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an acute blood disorder (often caused by radiation or drug therapy) characterized by severe reduction in granulocytes (同)agranulosis, granulocytopenia
tending to discourage (especially of prices); "the price was prohibitive" (同)prohibitory

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禁止する,禁制の / (価格が)手がでないほど高い;(顔つきなどから)近づきにくい

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/27 07:52:10」(JST)

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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.^[1]^[2] It is 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 suppressed immune system.

In agranulocytosis, the concentration of granulocytes (a major class of white blood cells that includes neutrophils, basophils, and eosinophils) drops below 500 cells/mm³ of blood.

Classification

The term "agranulocytosis" derives from the Greek: a, meaning without; granulocyte, a particular kind of white blood cell (containing granules in its cytoplasm); and osis, meaning condition [esp. disorder]. Consequently, agranulocytosis is sometimes described as "no granulocytes", but a total absence is not required for diagnosis. 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, is sometimes preferred 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.

The terms agranulocytosis, granulocytopenia and neutropenia are sometimes used interchangeably. Agranulocytosis implies a more severe deficiency than granulocytopenia. Neutropenia indicates a deficiency of neutrophils (the most common granulocyte cell) only.

To be precise, neutropenia is the term normally used to describe absolute neutrophil counts (ANCs) of less than 500 cells per microlitre, whereas agranulocytosis is reserved for cases with ANCs of less than 100 cells per microlitre.

The following terms can be used to specify the type of granulocyte referenced:

Inadequate numbers of neutrophils: neutropenia (most common)
Inadequate numbers of eosinophils: eosinopenia (uncommon)
Inadequate numbers of basophils: basopenia (very rare)

Signs and symptoms

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). Septicemia may also progress rapidly.

Causes

A large number of drugs^[3] have been associated with agranulocytosis, including Aubagio immunomodulatory agent with anti-inflammatory properties, antiepileptics, antithyroid drugs (carbimazole, methimazole, and propylthiouracil), antibiotics (penicillin, chloramphenicol and co-trimoxazole), cytotoxic drugs, gold, NSAIDs (indomethacin, naproxen, phenylbutazone, metamizole), mebendazole, allopurinol^[4] the antidepressant mirtazapine, and some antipsychotics (the atypical antipsychotic clozapine^[5]). Clozapine users in the United States, Canada, and the UK must be nationally registered for monitoring of low WBC and absolute neutrophil counts (ANC).

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.

The Centers for Disease Control 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.^[6] Levamisole is an antihelminthic (i.e. deworming) drug used in animals. The reason for adding levamisole to cocaine is unknown,^[7] although it can be due to their similar melting points and solubilities.

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.

To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasia and leukemias. This requires a bone marrow examination that shows normocellular (normal amounts and types of cells) blood marrow with underdeveloped promyelocytes. These underdeveloped promyelocytes, if fully matured, would have been the missing granulocytes.

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.

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.

References

^ eMedicine/Stedman Medical Dictionary
^ Neutropenia at eMedicine
^ Andersohn F, Konzen C, Garbe E (May 2007). "Systematic review: agranulocytosis induced by nonchemotherapy drugs". Ann. Intern. Med. 146 (9): 657–65. doi:10.7326/0003-4819-146-9-200705010-00009. PMID 17470834.
^ Elisa Mari,Franco Ricci,Davide Imberti,Massimo Gallerani (June 2011). "Agranulocytosis: an adverse effect of allopurinol treatment". Italian Journal of Medicine 5 (2): 120–3. doi:10.1016/j.itjm.2011.02.006.
^ Diaz, Jaime (1996). How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall. ISBN 0132815605.
^ U.S. Department of Justice; National Drug Intelligence Center (February 2010). "Colombian Cocaine Producers Increase Use of a Harmful Cutting Agent". National Drug Threat Assessment 2010.
^ "Agranulocytosis associated with cocaine use — four States, March 2008–November 2009". MMWR Morb. Mortal. Wkly. Rep. 58 (49): 1381–5. December 2009. PMID 20019655. Cited in Hsu, Jeremy (18 December 2009). "Majority of U.S. Cocaine Supply Cut with Veterinary Deworming Drug". Popular Science.

UpToDate Contents

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1. 薬剤誘発性の好中球減少および無顆粒球症 drug induced neutropenia and agranulocytosis
2. 小児および思春期における好中球減少症の概要 overview of neutropenia in children and adolescents
3. 原因不明の好中球減少症を有する成人に対するアプローチ approach to the adult with unexplained neutropenia
4. 非化学療法誘導性好中球減少症を有する成人のマネージメント management of the adult with non chemotherapy induced neutropenia
5. チオナミドの薬理学および毒性 pharmacology and toxicity of thionamides

English Journal

Effect of Aminoglutethimide on Neutrophils in Rats: Implications for Idiosyncratic Drug-Induced Blood Dyscrasias.

Ng W, Uetrecht J.SourceDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto , Toronto, Ontario, Canada M5S 3M2.
Chemical research in toxicology.Chem Res Toxicol.2013 Aug 9. [Epub ahead of print]
Aminoglutethimide (AMG) is an aromatic amine aromatase inhibitor associated with a high incidence of idiosyncratic blood dyscrasias, especially agranulocytosis. Animal models of idiosyncratic drug reactions (IDRs) represent essential tools to study these reactions; however, there is currently no val
PMID 23889370

A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes.

