Demographic and regional trends in aplastic anemia mortality among adults in the United States, 1999-2020: A retrospective study using CDC wonder data

Abstract Introduction: Global and historical data identify Aplastic Anemia as a high-risk disease with significant early mortality. Factors like bleeding risk posed by severe neutropenia and infection risk posed by thrombocytopenia have been recognized as primary factors influencing burden. Yet, the mortality burden among adults in the United States remains unexplored. We sought to address this gap by determining trends and disparities in Aplastic Anemia associated mortality among different demographic groups. Methods: Data on Aplastic Anemia-associated deaths from 1999 to 2020 were accessed from the CDC Wonder Multiple Cause of Death (MCD) database using the ICD-10 code: D61. We extracted mortality counts and age-adjusted mortality rates (AAMR) for individuals aged 25 and above. Analysis of trends in AAMR was done by calculating annual percentage change (APC) and average annual percent change (AAPC) using Joinpoint regression software. Results: A total of 108,280 Aplastic Anemia-related deaths occurred among adults in the US, with the overall AAMR rising from 2.51 in 1999 to 2.61 in 2020 with an AAPC of 0.1978. Between 1999 and 2002, a significant decline was observed (APC: -4.2394*) and a reversal in trend occurred between 2015 and 2020 (APC: 3.2469*). Overall AAMR in men was higher than that in women (2.81 vs. 1.9), but a declining trend was observed in the former (AAPC: -0.0664) in comparison to the mildly positive trend seen in the latter (AAPC: 0.2332). An upward trend in AAMR was observed in all age groups except those aged 35-44 years (AAPC: -0.3327) and 85 and above (AAPC: -0.6734*). The most significant rise was exhibited by the 55-64 age group (AAPC: 1.0773*). Among racial groups, the highest overall AAMR was seen in Non-Hispanic (NH) American Indians (2.55), followed by NH Blacks (2.48), NH Whites (2.26), Hispanics (2.05) and lastly, NH Asians (1.77). Slightly negative trends in AAMR were observed among NH Asians (AAPC: -0.6614) and NH Blacks (AAPC: -0.0956) whereas mild upward trends were seen in NH Whites (AAPC: 0.4232) and Hispanics (AAPC: 0.2832). The Midwest region had the higher overall AAMR (2.41) and the Northeast region had the lowest (1.97). Of particular note is the downward trend in AAMR reported in the Northeast (AAPC: -1.0057*) compared to the slightly increasing trends identified in other regions. Rural areas had elevated rates compared to Urban areas (2.62 vs. 2.2) but data demonstrated rising trends for both (Rural AAPC: 0.9892* vs. Urban AAPC: 0.1669). Considerable statewide variation was evident with highest AAMR seen in North Dakota (3.34), South Dakota (3.21) and West Virginia (3.12) and lowest seen in Louisiana (1.7), Massachusetts (1.69) and New York (1.49). Mortality burden was highest in inpatient facilities (60.44%). ConclusionOverall, a rise in Aplastic anemia-associated mortality was observed from 1999 to 2020. Disparities are evidenced by the increased AAMR in males, NH American Indians and the Midwest region. Targeted interventions like early diagnosis and equitable and timely access to treatments such as hematopoietic stem cell transplantation are necessitated to address and mitigate the disproportionate burden seen in these groups