NEUTROPENIA INDUCED BY NON-CYTOTOXIC DRUGS
Abstract
Polymorphonuclear neutrophils make about 60-70% of all leucocytes in adults. Neutropenia is defined by neutrophil count below 1500 cells/mm3. It could be classified as mild, moderate and severe, based on the following absolute neutrophil count: 1000-1500 cells/mm3, 500-1000 cells/mm3, and <500 cells/mm3. Incidence of drug-induced neutropenia is 3-10 cases per million.
Drug-induced neutropenia emerges suddenly, and develops a few hours to 1-2 days after administration of the offending drug. There are several mechanisms of neutropenia induced by non-cytotoxic drugs: (1) drug binding to neutrophil membrane, formation of hapten and induction of immune response which destroys neutrophil; (2) induction of neutrophil apoptosis; (3) formation of immune complexes; (4) induction of autoantibodies and complement activation with destruction of neutrophils; (5) dose-dependent inhibition of granulopoesis; and (6) direct toxic effect on myeloid precursors.
Treatment of patients with drug-induced neutropenia consists of the offending drug discontinuation, maintenance of strict hygiene and administration of granulocyte-colony stimulating factors in the case of severe neutropenia.
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