The HLH-2004 diagnostic criteria

Criteria for when to suspect HLH

Fulfillment of 5 out of 8 of the following criteria with no evidence of malignancy is suggestive of HLH¹:

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Persistent fever

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Low or absent NK-cell activity

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High sCD25 ≥2400 U/mL

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Splenomegaly

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High ferritin ≥500 µg/L

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Hemophagocytosis*

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Cytopenia
(affecting ≥2 of 3 lineages in the peripheral blood)

• Hemoglobin <90 g/L (in infants <4 weeks: hemoglobin <100 g/L)
• Platelets <100 x 10⁹/L
• Neutrophils <1.0 x 10⁹/L

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Hypertriglyceridemia and/or hypofibrinogenemia

• Fasting triglycerides ≥3.0 mmol/L (ie, ≥265 mg/dL)
• Fibrinogen ≤1.5 g/L

 

NK=natural killer; sCD25=soluble interleukin-2 receptor.
*Hemophagocytosis is not specific nor always present in early stages of the disease.²

How were these criteria developed?

The HLH-2004 criteria were originally developed as inclusion criteria for a clinical study about HLH. Because the presentation of HLH can vary widely from patient to patient, there are some limitations with this criteria.³ For more information on other testing that can be conducted to help confirm or rule out an HLH diagnosis, visit the genetic testing and flow cytometry and ancillary testing pages.

It is also important to rule out any underlying cause such as malignancy, especially lymphoma, or viral infection.³