Determining the Optimal Cut-Off Threshold for Ferritin in the Diagnosis of Hemophagocytic Lymphohistiocytosis in Pediatric Intensive Care
CCCF ePoster library. Ayoubzadeh S. Nov 8, 2018; 233440; 86 Disclosure(s): Research Grant - Student Research Opportunities Program, Schulich School of Medicine and Dentistry
Ms. Sasha Ayoubzadeh
Ms. Sasha Ayoubzadeh
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Introduction/Background: Hemophagocytic lymphohistiocytosis (HLH) is a devastating condition characterized by severe immune dysregulation Current diagnostic criteria define HLH based on several clinical and biochemical markers, including hyperferritinemia (ferritin level >500 µg/L). The promptness and availability of serum ferritin make it an important screening tool for HLH, as the extent to which ferritin is elevated in HLH is atypical of other conditions. However, this may not extend to critically ill patients who often have extensive inflammation resulting in hyperferritinemia. The current ferritin cutoff of 500 µg/L may confound the evaluation of HLH in critically ill patients and result in unnecessary, costly and invasive investigations to rule out HLH in these patients. Therefore, it is important to determine a more specific ferritin threshold in critically ill pediatric patients.  


Objectives: The purpose of this study was to compare the ferritin levels of patients with and without HLH admitted to the pediatric intensive care unit (PICU). We also compared other HLH-diagnostic criteria between the two groups.

Methods: A retrospective chart review was performed on all PICU admissions with a ferritin level >500 µg/L from 2010-2018. Demographic data and data on all diagnostic criteria for HLH were collected. All analyses were conducted using SPSS v25 (IBM Corp., Armonk, NY, USA). For continuous variables, Mann-Whitney U tests were used; for categorical variables, Exact chi-square tests were used.

Results: A total of 65 patient admissions had a ferritin >500 µg/L in the PICU during the study period. Of these, 17 were determined to have HLH. Mean initial ferritin was 29149.67mg/L for admissions with HLH and 7187.38 m/L for admissions without HLH (p<0.001). Mean maximum ferritin was 45115.65 mg/L for admissions with HLH and 7395.14 mg/L for admission without HLH (p<0.001). Of the diagnostic criteria assessed, splenomegaly (p<0.001), hypertriglyceridemia (p = 0.002), hypofibrinogenemia (p=0.002), cytopenias (p=0.003), and hemophagocytosis in bone marrow, liver, spleen or lymph nodes (p<0.001), were all significantly more common in PICU admissions with HLH than those without.

Conclusion: We found that patients admitted to the PICU with HLH had significantly higher initial and peak ferritin levels compared to other critically ill patients with hyperferritinemia. However, critically ill patients without HLH had a mean ferritin that was 14 times higher than the cutoff threshold of 500 µg/L. This finding supports the need to determine a specific ferritin cutoff suggestive of HLH in critically ill patients. Further analysis is required to determine the appropriate cutoff threshold.  


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