Acetylsalicylic acid--induced hemolysis and its mechanism

• Published in: The Journal of clinical investigation Vol. 49; no. 7; pp. 1334 - 1340
• Main Authors: Shahidi, N T, Westring, D W
• Format: Journal Article
• Language: English
• Published: United States 01-07-1970
• Subjects: Adolescent; Anemia, Hemolytic - chemically induced; Aspirin - toxicity; Child; Erythrocyte Aging - drug effects; Erythrocytes - drug effects; Gentisates - toxicity; Glucosephosphate Dehydrogenase - antagonists & inhibitors; Glucosephosphate Dehydrogenase Deficiency - blood; Humans; Male
• ISSN: 0021-9738
• DOI: 10.1172/jci106349

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 K(m) 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. The above studies suggested that enzyme inhibition by salicylate and gentisate may play an important role in ASA-induced hemolysis. Such an inhibition would further curtail NADPH regeneration, rendering the cells more vulnerable to oxidants. In this connection, gentisate seems to play a major role in ASA-induced hemolysis for it is both a G-6-PD inhibitor and an "oxidant."