Abstract
Background:Aplastic anemia (AA) is a rare but serious hematologic disorder that results from immune-mediated destruction of hematopoietic stem cells and leads to bone marrow failure and pancytopenia. Patients often require blood transfusions and face high in-hospital complication and mortality rates. Previous studies have been limited by small cohorts and short follow-up periods. Nationwide trends in AA hospitalizations and independent predictors of in-hospital mortality remain poorly defined. We aimed to determine temporal trends in in-hospital mortality among AA hospitalizations from 2016 to 2022 and to evaluate whether patient factors such as older age, higher comorbidity burden and longer hospital stays were independently associated with higher mortality.
Methods:We conducted a retrospective cohort study to identify hospitalizations for aplastic anemia using ICD-10-CM diagnosis codes in the U.S. National Inpatient Sample (NIS) from 2016 to 2022. Annual hospitalization volumes and crude mortality rates were calculated using discharge weights. Temporal trends were assessed via survey-weighted logistic regression to estimate the adjusted odds of death per calendar year. Survey-weighted linear regression assessed annual changes in mean length of stay (LOS) and total hospital charges. Independent predictors of in-hospital mortality were determined using multivariable survey logistic regression, adjusting for age, Charlson comorbidity index, LOS, ZIP-code income quartile and hospital bed size. Significance was set at p<0.05, with all analysis performed on Stata v18.0.
Results:There were 80,610 AA hospitalizations from 2016 to 2022, with annual hospitalization volumes stable (11,595 in 2016 vs. 11,545 in 2022). Patients had a mean age of 56 years; 51.2% were female and 48.8% were male. The most common comorbidities were hypertension (26%), chronic kidney disease (22%) and cancer (30%). Additionally, the most frequent in-hospital complications in AA patients were electrolyte disturbances (35%), respiratory failure (17%) and sepsis or pneumonia (18%), with 3.3% of patients requiring mechanical ventilation. Crude in-hospital mortality in AA patients rose from 5.7% in 2016 to a peak of 8.3% in 2021 before declining to 6.8% in 2022 (p-trend<0.001). In adjusted temporal analysis, each calendar year was associated with a 4.2% higher odds of death (adjusted odds ratio [aOR] 1.04 per year; 95% CI 1.01–1.08; p=0.018). In multivariable models, older age (aOR 1.04 per year; 95% CI 1.02–1.05; p<0.001), higher Charlson comorbidity index (aOR 1.29 per point; 95% CI 1.22–1.37; p<0.001), and longer LOS (aOR 1.03 per day; 95% CI 1.00–1.06; p=0.049) were independently associated with increased mortality. Moreover, ZIP-code income quartile and hospital bed size were not significant predictors. Mean length of stay increased from 8.4 to 10.4 days over the period (adjusted increase 0.30 days per year; 95% CI 0.17–0.44; p<0.0001), and mean total charges rose from $106,275 to $187,005 (adjusted increase $12,746/year; 95% CI $8,948–$16,544; p<0.0001). In multivariable linear models of resource use, teaching hospital status was the strongest institutional predictor, adding 2.16 days to LOS (95% CI 1.73–2.59; p<0.001) and $54,346 to total charges (95% CI 45,486–63,207; p<0.001).
Conclusion:Our retrospective NIS study shows a significant rise in in-hospital mortality among patients with aplastic anemia, accompanied by progressive increases in length of stay and hospital charges. In our analysis, advanced age, greater comorbidity burden, and prolonged LOS were independently associated with higher in-hospital mortality in AA patients. Findings from our study highlight the need for earlier risk stratification and more aggressive management, such as intensified supportive care and rapid referral to specialized centers, in these high-risk patients. Further research is needed to determine whether targeted interventions based on these predictors can improve outcomes in patients hospitalized with aplastic anemia.
