Diagnosis of HLH Clinical and testing criteria Hemophagocytic lymphohistiocytosis can be diagnosed if there is a mutation in a known causative gene or if at least 5 of 8 diagnostic criteria based on HLH-2004 protocol (1) are met: Fever (peak temperature of > 38.5° C for > 7 days) Splenomegaly (spleen palpable > 3 cm below costal margin) Cytopenia involving > 2 cell lines (hemoglobin < 9 g / dL [90 g / L], absolute neutrophil count < 100 / mcL [0.10 × 10 9 / L], platelets < 100, 000 / mcL [100 × 10 9 / L]) Hypertriglyceridemia (fasting triglycerides > 177 mg / dL [2.0 mmol / L] or > 3 standard deviations [SD] more than normal value for age) or hypofibrinogenemia (fibrinogen < 150 mg / dL [1.5 g / L] or > 3 SD less than normal value for age) Hemophagocytosis (in biopsy samples of bone marrow, spleen, or lymph nodes) Low or absent natural killer cell activity Serum ferritin > 500 ng / mL (> 1123.5 pmol / Lng / mL) Elevated soluble interleukin-2 (CD25) levels (> 2400 U / mL or very high for age) Genetic mutations associated with HLH include PRF1 RAB27 STX11 STXBP2 UNC13D XLP Because some of these tests may not be widely available and HLH is uncommon, patients are usually referred to specialized centers for evaluation.