Andrew M. Kaunitz, MD reviewing Martinelli I et al. Blood 2016 Mar 17.

Because use of combination estrogen­progestin contraceptives raises risk for venous thromboembolism (VTE), these methods are considered to be contraindicated in women with personal histories of VTE. Using data derived from a manufacturer­supported trial of the oral anticoagulant rivaroxaban versus subcutaneous enoxaparin (low­molecular­weight heparin) followed by Coumadin or another vitamin K antagonist (VKA), investigators assessed recurrent VTE and abnormal uterine bleeding (AUB) in 1888 women aged <60 (mean age, 41) stratified by use or nonuse of hormonal contraceptives. During the study period, 1413 participants did not use hormonal contraception and 475 did so (306 combination, 217 progestin­only).

Incidence of recurrent VTE in women who used hormonal contraception was 3.7% per year; in those who did not, incidence was 4.7% per year (adjusted hazard ratio, 0.56; 95% confidence interval, 0.23–1.39). VTE recurrence was similar among women using combination and progestin­only contraception. Among participants with an intact uterus, about one in five had AUB, with this proportion similar among users and nonusers of hormonal contraception. However, incidence of AUB was lower among women using progestin­only methods. Incidence of AUB leading to blood transfusion was 1.6% per year and 2.5% per year among women using and not using hormonal contraception, respectively. AUB necessitating transfusion was six times more common with rivaroxaban than enoxaparin/VKA. Almost half of women with AUB requiring transfusion had uterine fibroids, adenomyosis, or both conditions.


Unintended pregnancy among women with histories of VTE is a high-­risk condition; furthermore, VKAs are teratogens. Both points underscore the importance of these findings that, among women with VTE histories who are receiving anticoagulants, hormonal contraception does not increase recurrent VTE risk and that progestin contraceptives attenuate uterine bleeding. VKAs are known to cause heavy menstrual bleeding; in this study, the high prevalence of uterine pathology and the finding that rivaroxaban increased bleeding more than VKAs can help to inform the management of reproductive-­aged women requiring anticoagulation. Finally, women receiving a course of anticoagulation who are using combination contraceptives should discontinue these methods and consider alternatives before stopping anticoagulants.


Martinelli I et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

Blood 2016 Mar 17; 127:1417. (­2015­08­665927)      Abstract/FREE Full Text