Agranulocytosis

Most cases of agranulocytosis occur within the first 8 to 12 weeks of therapy in 0.2%-0.4% of patients. Although most patients recover, it may be fatal. Agranulocytosis is characterized by a neutrophil count of less than 0.5 x 109/l. The mechanism of dapsone-induced agranulocytosis is unclear. The hydroxylamine metabolite of dap-sone is known to be toxic to human bone marrow and to human mononuclear cells in vitro. It is also produced by neutrophils in vitro during the respiratory burst. In addition, red blood cells seem to be involved. When exposed to hydroxylamine, erythrocytes liberate this metabolite and kill mononuclear leukocytes in vitro. Hydroxylamine binds strongly to red blood cells and reaches the bone marrow, where it can damage granulocyte precursors and lead to potentially fatal agranulocytosis (Coleman 1993, Katz 1999, Zhu and Stiller 2001).

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