A Man with Thrombocytopenia

Posted by • January 15th, 2016

1-11-2016 12-00-15 PM

In the latest Case Record of the Massachusetts General Hospital, an 18-year-old man presented with fever, abdominal pain, and thrombocytopenia. Abdominal imaging studies showed nonspecific fluid collection and necrotic lymph nodes, and there were elevated levels of C-reactive protein and ferritin. A diagnostic procedure was performed.

A ferritin level as high as 7000 ng/ml is a marker of macrophage activation and is associated with systemic inflammatory diseases, such as systemic juvenile idiopathic arthritis (Still’s disease), acute or chronic inflammatory disorders, liver or renal failure, hemolytic anemia, hematologic cancers, and a hemophagocytic syndrome.

Clinical Pearl

• What causes hemophagocytic lymphohistiocytosis?

Hemophagocytic lymphohistiocytosis (HLH) is caused by an impairment of the cytolytic activity of T cells and natural killer cells and leads to uncontrolled T-cell activation and increased secretion of cytokines, processes that directly activate macrophages. Proliferation and activation of benign macrophages is associated with phagocytosis of hematopoietic elements throughout the reticuloendothelial system. Activated macrophages also secrete ferritin, leading to hyperferritinemia.

Clinical Pearl

• Is hemophagocytosis sensitive or specific for HLH?

Hemophagocytosis is not sensitive for HLH and is reported in 25 to 100% of patients with HLH. It is also not specific for HLH, because hemophagocytosis can occur after blood transfusion, during the postoperative period, and in patients with systemic inflammation, such as sepsis.

Figure 2. Bone Marrow–Biopsy Specimen.

Morning Report Questons

Q: Describe some of the features of HLH.

A: HLH has familial and acquired forms. Although familial HLH mostly occurs during the first year of life, it may occur later in some affected patients. Acquired HLH in adults is usually triggered by infection, cancer (most commonly lymphoma), or autoimmune disease (in which case it is termed the macrophage activation syndrome). Infection, most commonly with Epstein–Barr virus (EBV), triggers most forms of HLH, even in patients with cancer or with familial HLH.

Q: How is HLH diagnosed?

A: HLH is a clinical diagnosis that is based on eight diagnostic criteria. These criteria were developed for the diagnosis of HLH in children and may be less effective in adults. At least five of the following eight criteria must be present for a diagnosis to be established: fever; splenomegaly; cytopenia; fasting triglyceride levels >3 mmol/liter and/or fibrinogen level <1.5 g/liter; ferritin level >500 ng/ml; soluble CD25 level >2400 U/ml; decreased or absent natural killer cell activity; or hemophagocytosis in bone marrow, central nervous system, or lymph nodes. In children younger than 3 years of age, a serum ferritin level higher than 10,000 ng/ml is about 95% sensitive and specific for HLH.

Comments are closed.