HLH-2004 Diagnostic Criteria (Hemophagocytic Lymphohistiocytosis)
The HLH-2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (Henter and colleagues 2007, Table I).
Open the calculator → Runs in your browser. Data leaves only if you deliberately send a problem report from the interactive tool.
Example
- A molecular diagnosis consistent with HLH
- No
- Fever
- Yes
- Splenomegaly
- Yes
- Hemophagocytosis in bone marrow, spleen or lymph nodes
- Yes
- Infant under 4 weeks old
- No
- Hemoglobin
- 8 g/dL
- Platelets
- 50 x10^9/L
- Neutrophils
- 2 x10^9/L
- Fasting triglycerides
- 300 mg/dL
- Fibrinogen
- 200 mg/dL
The other 5 values
- NK-cell activity LOW OR ABSENT by local laboratory reference
- Pending / not done
- Ferritin
- 900 ug/L
- Whether the soluble CD25 assay has returned
- Resulted
- Soluble CD25
- 5000 U/mL
- No evidence of malignancy
- Yes
Result: 7
The tool opens with these values already filled in. Replace them with your own.
What the result means
- Two paths
- EITHER a molecular diagnosis consistent with HLH, OR 5 of 8 criteria. The molecular path establishes the diagnosis with ZERO criteria.
- Ninth bullet
- "No evidence of malignancy" is printed in the table but is NOT one of the eight. Counting it gives nine.
- Fever
- The primary gives NO temperature threshold. The 38.5 degrees C figure in secondary tables is not in the source.
- Cytopenias
- ONE criterion requiring 2 of 3 lineages: Hb under 9 g/dL (under 10 in infants under 4 weeks), platelets under 100, neutrophils under 1.0 x10^9/L.
- Lipids
- ONE criterion, an OR: triglycerides 265 mg/dL or above, and/or fibrinogen 150 mg/dL or below.
- Ferritin
- 500 micrograms/L or above; micrograms/L and ng/mL are numerically identical.
- sCD25
- 2400 U/mL or above. A send-out assay.
- NK activity
- Low or absent BY LOCAL LABORATORY REFERENCE. No universal cutoff.
- Pending
- PENDING IS NOT NOT-MET. 4 met plus 2 pending does NOT exclude HLH. Untreated HLH is rapidly fatal.
- Scope
- Criteria from a treatment protocol. Not an instruction to start etoposide. Does not identify the trigger. Not the HScore.
What you enter
- A molecular diagnosis consistent with HLH.
- Fever.
- Splenomegaly.
- Hemophagocytosis in bone marrow, spleen or lymph nodes.
- Infant under 4 weeks old, which raises the hemoglobin threshold from 9 to 10 g/dL.
- Hemoglobin.
- Platelets.
- Neutrophils.
- Fasting triglycerides.
- Fibrinogen.
The other 5 fields
- A molecular diagnosis consistent with HLH. THIS IS AN ALTERNATIVE PATH: yes establishes the diagnosis on its own, with none of the eight criteria.
- Fever. The primary table gives NO temperature threshold; the 38.5 degrees C figure in secondary tables is not in the source.
- Splenomegaly. No size threshold is given in the source.
- Hemophagocytosis in bone marrow, spleen or lymph nodes. Its absence at presentation does not exclude HLH; the source encourages a further search.
- Hemoglobin. Counts as a low lineage under 9 g/dL (source 90 g/L), or under 10 in infants under 4 weeks.
- Platelets. Counts as a low lineage under 100 x10^9/L.
- Neutrophils. Counts as a low lineage under 1 x10^9/L. 2 of the 3 lineages must be low for the single cytopenia criterion.
- Fasting triglycerides. Meets at 265 mg/dL or above (source 3.0 mmol/L). Shares ONE criterion with fibrinogen: either alone satisfies it.
- Fibrinogen. Meets at 150 mg/dL or BELOW (source 1.5 g/L). Shares one criterion with triglycerides.
- NK-cell activity LOW OR ABSENT by local laboratory reference. There is no universal cutoff, so the local laboratory verdict is the input. A send-out assay: use "pending" if it has not returned.
- Ferritin. Meets at 500 micrograms/L or above; micrograms/L and ng/mL are numerically identical.
- Whether the soluble CD25 assay has returned. "pending" makes the criterion UNEVALUABLE and the number is ignored - pending is not the same as not met.
- Soluble CD25 (soluble IL-2 receptor). Meets at 2400 U/mL or above. A send-out assay: use "pending" if it has not returned.
- No evidence of malignancy. REPORTED BUT NOT COUNTED - it is printed in the primary table but is not one of the eight criteria.
How this is calculated
Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131, Table I. Read the source ↗
A reference and educational tool. Not medical, legal, or financial advice, and not a substitute for clinician judgment.