Determination of an appropriate cut-off value for ferritin in the diagnosis of hemophagocytic lymphohistiocytosis


  • Contributions: K.L. designed the study, collected patient data, and performed statistical analyses. G.E.J. and K.L.M. collected patient data. C.E.A. designed the study and collected patient data.
  • Conflict of interest: Nothing to declare.


Hyperferritinemia is a hallmark of hemophagocytic lymphohistiocytosis (HLH). In the HLH-2004 criteria, a ferritin value >500 µg/L is considered positive. However, this level was not determined based on evidence. We compared 123 patients with HLH and 320 patients with other hyperferritinemic conditions, calculated a receiver-operating characteristic, and determined sensitivity and specificity for different values. At 2,000 µg/L a trade-off is reached with sensitivity at 70% and specificity at 68%. If familial HLH and virus-associated acquired HLH are analyzed separately, sensitivity and specificity are similar for this level. The results may guide a potential modification of the current HLH criteria. Pediatr Blood Cancer 2014;61:2101–2103. © 2014 Wiley Periodicals, Inc.