Evaluating the optimal serum ferritin level to identify hemophagocytic lymphohistiocytosis in the critical care setting

Ferritin is known to be involved in numerous physiological roles, such as iron storage, as well as various pathological conditions and in generalized inflammatory states. Hyperferritinemia is also encountered in the setting of hemophagocytic lymphohistiocytosis (HLH). Current diagnostic criteria exist to define HLH based on several clinical and biochemical markers, including the serum ferritin level. In this study, we retrospectively evaluated the value of ferritin >500 ng/mL in diagnosing HLH in 344 consecutive patients admitted to the medical intensive care unit at our hospital. Nine cases of HLH were identified. Comparison of the HLH with the non-HLH group showed that their maximum median serum ferritin level was 25,652 (range 1977–100,727 ng/mL) versus 1180 (503–85,168 ng/mL) (P < 0.001), platelets were 30 (5–92 × 10³/μL) versus 113 (0–507 × 10³/μL) (P < 0.001), absolute neutrophil counts were 2.56 (0.02–23.7 × 10³/μL) versus 7.7 (0.01–82.7 × 10³/μL) (P = 0.002), and triglycerides were 255 (156–394 mg/dL) versus 127 (17–624 mg/dL) (P = 0.002), respectively. Using a receiver operating characteristic curve, the optimal maximum serum ferritin level for the diagnosis of HLH was 3951 ng/mL, exceeding the current diagnostic cutoff set forth in the HLH-2004 guidelines. These data suggest that a higher cutoff value of ferritin level may have improved utility in the diagnosis of secondary HLH in the critical care setting.