Activated macrophages secrete ferritin and plasminogen activator leading to hyperfibrinolysis. Diagnosis
The blood count typically shows decreased numbers of blood cells—including a decreased number of circulating red blood cells, white blood cells, and platelets. The bone marrow may show hemophagocytosis. The liver function tests are usually elevated. A low level of the protein albumin in the blood is common.The serum C reactive protein, erythrocyte sedimentation rate, and ferritin level are markedly elevated. In children, a ferritin above 10000 is very sensitive and specific for the diagnosis of HLH, however, the diagnostic utility for ferritin is less for adult HLH patients.The serum fibrinogen level is usually low and the D-dimer level is elevated. The sphingomyelinase is elevated.Bone marrow biopsy shows histiocytosis. Classification
Primary HLH, also known as familial haemophagocytic lymphohistiocytosis (FHL) or familial erythrophagocytic lymphohistiocytosis, is a heterogeneous autosomal recessive disorder found to be more prevalent with parental consanguinity.Secondary haemophagocytic lymphohistiocytosis (acquired haemophagocytic lymphohistiocytosis) occurs after strong immunologic activation, such as that which can occur with systemic infection, immunodeficiency, or underlying malignancy.Both forms are characterized by the overwhelming activation of normal T lymphocytes and macrophages, invariably leading to clinical and haematologic alterations and death in the absence of treatment.A subtype of primary HLH where the inflammation is limited to the central nervous system has been described. Diagnostic criteria
The current (2008) diagnostic criteria for HLH are1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11. OR
2.
Fulfillment of five out of the eight criteria below:

Fever (defined as a temperature >100.3 °F, >38 °C)
Enlargement of the spleen
Decreased blood cell counts affecting at least two of three lineages in the peripheral blood:
Haemoglobin <9 g/100 ml (in infants <4 weeks: haemoglobin <10 g/100 ml) (anemia)
Platelets <100×109/L (thrombocytopenia)
Neutrophils <1×109/L (neutropenia)
High blood levels of triglycerides (fasting, greater than or equal to 265 mg/100 ml) and/or decreased amounts of fibrinogen in the blood (≤ 150 mg/100 ml)
Ferritin ≥ 500 ng/ml
Haemophagocytosis in the bone marrow, spleen or lymph nodes
Low or absent natural killer cell activity
Soluble CD25 (soluble IL-2 receptor) >2400 U/ml (or per local reference laboratory)In addition, in the case of familial HLH, no evidence of malignancy should be apparent. 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 pediatric populations and have not been validated for adult HLH patients. Attempts to improve diagnosis of HLH have included use of the HScore, which can be used to estimate an individuals risk of HLH. In adults, soluble IL-2 receptor has been found to be a very sensitive marker for HLH, demonstrating 100% sensitivity for ruling out HLH below a cutoff of 2400 U/mL and optimal cutoff for ruling in at 2515 U/mL (sensitivity, 100%; specificity, 72.5%), with 93% specificity at >10 000 U/mL.