Proposed laboratory diagnostic algorithm based on degranulation assays for patients presenting with HLH. Normal values have to be determined in the diagnostic laboratory for the evaluation of resting NK-cell degranulation. For the centers participating in this study, resting NK-cell degranulation was considered defective if < 5%, abnormal if 5%-10%, and normal if > 10%, cutoffs that have proven to be useful. Analyses of activated NK-cell degranulation is recommended for all patients. AICD indicates activation-induced cell death.