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| '''Editor-in-Chief:''' Aric Hall, M.D. Beth Israel Deaconess Medical Center, Boston, MA[mailto:achall@bidmc.harvard.edu]; [[C. Michael Gibson]], M.S., M.D. | | '''Editor-in-Chief:''' Aric Hall, M.D. Beth Israel Deaconess Medical Center, Boston, MA[mailto:achall@bidmc.harvard.edu]; [[C. Michael Gibson]], M.S., M.D. |
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| ==Overview==
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| '''Neutropenia''' (or '''neutropaenia''', adjective '''neutrop(a)enic''') is a [[Hematology|hematological]] disorder characterized by an abnormally low number of [[neutrophil granulocyte]]s (a type of [[white blood cell]]). Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against [[infection]]s by destroying [[bacterium|bacteria]] in the [[blood]]. Hence, patients with neutropenia are more susceptible to bacterial infections and without prompt medical attention, the condition may become life-threatening. Neutropenia can be [[Acute (medical)|acute]] or [[chronic (medicine)|chronic]] depending on the duration of the illness. A patient has chronic neutropenia if the condition lasts for greater than 3 months. It is sometimes used interchangeably with the term [[leukopenia]]. However, neutropenia is more properly considered a subset of leukopenia as a whole.
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| ==Classification==
| | {{SK}} Neutropaenia |
| There are 3 general guidelines used to classify the severity of neutropenia based on the absolute neutrophil count (ANC) measured in cells per [[microliter]] of blood:
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| * Mild neutropenia (1000 < ANC < 1500) — minimal risk of infection
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| * Moderate neutropenia (500 < ANC < 1000) — moderate risk of infection
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| * Severe neutropenia (ANC < 500) — severe risk of infection.
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| NOTE: These are ranges for Caucasians. Neutropenia in black individuals is defined as ANC < 1200. This is a not well known fact that results in overdiagnosis of neutropenia in black population.<ref name="pmid17404350">{{cite journal |author=Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP |title=Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences |journal=Ann. Intern. Med. |volume=146 |issue=7 |pages=486-92 |year=2007 |pmid=17404350 |doi= |url=http://www.annals.org/cgi/content/abstract/146/7/486}}</ref>
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| ==Types== | | ==[[Neutropenia overview|Overview]]== |
| Severe chronic neutropenia may be present at birth (congenital neutropenia) or may occur at any stage in life (acquired neutropenia).
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| There are several types of severe chronic neutropenia:
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| '''Severe [[congenital]] neutropenia''' — a rare inherited form of the disease usually detected soon after birth. It affects children mainly and may result in premature loss of teeth and peremptory gum infections. The most severe form of chronic congenital neutropenia is known as [[Kostmann syndrome|Kostmann’s syndrome]]. It is genetically heterogeneous. Most commonly, it arises as a result of new, [[autosomal]] [[dominant gene|dominant]] mutations in the gene, ELA2, encoding the neutrophil granule [[protease]], [[neutrophil elastase]], NE. The gene responsible for many cases of autosomal recessively inherited severe congenital neutropenia is HAX1. 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, but the original studies from Dale and Aprikian supporting this pathway were retracted.
| | ==[[Neutropenia historical perspective|Historical Perspective]]== |
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| '''Cyclic neutropenia''' — tends to occur every three weeks and lasting three to six days at a time 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.
| | ==[[Neutropenia classification|Classification]]== |
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| '''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.
| | ==[[Neutropenia pathophysiology|Pathophysiology]]== |
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| '''Myelokathexis''' — a rare form of inherited autosomal dominant disease associated with severe neutropenia. Some but not all patients have Warts, [[Hypogammaglobulinemia]], and recurrent Infections. Therefore myelokathexis is also known as the W.H.I.M. syndrome. In spite of severe neutropenia (low number of neutrophils) in peripheral blood of myelokathexis patients, their bone marrow is hypercellular and it is 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.
| | ==[[Neutropenia causes|Causes]]== |
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| '''Autoimmune neutropenia''' — most common in infants and young children where the body identifies the neutrophils as enemies and makes [[antibodies|antibody]] to destroy them. This form usually lessens in severity within two years of [[diagnosis]].
