Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis

Pediatr Blood Cancer. 2008 Jun;50(6):1227-35. doi: 10.1002/pbc.21423.

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially lethal condition characterized by a pathologic inflammation. The diagnostic criteria for HLH include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, abnormal natural killer cell (NK cell) functional assay, elevated soluble IL-2Ralpha level, and elevated ferritin level (>500 microg/L). Institution of timely therapy in these critically ill patients may be delayed by difficulties establishing the diagnosis. NK cell functional assay and soluble IL-2Ralpha level may require send-out to a specialized lab. However, ferritin level is available on a same-day basis at most institutions. In this study, we examined the utility of quantitative ferritin levels in diagnosing HLH.

Procedure: All patients with ferritin values >500 microg/L obtained at Texas Children's Hospital between January 10, 2003 and January 10, 2005 were identified. Patient charts were reviewed for ferritin levels and hospital course.

Results: During the study interval, 330 patients had ferritin levels >500 microg/L. Ten of the 330 patients were diagnosed with HLH. A ferritin level over 10,000 microg/L was 90% sensitive and 96% specific for HLH. Another diagnostic category with significantly elevated ferritin level was illness of unknown cause (n = 10), and only two of these patients were fully evaluated for HLH.

Conclusions: Ferritin levels above 10,000 microg/L appear to be specific and sensitive for HLH. In patients without a significant medical history and a new onset of febrile illness with highly elevated ferritin levels, the diagnosis of HLH should be evaluated.

MeSH terms

  • Biomarkers / blood
  • Child
  • Female
  • Ferritins / blood*
  • Humans
  • Lymphohistiocytosis, Hemophagocytic / blood
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Male
  • Predictive Value of Tests
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • Ferritins