List of diagnostic criteria for HLH that were used in the Histiocyte Society HLH-2004 study
| (A) Genetic defect consistent with HLH or (B) 5 out of 8 clinical and laboratory criteria fulfilled |
| Fever |
| Splenomegaly |
| Cytopenia in ≥2 cell lineages |
| Hemoglobin <9 g/dL, in neonates <10 g/dL |
| Platelet count <100 × 103/mL |
| Neutrophil count <1 × 103/mL |
| Hypertriglyceridemia (>265 mg/dL) or hypofibrinogenemia (<150 mg/dL) |
| Hyperferritinemia (>500 ng/mL) |
| Soluble CD25 >2400 U/mL (or elevated compared with laboratory-defined normal ranges) |
| Hemophagocytosis in bone marrow, spleen, lymph nodes, or liver |
| Low or absent NK-cell cytotoxicity |
| (A) Genetic defect consistent with HLH or (B) 5 out of 8 clinical and laboratory criteria fulfilled |
| Fever |
| Splenomegaly |
| Cytopenia in ≥2 cell lineages |
| Hemoglobin <9 g/dL, in neonates <10 g/dL |
| Platelet count <100 × 103/mL |
| Neutrophil count <1 × 103/mL |
| Hypertriglyceridemia (>265 mg/dL) or hypofibrinogenemia (<150 mg/dL) |
| Hyperferritinemia (>500 ng/mL) |
| Soluble CD25 >2400 U/mL (or elevated compared with laboratory-defined normal ranges) |
| Hemophagocytosis in bone marrow, spleen, lymph nodes, or liver |
| Low or absent NK-cell cytotoxicity |
According to the revised diagnostic criteria guideline of the HLH-2004 protocol, HLH is assumed if either a genetic diagnosis consistent with HLH is present (A) or if 5 out of 8 criteria are fulfilled (B). The finding of a genetic defect does not mean that a patient has acute hyperinflammatory HLH, only that they have a predisposition to the syndrome of HLH.10