Markers of Hemophagocytic Lymphohistiocytosis Are Associated with Mortality in Critically Ill Patients

<b>Background:</b> Critically ill patients often display systemic immune dysregulation and increased inflammatory activity. Hemophagocytic lymphohistiocytosis (HLH) represents a rare syndrome defined by the inappropriate survival of cytotoxic T cells and the occurrence of cytokine storms. Although HLH is characterized by relatively high mortality rates, little is known about the predictive value of its diagnostic criteria. Accordingly, our objective was to evaluate these properties within an unselected cohort of critically ill patients admitted to a tertiary intensive care unit (ICU). <b>Methods:</b> This single-center prospective observational study included 176 consecutive patients. Available HLH criteria at admission were assessed, including sCD25 measurements performed using ELISA. <b>Results:</b> Overall, 30-day mortality rates were significantly higher in patients exhibiting two or more criteria of HLH (21.9% vs. 43.3%, <i>p</i> = 0.033). Moreover, sCD25 emerged as an independent risk predictor of 30-day mortality independent of age, sex, the use of vasopressors, and mechanical ventilation (HR 2.72 for the highest tertile vs. lowest tertile, <i>p</i> = 0.012). Additionally, fibrinogen was significantly decreased in non-survivors (<i>p</i> = 0.019), and its addition to the SAPS II score significantly increased its prognostic capability (<i>p</i> = 0.045). In contrast, ferritin and triglyceride levels were not different in survivors versus non-survivors. <b>Conclusions:</b> Critically ill patients displaying two or more HLH criteria exhibit a dramatic increase in 30-day mortality, even in the absence of an established HLH diagnosis. Furthermore, elevated levels of sCD25 and decreased levels of fibrinogen were found to be significant predictors of mortality.