Table 1.

Commonly used diagnostic criteria for HLH, adapted from Henter et al. (8).

A diagnosis is consistent with HLH if 5/8 of the below criteria are met, or if the patient has a molecular diagnosis of genetic HLH (including: PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, SH2D1A, or XIAP/BIRC4)
1. Fever ≥38.5°C
2. Splenomegaly
3. Cytopenias (affecting at least 2 lineages)
Hemoglobin <9 g/dL (in infants <4 weeks: hemoglobin <10 g/dL)
Platelets <100 × 103/mL
Neutrophils <1 × 103/mL
4. Hypertriglyceridemia (fasting, >265 mg/dL) and/or hypofibrinogenemia (<150 mg/dL)
5. Hemophagocytosis in bone marrow, spleen, lymph nodes, liver, or other tissue
6. Low or absent NK cell activity
7. Ferritin >500 ng/mL
8. Elevated sCD25 (soluble IL-2 receptor): >2,400 U/mL or elevated based on the laboratory-defined normal range