Markers of hemophagocytic lymphohistiocytosis are associated with survival in critically ill patients
European Heart Journal: Acute Cardiovascular Care(2024)
Abstract
Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Association for the Promotion of Research on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) and the Ludwig Boltzmann Cluster for Cardiovascular Research Background/Introduction Patients admitted to the intensive care unit (ICU) often show systemic immune dysregulation paired with significantly increased inflammatory activity. Haemophagocytic lymphohistiocytosis (HLH) represents a rare syndrome characterized by fever, inflammation, cytopenia, and organ dysfunction. Inappropriate survival of cytotoxic T cells as well as histiocytes triggers cytokine storm, accompanied by the occurrence of hemophagocytosis and multi-organ failure. prevalence of HLH in critical illness continues to be a topic of discussion but most certainly remains underreported. This circumstance often leads to delays in the necessary immunosuppressive therapy due to difficulty in early diagnosis. Purpose In the present study, we aimed to illuminate the prospective value of the individual HLH criteria in a cohort of critically ill patients. Although the prevalence of this syndrome might be low, isolated markers of HLH could help to assess the extent of inflammatory activation and further be of use in predicting the outcome of patients admitted to the ICU. Methods This was a prospective, observational cohort study. 176 consecutive patients admitted to a cardiac ICU were included over the course of one year. Available HLH criteria were recorded except for biopsy samples of bone marrow and measurements of low or absent natural killer cell activity. For soluble CD25 (sCD25) a specific ELISA kit was used according to the manufacturer's instructions. Results The median age was 67.51 years (IQR: 57.50-77.41) and 38.64% of the included patients were female. The total 30-day mortality was calculated to be 25.57% and positivity for two or more criteria of HLH was found to be associated with depicted mortality (p = 0.033). Analyzing the individual parameters, only sCD25 was found to be a predictor of death within the first 30 days (p < 0.001). The combination of triglycerides and fibrinogen did not predict outcomes. However, low fibrinogen values were found to possess prognostic merit in regard to mortality (p= 0.019). In multivariate analysis, both sCD25 and fibrinogen remained a significant predictor of 30-day survival after adjustment for age, sex, and BMI (sCD25 p < 0.001, fibrinogen p = 0.042). Finally, the addition of fibrinogen was able to improve the prognostic value of the SAPS II score significantly (ROC curve, SAPS II – AUC: 0.790, SAPS II & fibrinogen – AUC: 0.827, p = 0.045). Conclusion We provided evidence for the prognostic value of certain markers of HLH in critically ill patients. Positivity for two or more criteria was found to be associated with an increased 30-day mortality. Moreover, sCD25 and fibrinogen independently predicted outcomes in multivariate analysis after adjustment for age, sex, and BMI. The addition of fibrinogen was able to improve the prognostic properties of the SAPS II score.Figure 1Figure 2
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