Drug-induced agranulocytosis

Abstract

Agranulocytosis is a rare but potentially serious adverse side effect of many drugs. Although it was recognised as an idiosyncratic type of drug reaction more than 50 years ago, its pathogenesis is still not fully understood. Drug-related antibodies are responsible for the neutropenia in the so-called 'immune' or 'aminopyrine' type of agranulocytosis. In contrast to former assumptions, the disappearance of leucocytes is not only due to rapid destruction of circulation cells, but it can result also from failure of the production of granulopoetic cells. In some other groups of drugs there is no evidence of immune-mediated disease, but direct toxicity to bone marrow cells has been observed using biochemical methods or inhibition of the growth of granulopoetic colonies in semisolid culture media. Until now it has not been possible to define the enzymatic abnormality which could explain this metabolic type of idiosyncrasy. The quantification of the incidence of potentially drug-induced agranulocytosis in general, and in particular its association with single drugs, requires studies on large populations and the use of strict epidemiological methodology to prevent reporting of grossly biased results. Data from recent case control studies show definitely lower risks for some relevant groups of drugs than formerly appreciated. As expected, agranulocytosis has been observed in association with some recently introduced drugs. This underlines the necessity for continued postmarketing monitoring of potential haematological side effects and for further case control studies to furnish data to aid prescribing physicians and health authorities in decision-making.