#incomplete - Life-threatening severe hyper-inflammation ; type of cytokine storm - presents similar to sepsis - ↑ ferritin, transaminases (ALT and AST), and hepatosplenomegaly are usually seen - ↓ fibrinogen and [[DIC]] can present as diffuse bleeding # Diagnostic Criteria for HLH A molecular diagnosis consistent with HLH (eg pathologic mutations of PRF1, UNC13D, or STX11) OR 5/8 criteria below: - Fever > 38 °C - [[splenomegaly]] - Decreased blood cell counts affecting at least two of three lineages in the peripheral blood: - Haemoglobin <90 (in infants <4 weeks →Hb < 100) - [[thrombocytopaenia]] (platelets < 100) - neutropenia (<1) - hyperlipidaemia +/- fibrinogen ≤ 150mg/100mL - ferritin ≥ 500 ng/mL - Haemophagocytosis in bone marrow, spleen, or lymph nodes - **Note:** Despite the disorder's name, hemophagocytosis is *not* required to be present for the diagnosis. It may not be present in early stages of the disordered inflammation - Low or absent natural killer cell activity - Soluble CD25 (soluble IL-2 receptor) elevated > Not all five out of eight criteria are required for diagnosis of HLH in adults, and a high index of suspicion is required for diagnosis, as delay results in increased mortality. The diagnostic criteria were developed in paediatric populations and have not been validated for adult HLH patients