Table 3.

HLH-2004 diagnostic criteria

The diagnosis of HLH can be established if any one of two given factors is fulfilled:

1. A molecular diagnosis consistent with HLH

2. Diagnostic criteria for HLH are fulfilled (5 or more of 8 criteria below)*

Fever

Splenomegaly

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

Hemoglobin <90 g/L (in infants <4 weeks old; hemoglobin <100 g/L)

Platelets <100 × 109/L

Neutrophils <1.0 × 109/L

Hypertriglyceridemia and/or hypofibrinogenemia: fasting

Hypertriglyceridemia ≥3.0 mmol/L (i.e., ≥265 mg/dl), fibrinogen ≤1.5 g/L

Hemophagocytosis in the bone marrow, spleen, or lymph nodes

Low or absent natural killer cell activity (according to the local laboratory reference)

Ferritin ≥500 µg/L

Soluble CD25 (i.e., sIL2r) ≥2400 U/mL

* Supportive criteria include neurological symptoms, cerebrospinal fluid pleocytosis, conjugated hyperbilirubinemia and transaminitis, hypoalbuminemia, hyponatremia, elevated D-dimers, and lactate dehydrogenase. The absence of hemophagocytosis in the bone marrow does not exclude the diagnosis of HLH.