Neutropenia classification
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Daniel A. Gerber, M.D. [2]
Overview
Neutropenia may be classified according to severity based on absolute neutrophil count on blood cell count differential into three subtypes: mild, moderate, and severe.
Classification
Neutropenia may be classified according to severity into three subtypes: mild, moderate, and severe. Neutropenia is calculated based on blood count differential and is defined as an absolute neutrophil count (ANC) less than 1500 cells per µL. Neutropenia is calculated by multiplying the total white blood cell count by the percentage of neutrophils (including both mature neutrophils and band forms). For example, in Caucasian patients, neutropenia severity may be graded as:
- Mild Neutropenia: ANC 1000-1500 cells/µL
- Moderate Neutropenia: ANC 500-1000 cells/µL
- Severe Neutropenia (Agranulocytosis): ANC <500 cells/µL
In other populations, such as African Americans, mild neutropenia may be present without increased risk of complications. Neutropenia in African American individuals is defined as an absolute neutrophil count < 1200 cells/µL.
Neutropenia may be classified according to etiology into two subtypes: congenital (severe, chronic, present at birth) and acquired. Congenital neutropenia may be further classified into the following subtypes:
- Severe congenital neutropenia: A rare inherited form of the disease usually detected soon after birth. It affects children mainly and may result in premature tooth loss and peremptory gum infections. The most severe form of chronic congenital neutropenia is known as Kostmann’s syndrome. It is genetically heterogeneous. Most commonly, it arises as a result of new, autosomal dominant mutations in the gene ELA2, encoding the neutrophil granule protease, neutrophil elastase. Additionally, HAX1, the gene responsible for many cases of autosomal recessively inherited severe congenital neutropenia, may also be affected. The mechanism for congenital neutropenia is not well-understood. There is evidence that mutations in neutrophil elastase, or in other genes associated with syndromic forms of neutropenia, disrupt its intracellular trafficking. Apoptosis may be a final effector for neutropenia.[1]
- Cyclic neutropenia: Generally, cyclic neutropenia tends to occur every 3 weeks and lasts between 3-6 days, due to changing rates of cell production by the bone marrow. It is often present among several members of the same family. Cyclic neutropenia is also the result of autosomal dominantly inherited mutations in ELA2, the gene encoding neutrophil elastase.[2]
- Idiopathic neutropenia: A rare form of neutropenia which develops in children and adults usually in response to an illness. It is diagnosed when the disorder cannot be attributed to any other diseases and often causes life-threatening infections.
- Myelokathexis: A rare form of inherited autosomal dominant disease associated with severe neutropenia. Some, but not all patients present with warts, hypogammaglobulinemia, and recurrent infections. Myelokathexis is also known as the WHIM syndrome. In spite of severe neutropenia in peripheral blood of myelokathexis patients, their bone marrow is hypercellular and is densely packed with mature neutrophils, indicating an impaired mobilization of hematopoietic cells in this disorder. Truncating mutations in the human cytokine receptor CXCR4 gene were identified in most of the families afflicted by myelokathexis. The molecular mechanism is not yet defined. Recent reports demonstrate that CXCR4 mutations appear to result in an increased sensitivity of bone marrow hematopoietic cells to its ligand, a stromal-derived growth factor SDF-1 that provides proliferative and survival signals.[3]
- Autoimmune neutropenia: Most common in infants and young children where the body identifies the neutrophils as foreign bodies and generates antibody to destroy them. This form usually lessens in severity within two years of diagnosis.
- Drug-induced neutropenia: Often concurrently occurring with agranulocytosis, many anti-neoplastic drugs cause neutropenia by bone marrow suppression. Neutropenia and agranulocytosis can also result from antibody or complement-mediated damage to the stem cells. Some drugs may cause increased peripheral destruction of white cells. About 75% of all cases of agranulocytosis in the United States are related to medication. For example, clozapine, procainamide, anti-epileptic, and anti-thyroid drugs (e.g. methimazole, and sulfasalazine) are often implicated.
References
- ↑ Welte K, Zeidler C, Dale DC (2006). "Severe congenital neutropenia". Semin Hematol. 43 (3): 189–95. Text "pmid 16822461" ignored (help)
- ↑ Bellanné-Chantelot C; et al. (2004). "Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register". Blood. 103 (11): 4119–25. PMID 14962902.
- ↑ Aprikyan AA, Liles WC, Park JR, Jonas M, Chi EY, Dale DC. (2000). "Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors". Blood. 95 (1): 320–7. PMID 10607719.