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| '''For patient information click [[Agranulocytosis (patient information)|here]]'''
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| {{DiseaseDisorder infobox | | | {{DiseaseDisorder infobox | |
| Name = Agranulocytosis | | | Name = Agranulocytosis | |
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| ICD9 = {{ICD9|288.0}} | | | ICD9 = {{ICD9|288.0}} | |
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| | '''For patient information click [[Agranulocytosis (patient information)|here]]''' |
| {{Agranulocytosis}} | | {{Agranulocytosis}} |
| {{CMG}} | | {{CMG}} |
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| ==Overview== | | ==[[Agranulocytosis overview|Overview]]== |
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| '''Agranulocytosis''', also known as '''Agranulosis''' or '''Granulopenia''', is an acute condition involving a severe and dangerous [[leukopenia]] (lowered [[white blood cell]] count), most commonly of [[neutrophils]] causing a [[neutropenia]] in the circulating blood.<ref>[http://www.emedicine.com/asp/dictionary.asp?keyword=agranulocytosis eMedicine/Stedman Medical Dictionary ]</ref><ref>http://www.emedicine.com/MED/topic82.htm</ref> It represents a severe lack of one major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to their [[Immunodeficiency|suppressed immune system]].
| | ==[[Agranulocytosis historical perspective|Historical Perspective]]== |
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| In agranulocytosis, the concentration of [[granulocyte]]s (a major class of [[white blood cells]] that includes neutrophils, [[basophils]], and [[eosinophils]]) drops below 100 cells/mm³ of blood, which is less than 5% of the normal value.
| | ==[[Agranulocytosis classification|Classification]]== |
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| ==Classification== | | ==[[Agranulocytosis pathophysiology|Pathophysiology]]== |
| The term "agranulocytosis" derives from the Greek: ''a'', meaning ''without''; ''granulocyte'', a particular kind of cell; ''osis'', meaning ''condition'' [esp. ''disorder'']. Consequently, agranulocytosis is sometimes described as "no [[granulocyte]]s", but a total absence is not required for diagnosis.
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| However, "-osis" is commonly used in blood disorders to imply cell proliferation (such as in "leukocytosis"), while "-penia" to imply reduced cell numbers (as in "leukopenia"); for these reasons granulopenia is a more etymologically consistent term and as such should be preferred compared to "agranulocytosis" (which can be misinterpreted as "agranulocyt-osis", meaning proliferation of agranulocytes (i.e. lymphocytes and monocytes). Despite this, "agranulocytosis" remains the most widely used term for the condition.
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| The terms ''agranulocytosis'', ''[[granulocytopenia]]'' and ''[[neutropenia]]'' are sometimes used interchangeably. Agranulocytosis implies a more severe deficiency than granulocytopenia. Neutropenia indicates a deficiency of [[neutrophil]]s (the most common granulocyte cell) only.
| | ==[[Agranulocytosis causes|Causes]]== |
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| To be precise, neutropenia is the term normally used to describe [[absolute neutrophil count]]s (ANC) of less than 500 cells per microlitre, whereas agranulocytosis is reserved for cases with ANC of less than 100 cells per microlitre.
| | ==[[Agranulocytosis differential diagnosis|Differentiating Agranulocytosis from other Diseases]]== |
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| The following terms can be used to specify the type of granulocyte referenced:
| | ==[[Agranulocytosis epidemiology and demographics|Epidemiology and Demographics]]== |
| * Inadequate numbers of [[neutrophil]]s: [[neutropenia]] (most common)
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| * Inadequate numbers of [[eosinophil]]s: [[eosinopenia]] (uncommon)
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| * Inadequate numbers of [[basophil]]s: [[basopenia]] (very rare)
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| ==Signs and symptoms== | | ==[[Agranulocytosis risk factors|Risk Factors]]== |
| Agranulocytosis may be [[asymptomatic]], or may clinically present with sudden fever, rigors and sore throat. [[Infection]] of any organ may be rapidly progressive (e.g., [[pneumonia]], [[urinary tract infection]]). [[Sepsis|Septicemia]] may also progress rapidly.
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| Neutropenia and agranulocytosis are associated with gum diseases, such as [[Bleeding on probing|gingival bleeding]], saliva increase, halitosis, osteoporosis, and destruction of periodontal ligament.{{Citation needed|date=April 2007}}
| | ==[[Agranulocytosis screening|Screening]]== |
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| ==Causes== | | ==[[Agranulocytosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| A large number of drugs<ref>[http://www.annals.org/cgi/reprint/146/9/657.pdf Systematic Review: Agranulocytosis Induced by Nonchemotherapy Drugs], Ann Intern Med. 2007;146:657-665</ref>
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| have been associated with agranulocytosis, including [[antiepileptic]]s, antithyroid drugs ([[carbimazole]], [[methimazole]], and [[propylthiouracil]]), antibiotics ([[penicillin]], [[chloramphenicol]] and [[co-trimoxazole]]), cytotoxic drugs, gold, NSAIDs ([[indomethacin]], [[naproxen]], [[phenylbutazone]], [[metamizole]]), [[mebendazole]], the antidepressant [[mirtazapine]], and some [[antipsychotic]]s (the atypical antipsychotic [[clozapine]]<ref>Diaz, Jaime. How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall, 1996.</ref>). Clozapine users in the US and Canada must be nationally registered for monitoring of low WBC and absolute neutrophil counts (ANC).
