Reproductive issues in women on direct oral anticoagulants

Abstract

Direct oral anticoagulants (DOACs) are replacing warfarin and other vitamin K antagonists for a wide range of indications. Advantages of DOAC therapy are fewer food and drug interactions and fixed dosing without routine laboratory monitoring, making DOACs the perfect choice especially for younger patients, in whom the main indication for anticoagulation is prevention and treatment of venous thromboembolism (VTE). Although DOACs are safer and much more convenient than other anticoagulant alternatives, their profile may have drawbacks, especially for younger female patients in whom reproductive issues need special considerations. These may include the issue of heavy menstrual bleeding (HMB) during anticoagulant therapy, the embryotoxicity risk from inadvertent DOAC exposure during pregnancy, and the prevention or planning of pregnancies during DOAC therapy. This review summarizes the most relevant evidence in this increasingly important field of women’s health.

How do anticoagulants impact menstrual bleeding and quality of life? - The PERIOD study

“…The mechanism behind the HMB observed with DOACs is not well understood; whether it is simply anticoagulation causing this or whether it is related to a mechanism at a molecular level is yet to be determined. Beyer-Westendorf and Marten suggest that increased bleeding observed with factor Xa inhibitors could be having a direct impact on coagulation factors or other proteins in the uterine wall [ 35 ]. They suggest that factor Xa inhibitors maybe synergistically acting with physiological anticoagulants required for shedding blood and endometrium cells during menstrual bleeding.…”

Serum fat-soluble vitamins and the menstrual cycle in women of childbearing age

“…In the context of the female reproductive system, vitamin K antagonists were reported to increase the risk of heavy menstrual bleeding. 42 In addition, vitamin K was reported to reduce menstrual pain and relieve nausea during pregnancy. 43 The main molecular pathway of vitamin K, PXR transcriptional activation, is present in the tissue involved in the reproductive system.…”

Management of heavy menstrual bleeding in women on long term anticoagulants

“…Also, it takes time and requires frequent monitoring before achieving the target INR. 2 Direct oral anticoagulants are the preferred choice instead. They act rapidly following administration and on stopping the drug the anticoagulant action wears off rapidly.…”

“…Also, it may have teratogenic effects in the fetus if the woman conceives during treatment. 2 Various theories have been put forth for the increase in menstrual blood loss in women on anticoagulation. It can result from direct action of these drugs on the coagulation factors or it can also alter the proteins in the myometrium DOI: https://dx.doi.org/10.18203/2320-1770.ijrcog20234102 Department of Obstetrics and Gynaecology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India and endometrium responsible for normal menstruation.…”