Mortality patterns due to aplastic anemia in the United States: A retrospective analysis from 1999 to 2023

Abstract Introduction: Aplastic anemia (AA), a life-threatening bone marrow failure disorder with an incidence of 0.6-6.1 per million, carries significant mortality despite therapeutic advances. This study characterizes temporal trends and identifies demographic and geographic disparities in AA-related mortality across the United States from 1999 to 2023. Methods: Using CDC WONDER Multiple Cause of Death data (ICD- 10 code D 61), we calculated crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 people. Temporal trends were analyzed with Joinpoint regression to determine annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals. Results: Among 131,548 AA-related deaths from 1999 to 2023, AAMR increased significantly from 2. 51 in 1999 to 2. 85 in 2023 (AAPC: 0. 71%; 95% CI: 0. 08 to 1. 35, p = 0. 03). Striking disparities emerged: Males had persistently higher mortality than females (AAMR: 2. 89 vs. 1. 96), and Black individuals experienced the highest mortality among racial groups (AAMR: 2. 50), followed by White (2. 34), Hispanic/Latino (2. 10), American Indian/Alaska Native (2. 06), and Asian/Pacific Islander populations (1. 80). Geographically, the Midwest recorded the highest burden (AAMR 2.49), exceeding the South (2.40), West (2.35), and Northeast (2.01). State-level analysis identified clusters of elevated mortality in Minnesota, South Dakota, North Dakota, and Nebraska. Non-metropolitan areas demonstrated notably higher mortality than metropolitan regions (AAMR: 2.63 vs. 2.23). Conclusion: This national analysis reveals a concerning rise in AA mortality in the U. S. over 25 years, despite modern therapies, highlighting critical inequities across sex, racial, and geographic dimensions. The disproportionate burden among males, Black individuals, Midwestern residents, and rural populations underscores systemic gaps in specialized care, timely diagnosis, and treatment delivery. These findings necessitate targeted public health strategies addressing socioeconomic barriers, environmental determinants, and equitable expansion of hematology care infrastructure to mitigate AA-associated mortality.