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| Although the reaction is generally idiosyncratic rather than proportional, experts recommend that patients using these drugs be told about the symptoms of agranulocytosis-related infection, such as a sore throat and a fever.
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| The [[Centers for Disease Control]] recently traced outbreaks of agranulocytosis among [[cocaine]] users, in the US and Canada between March 2008 and November 2009, to the presence of [[levamisole]] in the drug supply. The [[Drug Enforcement Administration]] reported that, as of February 2010, 71% of seized cocaine lots coming into the US contained levamisole as a [[cutting agent]].<ref>U.S. Department of Justice, National Drug Intelligence Center, ''National Drug Threat Assessment 2010'', [http://www.justice.gov/ndic/pubs38/38661/drugImpact.htm#textbox1 Colombian Cocaine Producers Increase Use of a Harmful Cutting Agent], February 2010.</ref> Levamisole is an [[antihelminthic]] (i.e. deworming) drug used in animals. The reason for adding levamisole to cocaine is unknown,<ref>"Agranulocytosis Associated with Cocaine Use --- Four States, March 2008--November 2009." Centers for Disease Control: Morbidity and Mortality Weekly Report. December 18, 2009/Vol. 58/No. 49 [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5849a3.htm] Cited in Hsu, Jeremy. "Majority of U.S. Cocaine Supply Cut with Veterinary Deworming Drug." Popsci.com. December 18, 2009. [http://www.popsci.com/science/article/2009-12/majority-us-cocaine-supply-cut-veterinary-deworming-drug]</ref> although it can be due to their similar melting points and solubilities.
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| ==Diagnosis== | | ==Diagnosis== |
| The diagnosis is made after a [[complete blood count]], a routine blood test. The absolute neutrophil count in this test will be below 500, and can reach 0 cells/mm³. Other kinds of blood cells are typically present in normal numbers.
| | [[Agranulocytosis history and symptoms|History and Symptoms]] | [[Agranulocytosis physical examination|Physical Examination]] | [[Agranulocytosis laboratory findings|Laboratory Findings]] | [[Agranulocytosis imaging findings|Imaging Findings]] | [[Agranulocytosis other diagnostic studies|Other Diagnostic Studies]] |
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| To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as [[aplastic anemia]], [[paroxysmal nocturnal hemoglobinuria]], [[myelodysplasia]] and [[leukemia]]s. This requires a [[bone marrow examination]] that shows normocellular (normal amounts and types of cells) blood marrow with underdeveloped [[promyelocyte]]s. These underdeveloped promyelocytes, if fully matured, would have been the missing granulocytes.
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| ==Treatment== | | ==Treatment== |
| In patients that have no symptoms of infection, management consists of close monitoring with serial [[blood counts]], withdrawal of the offending agent (e.g., medication), and general advice on the significance of fever.
| | [[Agranulocytosis medical therapy|Medical Therapy]] | [[Agranulocytosis surgery|Surgery]] | [[Agranulocytosis prevention|Prevention]] | [[Agranulocytosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Agranulocytosis future or investigational therapies|Future or Investigational Therapies]] |
| | | ==Case Studies== |
| Infection in patients with low [[white blood cell]] counts is usually treated urgently, and usually includes a broad-spectrum penicillin ([[piperacillin-tazobactam]] or [[Timentin|ticarcillin clavulanate]]) or cephalosporin ([[ceftazidime]]), or [[meropenem]] in combination with [[gentamicin]] or [[amikacin]].{{Citation needed|date=February 2007}}
| | [[Agranulocytosis case study one|Case #1]] |
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| If the patient remains febrile after 4–5 days and no causative organism for the infection has been identified, antibiotics are, in general, changed to a glycopeptide (e.g., [[vancomycin]]), and subsequently an antifungal agent (e.g., [[amphotericin B]]) is added to the regimen.{{Citation needed|date=February 2007}} In agranulocytosis, the use of recombinant G-CSF ([[filgrastim]]) often results in hematologic recovery.{{Citation needed|date=February 2007}}
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| [[Blood transfusion|Transfusion]] of granulocytes would have been a solution to the problem. However, granulocytes live only ~10 hours in the circulation (for days in [[spleen]] or other tissue), which gives a very short-lasting effect. In addition, there are many complications of such a procedure. | |
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| ==Related Chapters== | | ==Related Chapters== |