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.
Pasireotide, sold under the brand name Signifor, is an orphan drug approved in the United States and the European Union for the treatment of Cushings disease in patients who fail or are ineligible for surgical therapy. It was developed by Novartis. Pasireotide is a somatostatin analog with a 40-fold increased affinity to somatostatin receptor 5 compared to other somatostatin analogs. The most common side effects include hyperglycaemia (high blood sugar levels), diabetes, diarrhoea, abdominal pain (stomach ache), nausea (feeling sick), cholelithiasis (gallstones), injection site reactions, and tiredness.Pasireotide was approved for Cushings disease by the European Medicines Agency (EMA) in April 2012  and by the U.S. Food and Drug Administration (FDA) in December 2012.Pasireotide LAR (the long-acting-release formulation) was approved by the FDA for treatment of acromegaly in December 2014, and had been approved for this indication by the EMA in September 2014. References
External links
"Pasireotide". Drug Information Portal. U.S. National Library of Medicine.