Diagnostic criteria for hemophagocytic lymphohistocytosis (HLH)

Source: http://www.bloodref.com/myeloid/hlh-diagnosis

HLH can be diagnosed if either of the following two are met:

  1. A gene mutation consistent with familial HLH is present (these include mutations of PRFUNC13D and STX11), OR
  2. At least five out of the eight following diagnostic criteria for HLH are fulfilled:
    • Fever
    • Splenomegaly
    • Cytopenias (affecting ≥2 of 3 lineages in the peripheral blood): Hemoglobin <90 g/L (in infants <4 weeks: hemoglobin <100 g/L); Platelets <100 x109/L; Neutrophils <1.0  x109/L
    • Hypertriglyceridemia and/or hypofibrinogenemia: Fasting triglycerides ≥3.0 mmol/L (≥265 mg/dl), OR fibrinogen ≤1.5 g/L
    • Hemophagocytosis in bone marrow or spleen or lymph nodes
    • Low or absent NK-cell activity (according to local laboratory reference)
    • Ferritin ≥500 ug/L
    • Soluble CD25 (i.e., soluble IL-2 receptor) ≥2,400 U/ml


  1. If hemophagocytic activity is not evident at presentation, further search for hemophagocytic activity is encouraged. If the bone marrow is not conclusive, biopsies of other organs may be obtained. Serial bone marrow aspirates may also be helpful.
  2. The following findings may provide strong supportive evidence for the diagnosis:
    • spinal fluid pleocytosis (mononuclear cells) and/or elevated CSF protein
    • liver biopsy showing histological picture resembling chronic persistent hepatitis
  3. Other findings consistent with the diagnosis are:
    • cerebromeningeal symptoms
    • lymph node enlargement
    • jaundice
    • edema
    • skin rash
    • hepatic enzyme abnormalities
    • hypoproteinemia
    • hyponatremia
    • raised VLDL
    • lowered HDL

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