Management of abnormal uterine bleeding on anticoagulation: the patient-clinician perspective.

Bleeding is a well-recognized side effect of anticoagulant therapy, which is used to treat venous thromboembolism (VTE) in individuals of all ages, including those of female sex, who commonly experience VTE as a complication of hormonal therapies and/or pregnancy. Heavy menstrual bleeding (HMB) is also extremely common in reproductive-aged individuals of female sex. Despite these overlapping situations, relatively little attention has been paid to the impact of anticoagulant-associated HMB on treatment strategies and the patient experience. In this review, we summarize incidence and complications of HMB in anticoagulated individuals as well as management strategies for HMB in this population. We also address the patient experience, including the impact of HMB on quality of life and the impact of discontinuing hormonal therapies at the time of VTE diagnosis and anticoagulant initiation. We conclude by highlighting specific gaps related to the patient experience of anticoagulant-associated HMB in both the research and clinical settings.

Heavy menstrual bleeding in women on oral anticoagulants.

BACKGROUND: Although heavy menstrual bleeding (HMB) is a known complication of anticoagulant therapy, rates of HMB in users of the direct oral anticoagulants (OACs) apixaban and rivaroxaban are largely unknown. METHODS: We performed a retrospective cohort study of menstruating women prescribed rivaroxaban, apixaban and warfarin over a six-year period (2012-2018). The primary outcome was HMB requiring medical or surgical intervention. We used descriptive statistics and logistic regression to evaluate associations between OAC type, age, history of HMB, and the primary outcome. RESULTS: We identified 195 women of reproductive-age with a new therapeutic OAC prescription (62 on rivaroxaban, 54 on apixaban, 79 on warfarin). A minority (26/195, 13.3%) had a documented history of HMB, including 9 rivaroxaban users, 7 apixaban users and 10 warfarin users but most women (117/195, 60%) had no menstrual history documented. One third of subjects (64/195) required treatment for HMB within 6 months of starting OAC therapy. After controlling for a history of HMB, rivaroxaban users were 1.4 times more likely to require treatment as compared to users of other OACs. DISCUSSION: We found an association between rates of HMB necessitating medical or surgical intervention and rivaroxaban use. We also found that the majority of women did not have a documented menstrual history, suggesting that many providers do not inquire about menstrual bleeding when starting OAC therapy. Menstruating women, particularly those with a history of HMB, may be at increased risk for HMB necessitating medical treatment depending on the type of OAC used.

Abnormal uterine bleeding in users of rivaroxaban and apixaban.

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.

Hematopoietic Cell Transplantation for Myelofibrosis: the Dynamic International Prognostic Scoring System Plus Risk Predicts Post-Transplant Outcomes.

Hematopoietic cell transplantation (HCT) provides potentially curative treatment for patients with myelofibrosis (MF). HCT outcomes are associated with the Dynamic International Prognostic Scoring System (DIPSS) risk scores. In the present study we analyzed results in 233 patients to determine if the DIPSS plus classification, which adds cytogenetics, thrombocytopenia, and RBC transfusion dependence as risk factors, would better predict post-HCT outcomes than the original DIPSS. Multivariate analysis showed that each risk parameter incorporated into the DIPPS plus model contributed to its predictive power of overall mortality, relapse-free survival, and nonrelapse mortality. The 5-year overall survival (OS), relapse, and treatment-related mortality (TRM) rates for patients with low/intermediate-1 risk MF were 78%, 5%, and 20%, respectively. The 5-year OS, relapse, and TRM rates for patients with high-risk MF were 35%, 28%, and 40%, respectively. The HCT-specific comorbidity index of 3 or greater was associated with higher nonrelapse and overall mortality and reduced relapse-free survival. The relapse incidence was significantly increased in older patients (HR, 3.02; P = .0007). With a median follow-up of 8 years 124 patients (53%) were surviving. The components of the DIPSS plus classification still have prognostic relevance after adjustment by the DIPSS classification. This information should enhance our ability to advise patients when making decisions regarding timing of transplant.