.
Beyer-Westendorf J, Michalski F, Tittl L, et al. Vaginal bleeding and heavy menstrual bleeding during direct oral anti-Xa inhibitor therapy. Thromb Haemost. 2016;115:1234-1236.
Boonyawat K, Lensing A, Prins M, et al. Menstrual bleeding patterns in women treated with rivaroxaban: Data from the EINSTEIN CHOICE trial. Abstract at ISTH meeting, Berlin, July 8-13, 2017. Abstract PB 1191.
Martinelli I, Lensing AW, Middeldorp S, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood. 2016;127:1417-1425.
Ferreira M, Barsam S, Patel JP, et al. Heavy menstrual bleeding on rivaroxaban. Br J Haematol. 2016;173:314-315.
Beyer-Westendorf J, Michalski F, Tittl L, et al. Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on oral anti-factor Xa inhibitor therapy: a case series. Lancet Haematol. 2016;3:e480-e488.
Brekelmans MP, Scheres LJ, Bleker SM, et al. Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin. Thromb Haemost. 2017;117:809-815.
Myers B, Webster A. Heavy menstrual bleeding on rivaroxaban – comparison with apixaban. Br J Haematol. 2017;176:833-835.
Bryk AH, Piróg M, Plens K, et al. Heavy menstrual bleeding in women treated with rivaroxaban and vitamin K antagonists and the risk of recurrent venous thromboembolism. Vascul Pharmacol. 2016;87:242-247.
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;136:749-753.
Conflict of Interests
Dr. Moll and Dr. Abajas indicated no relevant conflicts of interest.
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