Agranulocytosis, also known asagranulosis orgranulopenia, is an acute condition involving a severe and dangerous loweredwhite blood cell count (leukopenia, most commonly ofneutrophils) and thus causingneutropenia in the circulating blood.[1] It is a severe lack ofone major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to theirsuppressed immune system.
In agranulocytosis, the concentration ofgranulocytes (a major class of white blood cells that includes neutrophils,basophils, andeosinophils) drops below 200 cells/mm3 of blood.
Agranulocytosis may beasymptomatic, 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 may also progress rapidly.[citation needed]
A large number of drugs[2] have been associated with agranulocytosis, includingantiepileptics (such ascarbamazepine andvalproate), antithyroid drugs (carbimazole,thiamazole, andpropylthiouracil), antibiotics (penicillin,chloramphenicol andtrimethoprim/sulfamethoxazole),H2 blockers (cimetidine, famotidine, nizatidine, ranitidine),[3] ACE inhibitors (benazepril),cytotoxic drugs,gold salts, analgesics (aminophenazone,indomethacin,naproxen,phenylbutazone,metamizole),mebendazole,allopurinol,[4] the antidepressantsmianserin andmirtazapine, and someantipsychotics.[5] The atypical antipsychoticclozapine in particular is largely restricted to treatment-resistant cases and mandatory blood count monitoring in most countries.[6]
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.[citation needed]
TheCenters for Disease Control and Prevention traced outbreaks of agranulocytosis amongcocaine users, in the US and Canada between March 2008 and November 2009, to the presence oflevamisole in the drug supply. TheDrug Enforcement Administration reported that, as of February 2010, 71% of seized cocaine lots coming into the US contained levamisole as acutting agent.[7] Levamisole is anantihelminthic (i.e. deworming) drug used in animals. The reason for adding levamisole to cocaine hydrochloride is unknown,[8] although it is likely due to their similar melting points, solubilities, and appearance.
The diagnosis is made after acomplete 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 asaplastic anemia,paroxysmal nocturnal hemoglobinuria,myelodysplasia andleukemias. This requires abone marrow examination that shows normocellular (normal amounts and types of cells) blood marrow with underdevelopedpromyelocytes. These underdeveloped promyelocytes, if fully matured, would have been the missing granulocytes.[citation needed]
The term "agranulocytosis" derives from the Greek:a, meaning without;granulocyte, a particular kind of white blood cell (containing granules in its cytoplasm); andosis, 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, granulocytopenia 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.[citation needed]
The terms agranulocytosis,granulocytopenia andneutropenia are sometimes used interchangeably. Agranulocytosis implies a more severe deficiency than granulocytopenia. Neutropenia indicates a deficiency ofneutrophils (the most common granulocyte cell) only.[citation needed]
To be precise, neutropenia is the term normally used to describeabsolute 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.[citation needed]
The following terms can be used to specify the type of granulocyte referenced:
In a general sense the pathogenesis of neutropenia can be divided into two categories;
In patients that have no symptoms of infection, management consists of close monitoring with serial blood counts, cessation of the offending agent (e.g., medication), and general advice on the significance of fever.Transfusion of granulocytes would be 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.[citation needed]
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