Rising sepsis-related mortality in aplastic anemia: A u.S. population-based analysis of temporal trends, disparities, and forecasts through 2030

Abstract Background: Patients with aplastic anemia (AA) are at increased risk of sepsis-related mortality due to underlying immunosuppression and bone marrow failure. Despite advances in treatment, sepsis remains a leading cause of death in this population. This study analyzes trends in sepsis-related mortality among AA patients in the U.S. from 1999 to 2023, with a focus on disparities by sex, race/ethnicity, geographic region, and urbanization status, and forecasts mortality trends through 2030. Methods: Age-adjusted mortality rates (AAMR) were calculated using national mortality data from the CDC WONDER database. Records were filtered to include deaths with ICD-10 code D61 (Aplastic Anemia) and ICD-10 code A41 (Sepsis) listed among the multiple causes of death. Temporal trends were identified using Joinpoint regression analysis, and future mortality rates were projected using ARIMA modeling. Stratified analyses were performed by sex, census region, state, race/ethnicity, and level of urbanization. Statistical significance was determined at a threshold of p < 0.05. Results: From 1999 to 2023, a total of 20,436 sepsis-related deaths occurred among AA patients. The AAMR initially declined from 19.1 (95% CI: 17.6–20.6) in 1999 to 16.3 (95% CI: 15.0–17.6) in 2001 but rose to 23.0 (95% CI: 21.8–24.3) by 2023. Males consistently exhibited higher mortality rates than females, with rates of 27.9 and 19.3, respectively, in 2023. Marked geographic disparities were observed, with the South recording the highest AAMR (24.9 in 2023), and states such as Kentucky (27.1) and Texas (26.1) exceeding the national average. Racial and ethnic analyses revealed persistently elevated mortality among Black individuals (25.8 in 2023), while Asian/Pacific Islanders experienced early declines followed by later increases. Urban-rural trends varied, with micropolitan areas peaking at an AMR of 23.8 (95% CI: 19.5–28.1) in 2020. Forecasts for 2021–2030 project stable but uncertain mortality trends, with an estimated AAMR of 19.5 (95% CI: 11.38–27.22) by 2030. Conclusion: Sepsis-related mortality among AA patients has increased significantly since the early 2000s, with pronounced disparities by sex, race, and geographic regions. The sustained rise, particularly among males and in Southern states highlights critical gaps in prevention and clinical management. Projections indicate no near-term improvement, emphasizing the urgent need for targeted interventions in high-risk populations.