Background Aplastic anemia (AA) is a rare, life-threatening hematologic disorder characterized by pancytopenia and a hypocellular bone marrow. The pathophysiology of AA can be divided into subtypes: immune mediated destruction in idiopathic cases, chemical and physical damage from drugs and external agents, or secondary to constitutional genetic defects (Young, 2018). What was once a mysterious disease which was nearly invariably fatal now has an excellent prognosis with the development of immunosuppressive therapy and bone marrow transplantation (Brodsky, 2005). However, nationally representative data on factors affecting length of stay and outcome in patients with AA, particularly of varying subtypes, has not been well described.

Methods The goal of this study was to identify clinical characteristics and risk factors associated with adverse outcomes in patients with AA. The National Inpatient Sample (NIS) database from 2015-2022 was used to identify a cohort of patients with an anytime diagnosis of AA. ICD-9 diagnosis codes of D611 (drug-induced aplastic anemia), D612 (aplastic anemia due to other external agents), D613 (idiopathic aplastic anemia), and D619 (aplastic anemia, unspecified) were used for data collection. Data collected for these patients included demographics, social determinants of health such as income and hospital location, bone marrow biopsy performed, and outcome. Subgroup analyses were also performed with respect to gender, bone marrow biopsy status, etiology of AA, and hospital location. Continuous variables were compared using Mann-Whitney test and categorical variables were compared using Pearson's Chi-Square test. Linear and logistic regression analysis were performed to assess effect estimates for mortality and length of stay.

Results A retrospective cohort of 16102 patients were included in this study, of which 49% were male (mean age 62) and 51% were female (mean age 63). Males had increased mortality (6.75% vs 5.92%, p=0.029) and greater average charges assessed during their hospitalization ($55,322 vs $51,574, p=0.001). Patients undergoing bone marrow biopsy were younger (56 years old vs 63 years old, p<0.001), assessed greater average charges ($114,462 vs $49,296, p<0.001), and had a greater length of stay (9 days vs 5 days, p<0.001). They were less likely to be electively admitted (8.92% vs 14.63%, p<0.001) and more likely to be admitted at an urban teaching facility (87.97% vs 77.18%, p<0.001). Compared to patients with AA due to drugs or external agents, patients with idiopathic AA were younger (24 vs 65, p<0.001), assessed greater average charges ($73,722 vs $47,704, p<0.001), electively admitted at a greater rate (28.16% vs 12.07%, p<0.001), more likely to be admitted at an urban teaching facility (89.51% vs 72.36%, p<0.001), more likely to undergo bone marrow biopsy (11.58% vs 7.10%, p<0.001), and had lower mortality (3.56% vs 7.52%, p<0.001). There were no statistically significant differences in mortality based on hospital location (p=0.307) or patient race (p=0.167). Logistic regression with respect to mortality revealed that age (OR: 1.02, p<0.001) was a predictor of increased mortality, and female gender was associated with decreased mortality (OR: 0.86, p=0.027). Linear regression for length of stay showed a significant increase in length of stay in patients undergoing bone marrow biopsies (coeff 0.76, p<0.001), those electively admitted (coeff 0.41, p<0.001), those with severe illness (coeff 0.27, p<0.001), those at greater risk of mortality (coeff 0.21, p<0.001), and urban locations (coeff 0.13, p<0.001).

Conclusion In this large national database of AA patients, factors associated with an increased risk of mortality included male gender and older patients. Patients with AA due to drugs and external agents had a higher mortality compared to patients with idiopathic AA. Younger patients were more likely to be electively admitted, undergo bone marrow biopsy, and be diagnosed with idiopathic AA. Patients in urban locations with more severe illness and those receiving bone marrow biopsies had an increased length of stay. Prospective, multicenter studies are needed to further evaluate these findings.

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2025
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