Evans Syndrome in Adults: Demographics, Associations, and Outcomes in a Nationwide Inpatient Sample Study

Background:

Evans syndrome (ES) is a rare disease characterized by the co-occurrence of immune thrombocytopenia and autoimmune hemolytic anemia. ES can occur on its own as a primary (idiopathic) disorder or may be associated with other conditions such as chronic infections, primary immunodeficiencies, systemic autoimmune diseases, and hematological malignancies. Current information on demographics, comorbidities, and outcomes of adult patients with ES remains limited. To address this knowledge gap, we performed a nationwide retrospective study using the National Inpatient Sample database for the years 2016-2021.

Methods:

Admissions of adult patients with ES were identified by the International Classification of Disease, 10^th edition (ICD-10) codes. We defined primary and secondary ES based on the presence or absence of other associated conditions (infectious, autoimmune, primary immunodeficiencies, and hematological malignancies). Prevalence estimates were adjusted using NIS discharge-level weights to represent national data. The categorical variables were compared using Fischer's exact test, and the continuous variables, using linear regression. Multivariate logistic regression was used to identify factors independently associated with in-hospital mortality. All statistical analyses were performed in STATA/BE 18.5.

Results:

We identified 1941 admissions of patients with ES, which was equivalent to an estimated 9705 nationwide admissions from 2016 to 2021. The mean age of patients was 50.8, and 51.8% were women. White patients comprised the largest racial group affected (56.6%), followed by African American (16.5%), and Hispanic (15.6%). Secondary causes of ES were present in 35.1% of admitted patients. Systemic autoimmune diseases defined secondary ES in 50.2% of cases, followed by hematological malignancies in 33.8%, immunodeficiency syndromes in 19.0%, and chronic infections (HIV, chronic hepatitis) in 4.5%. Those with secondary ES were characterized by lower age (47.3 vs. 51.3, p <0.001), increased mean Charlson comorbidity index (2.85 vs.1.96, p <0.001), and increased average duration of hospital stay (8.7 vs. 7.4 days, p<0.001). Commonly observed complications in the ES cohort included bacterial infections (22.4%), thrombotic complications (12.8%), and bleeding (10.7%). Infectious complications were more common in secondary than primary ES (25.1% vs. 20.9%, p=0.03). Overall inpatient mortality in the ES cohort was 5.6%, and it was similar between secondary and primary ES (5.0% vs 5.9%, p=0.39). In multivariate logistic regression analysis, mean Charlson comorbidity index (OR 1.14, p=0.015), thrombotic complications (OR 2.95, p<0.001), and infections (OR 7.78, p<0.001) were significantly associated with inpatient mortality.

Discussion and Conclusions:

To the best of our knowledge, this study represents the largest retrospective analysis of ES to date and the first analysis of ES hospital admissions in the United States. Therefore, our work provides clinically relevant data on demographics, common associations, major complications, and hospitalization outcomes in primary and secondary ES.

We found that systemic autoimmune diseases (primarily systemic lupus erythematosus) and hematological malignancies were the most prevailing underlying cause of secondary ES. These observations correspond to previously published smaller cohort studies conducted in European countries. Although the inpatient mortality was similar between primary and secondary ES admissions, the latter group was found to have an increased length of inpatient stay, which may reflect a more complicated hospital course due to associated conditions and comorbidities. Furthermore, we found that infectious and thrombotic complications occurred in a substantial number of patients with ES and were independent predictors of inpatient mortality. These results should prompt intense clinical vigilance for all patients with ES who are at risk of these major complications.

We acknowledge certain limitations of this study that are inherent to the administrative character of the analyzed database. Thus, future prospective studies are needed to better define epidemiology, disease course, prognosis, and optimal treatment in patients with ES.