Cermak J, Jonasova A, Vondrakova J, Cervinek L, Belohlavkova P, Neuwirtova R.SourceInstitute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Praha, Prague, Czech Republic. Electronic address: cermak@uhkt.cz.
Leukemia research.Leuk Res.2013 Aug 9. pii: S0145-2126(13)00248-8. doi: 10.1016/j.leukres.2013.07.021. [Epub ahead of print]
One hundred thirteen patients with myelodysplastic syndromes (MDS) with <10% of bone marrow blasts received either deferiprone in a daily dose of 40-90mg/kg (48 patients) or deferasirox in a daily dose of 10-40mg/kg (65 patients). Median duration of treatment was 10,9 months for deferiprone and 1
PMID 23937987

Agranulocytosis with deferiprone treatment of superficial siderosis.

Huprikar N, Gossweiler M, Callaghan M, Bunge P.SourceInternal Medicine Department, Madigan Army Medical Center, Tacoma, Washington, USA.
BMJ case reports.BMJ Case Rep.2013 Aug 7;2013. pii: bcr2013010099. doi: 10.1136/bcr-2013-010099.
Superficial siderosis of the central nervous system is a rare neurological disorder caused by deposits of haemosiderin on subplial brain matter. Characterised by a thin dark layer surrounding the brain stem, cerebellum and cortical fissures on the T2-weighted MRI, symptoms include sensorineural hear
PMID 23925681

Clozapine and agranulocytosis: re-assessing the risks.

Drew L.SourceSenior Specialist in Psychiatry, The Canberra Hospital and Australian National University, Canberra, ACT, Australia.
Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists.Australas Psychiatry.2013 Aug;21(4):335-7. doi: 10.1177/1039856213491990. Epub 2013 Jun 26.
OBJECTIVE: The aim of the study was to estimate the maximum incidence of agranulocytosis which clozapine would have caused between 2006 and 2010 had there been no blood monitoring system; and to determine the number of clozapine-associated cases of agranulocytosis and related deaths recorded between
PMID 23804114

Japanese Journal

新規抗血小板薬プラスグレルを併用したdual antiplatelet therapy 下での頚動脈ステント留置術

山本優,福田仁,半田明,山田大輔,黒﨑義隆,沈正樹,山形専
脳神経血管内治療 advpub(0), 2015
要旨: 【目的】頚動脈ステント留置術（carotid artery stenting; CAS）の周術期は，脳血管領域に保険適応のある抗血小板薬のうち2 剤を併用して血栓症予防を行うことが一般的である．今回，既存薬剤による副作用のため，新規抗血小板薬のプラスグレルを併用しCAS を施行した．【症例】症候性内頚動脈狭窄症を有する70 歳男性に対し，クロピドグレル・シロスタゾールが無顆粒球症の被疑薬の …
NAID 130005097362

多種免疫異常症を合併した二次性生着不全に対し再臍帯血移植を行い救命しえた急性骨髄性白血病

森美奈子,米澤昭仁,北川智也 [他],佐々木裕哉,大中貴史,今田和典
臨床血液 56(7), 889-894, 2015
64歳女性，急性骨髄性白血病に対し非寛解で臍帯血移植を行った。臍帯血は男児でHLA血清型6座一致であり，速やかな3系統の生着が得られ，day28ドナー型完全キメラであった。Day82混合キメラ(XX 8.8%)となり，day96よりtacrolimusを減量開始しday123に中止した。経過中GVHDは認めなかった。Day138汎血球減少，無顆粒球症を認め，day153二次性生着不全と診断。また免 …
NAID 130005093114

TS-1®服用1コース目に重篤な骨髄抑制をきたした2例

髙岡亮裕,寺田友紀,宇和伸浩 [他],毛利武士,貴田紘太,阪上雅史
耳鼻咽喉科臨床 108(5), 397-402, 2015
… On the basis of result of the autopsy, the sepsis following agranulocytosis was considered to be the cause of death.A 70-year-old-man with hypopharyngeal cancer of the right piriform sinus (cT4aN2bM0) underwent operation with a total laryngopharyngectomy. …
NAID 130005067354

造血系副作用 : 無顆粒球症,薬剤性貧血,血小板減少症,再生不良性貧血 (第5土曜特集くすりの副作用のすべて) -- (病態からみたくすりの副作用)

檀和夫
医学のあゆみ 251(9), 720-725, 2014-11-29
NAID 40020276887

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★リンクテーブル★

リンク元	「prohibitive」「無顆粒球症」「顆粒球減少症」「granulocytopenia」
拡張検索	「methimazole-induced agranulocytosis」

「prohibitive」

Agranulocytosis
Classification and external resources
Specialty	Hematology
ICD-10	D70
ICD-9-CM	288.0
DiseasesDB	8994
MedlinePlus	001295
MeSH	D000380
	[edit on Wikidata]

　　[★]

adj.

禁止する、謹製の。(値段が)ひどく高い、(税が)極端に重い。勝利(など)が間違いない

clozapine is generally prescribed only after several other alternative neuroeptic medication have failed, because of the possibility of agranulocytosis and the drug's prohibitive cost.