Trends and Disparities in Autoimmune Hemolytic Anemia-Related Mortality in the United States from 1999 to 2020: Insights from the CDC Wonder Database
Authors: Shahzad Moazzam , Ahmad Eeman , Ahmed Shahzaib , Akram Umar , Bilal Sardar Muhammad , Tuz Zahra Fatima , Iqbal Qamar , Mushtaq Muhammad Umair , Jaglal Michael V. 
Published: December 2024

Introduction: Autoimmune hemolytic anemia (AIHA) is an acquired condition characterized by hemolysis due to autoantibodies against red blood cell antigens. AIHA can be categorized as primary, when the underlying cause has not been demonstrated, and secondary, when the hemolysis is caused due to autoantibodies related to autoimmune diseases, lymphoproliferative diseases, infections, solid tumors or solid organ transplantation. Another form of secondary AIHA is drug-related AIHA, in which hemolysis is driven by the intake of certain drugs including antibiotics, antiviral drugs, and chemotherapeutic drugs. Mortality due to AIHA is estimated to be 10%; thus, there is a need to investigate the trends and disparities in AIHA-related mortality.
Methods: Data for AIHA-related deaths in the United States (US) was extracted from the CDC Wide-ranging ONline Data for Epidemiologic Research (WONDER) database from 1999 to 2020. The ICD-10 codes D59.0 (drug-induced AIHA) and D59.1 (other AIHAs) were used to extract age-adjusted mortality rates (AAMR) per 100,000 population. Changes in AAMR were observed through annual percentage change (APC) which was calculated via Joinpoint regression using the Joinpoint Regression Program (V 5.1.0, National Cancer Institute).
Results: From 1999 to 2020, a total of 7,015 AIHA-related deaths occurred in the US. A steep decrease in the AAMR was observed from 1999 to 2006 (APC: -5.32), after which the decline in the AAMR decreased until 2020 (APC: -0.39). The overall AAMR was a bit higher in males (0.10) than in females (0.09). A steady decrease in the AAMR for males was observed from 1999 to 2020 (APC: -1.45). On the other hand, the AAMR for females initially decreased from 1999 to 2005 (APC: -5.68), after which the APC decreased for the time period from 2005 to 2020 (APC: -0.87). Upon stratification by urbanization, non-metropolitan areas were observed to have a higher overall AAMR (0.091) in comparison to metropolitan areas (0.085) from 1999 to 2020. The AAMR for nonmetropolitan areas decreased consistently from 1999 to 2020 (APC: -1.13), whereas that for metropolitan areas decreased only till 2009 (APC: -4.65). Subsequently, the AAMR for metropolitan areas increased from 2009 to 2020 (APC: 0.62). Further variations in mortality trends across geographical locations were observed upon stratification of mortality trends by census region. The Midwest exhibited the highest overall AAMR (0.10), followed by the West (0.09), the Northeast (0.08), and the South (0.07). The AAMR for the Midwest region decreased from 1999 to 2013 (APC: -3.69), before subsequently increasing from 2013 to 2020 (APC: 2.92). The West exhibited a consistent decrease in the AAMR from 1999 to 2020 (APC: -1.59). Variations in the Northeast were observed as the AAMR declined from 1999 to 2004 (APC: -10.41), after which an increment from 2004 to 2020 was noted (APC: 1.66). In the South, the rate of decline varied, with the APC being -6.25 from 1999 to 2006, and then -0.66 from 2006 to 2020. States with the highest overall AAMR included Nevada (0.04), Georgia (0.05), and South Carolina (0.06), whereas those on the other end of the spectrum included Vermont (0.16), Missouri (0.16), and Oregon (0.16).
Conclusion: We observed a decrease in mortality of patients with AIHA from 1999 to 2020. Males, residents of non-metropolitan areas, and the Midwest exhibited the highest overall AAMR. Targeted interventions are needed for these vulnerable populations to curb the rise in mortality of patients with AIHA.