Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis

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-2Rα level, and elevated ferritin level (>500 μg/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-2Rα 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 μg/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 μg/L. Ten of the 330 patients were diagnosed with HLH. A ferritin level over 10,000 μg/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 μg/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.