Heavy Menstrual Bleeding in Adolescents on Direct Oral Anticoagulants

Background Direct oral anticoagulants (DOACs) - Dabigatran, Rivaroxaban, and Apixaban - are increasingly being used in the pediatric and adolescent population. DOACs have been shown to increase the likelihood of heavy menstrual bleeding (HMB) in adult women of childbearing age, when compared to vitamin K antagonists or low molecular weight heparins (LMWH). There are limited data regarding the prevalence of HMB in the adolescent population on DOACs. Pivotal trials leading up to the approval of DOACs in the adolescent and pediatric populations also failed to prespecify prospective analyses on the impact of DOACs on HMB. The effect of HMB and its treatment burden can contribute to the compliance rates of DOACs in this population, adding to the recurrence rates of venous thromboembolism. Our study aims to assess the rate of HMB with DOAC use in adolescents by comparing the rate of HMB and its associated healthcare burden to patients on other anticoagulants. Methods This is a retrospective cohort study conducted with deidentified data obtained from the Pediatric Health Information System (PHIS) database after IRB approval. The PHIS is a comparative database with clinical and resource utilization data for inpatient, ambulatory surgery, ED, and observation unit encounters from more than 49 children's hospitals. ICD-10 codes were used to query the data for pediatric patients between the ages of 9-18 years on anticoagulant therapy from January 2020-December 2022. DOAC group was defined as patients on Rivaroxaban, Dabigatran, or Apixaban at any point in their care. The control group was defined as patients on anticoagulants other than DOACs, such as LMWH, unfractionated heparin, coumadin, and bivalirudin. Data extracted included any episode of HMB (diagnosis codes for abnormal uterine bleeding, dysfunctional uterine bleeding, menorrhagia, or heavy menstrual bleeding), risk factors for HMB other than anticoagulants, and healthcare utilization data for HMB such as number of ED visits, hospital admission and length of stay, and ICU admission. For the Descriptive statistics, demographics and clinical characteristics of the patients were described using median and interquartile range (25th percentile, 75th percentile) for continuous variables, and frequency and percentages for categorical variables, as appropriate. Control group was matched to the DOAC group by propensity score matching using nearest method with the ratio 1:5 to generate the similar pairwise comparison.