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Pediatr Blood Cancer. 2014 Nov;61(11):2101-3. doi: 10.1002/pbc.25058. Epub 2014 Apr 21.

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

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Pediatric Hematology and Oncology, University Hospital Medical Center, Hamburg, Germany.


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.


HLH; diagnostic criteria; ferritin; hemophagocytic lymphohistiocytosis; hyperinflammation; macrophage activation syndrome

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