Mortality patterns and geographic variation in acquired hemophilia A among Medicare beneficiaries in the United States

Abstract Acquired hemophilia A (AHA) is a rare but life-threatening autoimmune bleeding disorder caused by autoantibodies against factor VIII. It presents with spontaneous bleeding in individuals without prior history of bleeding and carries a mortality rate of up to 21%. While older age and comorbidities are known risk factors for mortality, little is known about the impact of race, ethnicity and geographic region on survival. Notably, contemporary U.S. population-based studies evaluating these disparities are lacking. This preliminary national analysis explores demographic and geographic patterns in AHA mortality among Medicare beneficiaries. We conducted a retrospective cohort study of Medicare beneficiaries diagnosed with AHA between 2016 and 2020, defined by ≥2 diagnostic claims for AHA (ICD-10: D68.311) at least 30 days apart, excluding individuals with diagnosis of congenital bleeding disorders, von Willebrand disease, platelet or other bleeding disorders. Eligible patients had ≥6 months of continuous Medicare Parts A and B enrollment before and after diagnosis and complete demographic data. We followed patients from the date of AHA diagnosis until death, disenrollment, or the end of the study period (December 31, 2020). The primary endpoint was all-cause mortality, identified through the National Death Index. Cox proportional hazards models estimated unadjusted and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs), with race/ethnicity as the primary exposure of interest, adjusting for age, sex, comorbidity index, cancer, and geographic region. The history of cancer was assessed separately from the Charlson comorbidity index. Among 597 individuals with AHA, the median age at diagnosis was 75 years (SD: 11.5). Over half (51.8%) were female. A majority (80.4%) were Non-Hispanic White, 12.9% were Non-Hispanic Black, and 6.7% were Other. At diagnosis, 51.4% had a Charlson comorbidity index ≥2, and 8.5% had a cancer diagnosis. Over a mean follow-up duration of 2.6 years per patient, 129 patients (21.6%) died, with a mean age at death of 82.3 years (SD: 10.4). Mortality statistically significantly increased with age: compared to patients under 65, those aged 75-84 had an aHR of 2.13 (95% CI: 1.09-4.17), and those ≥85 had an aHR of 4.47 (95% CI: 2.25-8.84). Non-Hispanic Black patients had a non-significantly higher risk compared to Non-Hispanic White patients (aHR: 1.51; 95% CI: 0.88-2.58). A Charlson index ≥2 was associated with increased risk (aHR: 3.59; 95% CI: 2.15-5.97). A history of malignancies was also strongly associated with higher mortality (aHR 3.2, 95% CI: 2.11-4.87). Compared to the Northeast, patients in the West had significantly lower mortality (aHR: 0.31; 95% CI: 0.14-0.66). In this preliminary analysis of a national Medicare cohort with AHA, mortality remained high, particularly among older adults, patients with comorbidities, and those with cancer. Significant geographic variation in mortality was observed, with notably lower risk in the Western U.S., suggesting potential regional differences in diagnosis, access to care, or treatment patterns. Although Non-Hispanic Black patients had higher mortality, this difference was not statistically significant. These findings highlight the need for future research on healthcare equity and regional variation in outcomes for patients with AHA.