Adverse drug reactions aplastic anemia

Should the [adverse drug reaction] be dramatic and rapidly discovered, such as torsades de pointes, aplastic anemia, or rhabdomyolysis, there will be a torrent of recriminations about why this was not discovered earlier during the [pieapproveil] clinical testing. The correct response is that the testing of only 5,000 to 10,000 patients could not pick up such a rare event. This response is usually lost in the clamor. 

The most serious adverse reaction associated with these drugs is agranulocytosis (decrease in the number of white blood cells [eg, neutrophils, basophils, and eosinophils]). Reactions observed with agranulocytosis include hay fever, sore throat, skin rash, fever, or headache Other major reactions include exfoliative dermatitis, granulocytopenia, aplastic anemia, hypoprothrombinemia, and hepatitis. Minor reactions, such as nausea, vomiting, and paresthesias, also may be seen. 

In some drug reactions, several of these hypersensitivity responses may present simultaneously. Some adverse reactions to drugs may be mistakenly classified as allergic or immune when they are actually genetic deficiency states or are idiosyncratic and not mediated by immune mechanisms (eg, hemolysis due to primaquine in glucose-6-phosphate dehydrogenase deficiency, or aplastic anemia caused by chloramphenicol). 

Blood dyscrasias, mostly dose independent, are among the most important allergic-type adverse reactions to drugs. Aplastic anemia is a serious but rare (presumably) idiosyncratic reaction. It has been reported in association with chloramphenicol, quinacrine, phenylbutazone, mephenytoin, gold compounds, and potassium chlorate. Hemolytic anemia, thrombocytopenia, and agranulocytosis may result from an unusual, acquired sensitivity to a variety of widely used drugs including aminopyrine, phenylbutazone, phenothiazines, propylthiouracil, diphenylhydantoin, penicillins, chloramphenicol, sulfisoxazole, and tolbutamide. 

By most reports, idiosyncratic drug-induced hematologic disorders are rare. Relatively few epidemiologic studies have addressed the actual incidence of these adverse reactions. A report from The Netherlands estimated the incidence of drug-associated agranulocytosis as 1.6 to 2.5 cases per million inhabitants per year. Similar results were found in epidemiologic studies conducted in Thailand and BraziU Older data from a study conducted in Europe and Israel estimated the incidences of aplastic anemia and agranulocytosis to be 0.5 and 3.1 cases per million per year, respectively. ... 

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