Clinical calculator summary
Original Histiocyte Society HLH-2004 Diagnostic Criteria
Clinical calculator summary
Original Histiocyte Society HLH-2004 Diagnostic Criteria
Two diagnostic pathways: a molecular diagnosis consistent with HLH, or at least five of eight defined clinical and laboratory criteria.
Evidence-based context for fast calculator use
- Purpose:
- Apply the original HLH-2004 diagnostic rule while preserving incomplete assessments.
- Population:
- Primarily patients younger than 18 years in the original protocol; adult application requires caution.
- Factors:
- Molecular diagnosis, Fever, Splenomegaly, Cytopenias, Triglycerides/fibrinogen, Hemophagocytosis, NK activity, Ferritin, Soluble CD25
- Reference:
- Henter et al. Pediatr Blood Cancer. 2007;48:124-131.
HomeHistiocytic DisordersHLH-2004 Diagnostic Criteria Calculator — Hemophagocytic Lymphohistiocytosis
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HLH-2004 Diagnostic Criteria Calculator — Hemophagocytic Lymphohistiocytosis
Clinical Context & Background
This calculator reproduces the original Histiocyte Society HLH-2004 diagnostic criteria. The criteria are fulfilled by either a molecular diagnosis consistent with HLH or at least five of eight clinical and laboratory criteria. Every criterion must be recorded as met, not met, or not assessed; an unassessed criterion is never treated as absent.
The original protocol primarily enrolled patients younger than 18 years and stated that adults would be studied separately. Adult application therefore requires clinical caution. Criteria may emerge sequentially, and a result that does not currently fulfill the rule does not exclude evolving HLH or replace specialist assessment. The calculator is not a treatment trigger.
Formula Logic
HLH-2004 criteria are fulfilled by a molecular diagnosis consistent with HLH OR by at least 5 of 8 clinical and laboratory criteria.Reference Data
| Pathway / finding | Interpretation |
|---|---|
| Molecular diagnosis consistent with HLH | Criteria fulfilled independently |
| At least 5 of 8 criteria met | Criteria fulfilled |
| Fewer than 5 met, but unassessed criteria could reach 5 | Incomplete assessment |
| Fewer than 5 possible after unassessed criteria | Criteria not fulfilled at this assessment |
Clinical Workflow
Use, Interpret, And Continue The Patient Pathway
Expand for workflow guidance, limitations, examples, and related next steps.
Clinical Workflow
Use, Interpret, And Continue The Patient Pathway
Expand for workflow guidance, limitations, examples, and related next steps.
When To Use
- Use when HLH is clinically suspected and the original HLH-2004 diagnostic framework is being applied.
- Record every criterion explicitly as met, not met, or not assessed; use presentation and sequential clinical data as appropriate.
How To Interpret
- A molecular diagnosis consistent with HLH fulfills the criteria independently.
- Without that molecular pathway, at least 5 of 8 criteria must be met.
- Incomplete assessment means outstanding criteria could change whether the 5-of-8 threshold is reached.
What To Do Next
- Integrate the result with urgent specialist assessment, clinical trajectory, molecular testing, and repeat evaluation where criteria may emerge sequentially.
- Do not delay appropriate evaluation or management while waiting for every test.
Limitations
- The original protocol primarily enrolled patients younger than 18 years; adults were to be studied separately.
- Not a stand-alone exclusion test, treatment trigger, or substitute for clinical judgment.
- A result below five criteria at one time does not exclude evolving HLH.
- The original fever criterion did not specify a 38.5 C threshold.
Validated Population
Original HLH-2004 protocol population, primarily patients younger than 18 years with suspected HLH.
Incomplete assessment example
Four criteria met and one criterion not assessed remains incomplete because the outstanding result could reach the five-criterion threshold.
Calculation verification history
Verified
Calculation verification history
Verified: Production browser revalidation
- Three source-backed cases passed through all nine visible production control groups across the molecular-independent, exact five-of-eight, and incomplete-assessment pathways.
- The singular incomplete wording correctly rendered `1 criterion remains unassessed`, resolving the former pluralization defect.
- No unexpected N/A, stale control, literal undefined/null value, or browser-console error was observed.
Case-level evidence is retained in validation/browser-revalidation/hlh-2004-diagnosis-2026-08-03.json.
: Local browser remediation
- Incomplete-assessment wording now uses the grammatically correct singular `1 criterion remains` and plural `criteria remain` forms without changing any HLH-2004 decision rule.
- Ten source-backed cases passed through visible local browser controls across 11 submissions, covering the independent molecular path, exact 5-of-8 threshold, incomplete and not-fulfilled branches, singular/plural wording, required-field validation, and reset/repeat behavior.
- The existing calculator-specific audit passed 512/512. Production status remains open until this commit is deployed and the public route is revalidated.
Local case-level remediation evidence is retained in validation/browser-production/hlh-2004-diagnosis.local-remediation.json.
: Production browser validation
- Ten source-backed cases were exercised on the public production route through visible browser controls; 7/10 case records passed their expected-versus-observed assertions across 11 visible submissions.
- Overall browser status: failed-ui-and-console. low: Incomplete-assessment interpretations use incorrect grammar: `1 criterion remain` for one unknown and `2 criterions remain` or `8 criterions remain` for multiple unknowns. | medium: Production emitted minified React error #418 during route loads/reloads used by this run.
- Case-level inputs, expected and observed results, reset/repeat behavior, failure reproductions, and console evidence are retained in the production-browser evidence record.
Case-level production evidence is retained in validation/browser-production/hlh-2004-diagnosis.json.
: Full validation test
- 512/512 exhaustive decision, molecular-pathway, incomplete-assessment, invalid-input, UI, trace, source-definition, wording, and immutability checks passed.
- No registered master panel calculates HLH-2004; no panel receives inherited verification.
: Calculation and input-contract correction
- Added the independent molecular pathway and required explicit status for all eight criteria; missing, extra, legacy numeric, coercive, null, and unknown values are rejected, and Not assessed is never treated as Not met.
- Removed the unsupported suspicious category, restored exact source definitions and incomplete-assessment logic, and added pediatric-origin, adult-caution, sequential-criteria, non-exclusion, and non-treatment-trigger wording.
Verification confirms the calculator implementation against the cited model; it is not independent clinical validation, regulatory approval, or medical advice.
Related Tools
Frequently Asked Questions
Can a molecular diagnosis fulfill HLH-2004 without five clinical criteria?
Yes. A molecular diagnosis consistent with HLH is an independent pathway in the original criteria.
Does Not assessed mean the criterion is absent?
No. Unassessed criteria remain unknown. If they could change whether five criteria are reached, the calculator returns Incomplete assessment.
Does failing to meet five criteria exclude HLH?
No. Criteria can emerge sequentially, and the framework is not a stand-alone exclusion test.
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