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 1.5 h 109/l. It could be classified as mild, moderate and severe, based on the following absolute neutrophil count: 1-1.5 h 109/l, 0.5-1 h 109/l, and < 0.5 h 109/l. 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.