Table 2 HLH-2004 Criteria [13, 15]

Molecular Diagnosis

Pathogenic Biallelic Mutation in Genes Associated with HLH

Clinical and Laboratory Criteria

At Least 5 of the following:

Fever

Splenomegaly

Cytopenias

≥ 2 cell lines:

• Hemoglobin < 90 g/L

• Neutrophils < 1 × 10⁹ cells/L

• Platelets < 100 × 10⁹ cells/L

Hypertriglyceridemia and/or Hyperfibrinogenemia

≥ 3 mmol/L

≤ 1.5 g/L

Hyperferritinemia

≥ 500 µg/L

Hemophagocytosis in bone marrow, spleen or lymph nodes without evidence of malignancy

Reduced or absent Natural Killer cell activity

Elevated soluble CD25 (soluble IL-2 receptor)

≥ 2400 U/mL