Outcomes of plasmapheresis in patients with HLH: A nationwide analysis from 2016–2022

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome characterized by uncontrolled immune activation and cytokine storm. Despite high morbidity and mortality, standardized treatment remains challenging, particularly in adult populations. Plasmapheresis (PLEX) has been utilized in HLH management to remove inflammatory mediators, but evidence supporting its efficacy remains sparse and largely limited to case reports and small case series. To date, no large-scale analysis has evaluated inpatient outcomes associated with PLEX in HLH. Methods: Using the National Inpatient Sample (NIS) from 2016 to 2022, we identified adult hospitalizations with a diagnosis of HLH using ICD-10 codes. Patients undergoing PLEX were identified using procedural codes. Discharge weights provided by the NIS were applied to generate nationally representative estimates. We compared demographics, clinical characteristics, and outcomes between those who did and did not receive PLEX. Multivariable logistic and linear regression analyses were used to adjust for potential confounders, including age, sex, race, insurance status, hospital location and size, Charlson Comorbidity Index, length of stay, use of mechanical ventilation, presence of shock, and admission to a critical care unit. Results: A total of 25,240 hospitalizations with HLH were identified, of whom 315 (1.2%) underwent PLEX. Patients receiving PLEX were younger (mean age 45.2 vs. 51.4 years, p=0.005), with no significant differences by race or comorbidity index. PLEX was more frequently performed in urban teaching hospitals (87%, p=0.2). Unadjusted in-hospital mortality was higher in the PLEX group (31% vs. 18%, p=0.02); however, after adjusting for age, sex, race, hospital characteristics, insurance, Charlson comorbidity index, length of stay, use of mechanical ventilation, and presence of shock, PLEX was not significantly associated with mortality (adjusted risk difference: −6.18%, p=0.80). PLEX was associated with a significantly longer length of stay (+8.2 days, p=0.038) and higher mean hospitalization costs ($677,073.70 vs. $235,721.50; adjusted cost increase: +$323,513.80, p=0.042). Conclusion: In this large national cohort, PLEX was infrequently used in HLH hospitalizations and was not associated with improved inpatient mortality after adjustment for severity markers including mechanical ventilation and shock. However, it was linked to prolonged hospitalization and increased healthcare costs. These findings highlights the need for prospective studies to better define the role of PLEX in HLH management.