Thrombotic microangiopathy among hospitalized patients: Demographic characteristics, diagnostic trends, and resource use from a national database study

Abstract

Abstract Introduction Thrombotic microangiopathy (TMA) is an uncommon but serious class of microvascular disorders with the ability to lead to microangiopathic hemolytic anemia, thrombocytopenia, and injury to multiple organs. The primary etiologies are hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), while secondary TMAs occur due to malignancy, autoimmune disorder, transplantation, infections, certain drugs, and pregnancy. TMA is underdiagnosed among hospitalized populations and associated with high illness burden and heavy resource use. Large database analyses reflecting demographic profiles and diagnostic patterns remain scarce, especially in the United States, where large-scale discharge data became widely available recently. Methods We conducted a retrospective study using the National Inpatient Sample (NIS), providing a large representative sample of hospital discharges from across the country. Analysis included discharges from 2016 to 2022. TMAs were identified via ICD-10 codes billed as primary or secondary diagnoses. Studied variables included age, sex, primary payer, ZIP code income quartile, hospital bed size and region, admission weekday versus weekend, elective versus non-elective admission, month and year, length of stay (LOS), and All Patient Refined Diagnosis Related Groups (APR-DRG) severity and mortality classifications. Statistical methods included two-sample t test, Wilcoxon rank-sum test, chi-square test, logistic regression, and linear regression. Results Among 13,114 hospitalizations meeting TMA criteria, median age was 51 years (interquartile range [IQR] 35–65) for primary diagnosis and 32 years (IQR 9–56) for secondary diagnosis groups. Females comprised 59% of patients in both groups. Median total charges were $103,171 (IQR $44,384–$235,315) for primary and $75,962 (IQR $30,486–$189,856) for secondary diagnoses. Non-elective admissions accounted for 90% of primary and 91% of secondary encounters. Weekend admissions accounted for 22% and 23%, respectively. Income quartile and insurance status were strongly associated with whether TMA was coded as the primary diagnosis (p < 0.001). Lower-income patients more often had TMA as a primary diagnosis, while higher-income patients were more frequently coded secondarily. Regional variation was noted, with most cases in the Midwest and South. Median LOS was 10 days (IQR 5–21) for primary and 8 days (IQR 4–16) for secondary diagnoses. In our cohort, 80% of patients with a primary diagnosis and 64% with secondary diagnosis were assigned APR-DRG mortality risk levels 3 or 4, indicating major or extreme risk of in-hospital death. Discussion Our data confirm trends from smaller series, including female predominance, wide age distribution, and significant socioeconomic and geographical variation. The predominance of non-elective admissions emphasizes the acute and severe nature of TMA. Length of stay substantially exceeds that of typical hospitalizations, consistent with prior reports. Frequent assignment to high mortality risk groups highlights the serious illness severity and need for timely recognition and intensive support. Socioeconomic and insurance factors are strongly associated with whether TMA is coded as primary diagnosis, suggesting disparities in severity, access to care, or diagnostic coding. Addressing these differences is crucial to improve recognition, management, and outcomes. Conclusion This national dataset shows TMA is correlated with acute presentation, intensive resource use, prolonged hospitalization, elevated mortality risk, and increased hospital cost. Population trends and prolonged stays are consistent with earlier reports. Efforts are needed to support earlier recognition and intervention to reduce the burden of this challenging disorder.