Perspectives on hydrogen peroxide and drug-induced hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency

G-6-PD-deficiency is a genetic disorder of erythrocytes in which the inability of affected cells to maintain NAD(P)H levels sufficient for the reduction of oxidized glutathione results in inadequate detoxification of hydrogen peroxide through glutathione peroxidase. Although a variety of free-radical species may be produced during the interaction of xenobiotic agents with erythrocytes and hemoglobin, the inability to destroy peroxides seems to be the hallmark of the disease. Colloid osmotic hemolysis is seldom observed in this disorder and it is possible that hydroxyl radicals derived from peroxide damage both lipid and protein constituents of the plasma membrane so that its intrinsic mechanical properties are altered. Erythrocytes with damaged membranes become less deformable and may be subjected to mechanical entrapment in the microcirculation. Ultimate recognition of damaged cell and sequestration by phagocytes leads to anemia.