A dangerous convergence: Long-term mortality trends in aplastic anemia and sepsis (1999-2023)

Abstract Background: Aplastic anemia (AA), a rare hematologic disorder characterized by pancytopenia and bone marrow failure, poses a high risk for opportunistic infections such as sepsis. The combination of these two conditions significantly increases mortality, yet national trends involving both have not been well characterized. This study analyzes 25-year mortality trends in U.S. deaths attributed to both AA and sepsis, with a focus on demographic and geographic disparities. Methods: Data from the CDC WONDER database (1999-2023) were retrospectively analyzed to calculate age-adjusted mortality rates (AAMRs) per 100,000 persons. Trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC), stratified by race/ethnicity. Results: A total of 140,846 AA-related deaths were recorded between 1999 and 2023. The national AAMR increased from 2.23 in 1999 to 3.33 in 2023 (mean AAMR: 2.478). The overall trend showed three distinct phases: a modest rise from 1999-2018 (APC 0.91, p<0.000001), a significant spike from 2018-2021 (APC 12.34, p=0.0008), and a subsequent nonsignificant decline from 2021-2023 (APC -2.93, p=0.266). By sex, males had higher AAMRs (2.76) than females (2.29), with AAPCs of 2.00 and 1.89, respectively (both p<0.05). Racially, African American individuals had the highest AAMR (4.85), followed by Asians (2.32) and Non-Hispanic Whites (2.24), with a significantly increasing trend noted in White populations (AAPC 2.43). By age, older adults exhibited the highest AAMR (9.36), followed by middle-aged (1.51) and young adults (0.28), with the middle-aged group showing the most significant upward trend (AAPC 2.81). Regionally, the South had the highest AAMR (2.85), while the West exhibited the most significant increase over time (AAPC 3.05). State-level analysis revealed widening disparities. In 1999, Idaho had the lowest AAMR (1.09) and the District of Columbia the highest (5.25). By 2018, Maine had the lowest AAMR (0.65), and South Carolina the highest (5.98), reflecting evolving geographic inequities. Conclusion: Co-mortality from aplastic anemia and sepsis is rising and reveals stark disparities by race, age, and geography. The sharp increase post-2018, coupled with elevated rates in African Americans individuals, older adults, and the South, underscores the need for enhanced infection surveillance and tailored hematologic care.