Acetylsalicylic acid-induced hemolysis and its mechanism

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Abstract

Acetylsalicylic acid (ASA) is known to cause severe hemolytic anemia in some glucose-6-phosphate-dehydrogenase-deficient (G-6-PD-deficient) individuals. To study its mechanism, erythrocytes from an ASA-sensitive patient were transfused into a normal compatible recipient. The administration of 2,5-dihydroxybenzoic (gentisic) acid, a known ASA metabolite with redox properties, to the recipient resulted in a marked decrease in the survival of the patient's erythrocytes. Similar studies with red cells from individuals with A- and Mediterranean variants of G-6-PD revealed no alteration in the erythrocytes' survival. Further studies disclosed that both salicylate and gentisate competitively inhibited the G-6-PD from the ASA-sensitive patient resulting in a marked change in the Km for NADP. These drugs also inhibited the A- and Mediterranean variants of G-6-PD. The magnitude of inhibition, however, was comparatively small and not different from that observed with a normal enzyme.

Authors

N. T. Shahidi, D. W. Westring