| | ==[[Neutropenia differential diagnosis|Differentiating Neutropenia from other Diseases]]== |
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| '''Drug-induced neutropenia''' — Many drugs can cause agranulocytosis (complete absence of white cells) and neutropenia. Many [[chemotherapy|anti-neoplastic drugs]] cause agranulocytosis and neutropenia by bone marrow suppression. Neutropenia and agranulocytosis can also result from [[antibody]] or [[complement system|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. [[Clozapine]], [[procainamide]], anti-thyroid drugs (e.g. [[methimazole]], and [[sulfasalazine]] are at the top of the list of drugs causing this problem, but many others (such as [[antiepileptic]]s) have been implicated.
| | ==[[Neutropenia epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Differential diagnosis of causes of neutropenia== | | ==[[Neutropenia risk factors|Risk Factors]]== |
| Causes can be divided into the following groups:
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| * Decreased production in the [[bone marrow]]:
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| ** [[Hereditary disorder]]s (e.g. congenital neutropenia, [[Cyclic neutropenia]])
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| ** [[Cancer]]
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| ** [[Drugs]]
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| ** [[Radiation]]
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| ** [[cobalamin|Vitamin B<sub>12</sub>]] or [[folate]] deficiency.
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| * Increased destruction:
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| ** [[Aplastic anemia]]
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| ** [[autoimmune disorder|Autoimmune]] neutropenia.
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| ** [[Chemotherapy]]
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| * Marginalisation and sequestration:
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| ** [[dialysis|Hemodialysis]]
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| There is usually a mild neutropenia in [[viral infection]]s.
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| ==Signs and symptoms==
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| Neutropenia can go undetected, but is generally discovered when a patient has developed severe [[infection]]s or [[sepsis]]. Some common infections can take an unexpected course in neutropenic patients; formation of [[pus]], for example, can be notably absent, as this requires circulating neutrophil granulocytes.
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| Some common symptoms of neutropenia include:
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| *[[Fever]]
| | ==[[Neutropenia screening|Screening]]== |
| *Frequent [[infections]] due to lessened ability to fight [[bacterial]] infections
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| *Mouth [[ulcers]]
| | ==[[Neutropenia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| *[[Diarrhea]]
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| *[[Burning sensation when urinating]]
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| *Unusual redness, pain, or [[swelling]] around a wound
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| *[[Sore throat]]
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| *[[Shortness of breath]]
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| *Shaking [[chills]]
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| ==Diagnosis== | | ==Diagnosis== |
| Low neutrophil counts are detected on a [[full blood count]]. A [[peripheral blood smear]] is often useful to evaluate for abnormal morphology of the visible cells, which may help suggest the diagnosis. Evaluation for metabolic abnormalities, genetic causes neutropenia, and/or other underlying metabolic or toxic causes will often follow. When the etiology is uncertain, or serious causes such as malignancy and marrow replacement are suspected, [[bone marrow biopsy]] is often necessary.
| | [[Neutropenia history and symptoms| History and Symptoms]] | [[Neutropenia physical examination | Physical Examination]] |[[Neutropenialaboratory findings|Laboratory Findings]] | [[Neutropenia chest x ray|Chest X Ray]] | [[NeutropeniaCT|CT]] | [[Neutropenia MRI|MRI]] | [[Neutropenia ultrasound|Ultrasound]] | [[Neutropenia other imaging findings|Other Imaging Findings]] | [[Neutropenia other diagnostic studies|Other Diagnostic Studies]] |
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| | ==Treatment== |
| | [[Neutropenia medical therapy|Medical Therapy]] | [[Neutropenia surgery|Surgery]] | [[Neutropenia primary prevention|Primary Prevention]] | [[Neutropenia secondary prevention|Secondary Prevention]] | [[Neutropenia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Neutropenia future or investigational therapies|Future or Investigational Therapies]] |
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| ==Therapy==
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| There is no ideal therapy for neutropenia, but recombinant [[Granulocyte-colony stimulating factor|G-CSF]] (granulocyte-colony stimulating factor) can be effective in chemotherapy patients, in patients with congenital forms of neutropenia including severe congenital neutropenia, autosomal recessive Kostmann's syndrome, cyclic neutropenia, myelokathexis, and some other causes...
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| ==See also== | | ==Case Studies== |
| | [[Neutropenia case study one|Case#1]] |
| | ==Related Chapters== |
| * [[Aplastic anemia]] | | * [[Aplastic anemia]] |
| * [[Pancytopenia]] | | * [[Pancytopenia]] |
| * [[Thrombocytopenia]] | | * [[Thrombocytopenia]] |
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| ==References==
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| {{reflist|2}}
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| {{Hematology}} | | {{Hematology}} |