Drug-induced Hemolytic Anemia

Abstract

Sixteen consecutive cases of drug-induced hemolytic anemia were observed over a period of 2 1/2 years. All patients were Caucasians. The responsible drugs were sulfonamides in 11 cases, 1-phenylsemicarbazide (Cryogenine) in 1, and N1-DL-serine-N2-isopropylhydrazide (RO4-1038) in 4. Serial peripheral blood studies, Heinz-body counts, red-cell fragilities, Coombs'' tests, red-cell glucose-6-phosphate dehydrogenase (G6PD) activity, and glutathione (GSH) stability were determined. Survival of Cr51-tagged autologous red cells was followed in 3 cases. It was found that 15 of the 16 patients had normal or slightly increased red-cell G6PD activity and stable red-cell GSH content, although in 5 of these patients red-cell GSH content was slightly below normal. Very low red-cell GSH was found in 1 Ashkenazic Jewess, in whom G6PD activity could not be determined but whose son showed erythrocyte G6PD deficiency and GSH instability. Heinz bodies were present in the red cells of 11 of 14 patients, and disappeared rapidly from the circulation after withdrawal of the offending drug. Osmotic fragility was increased in 4 and normal in 9, mechanical fragility was increased in 5 and normal in 5; Coombs'' tests were negative in all of 14 patients. Survival of autologous Cr51-tagged red cells was slightly shortened in the 3 patients in whom it was determined. It was concluded that hemolytic anemia due to oxidant drugs is not uncommon in subjects with red cells not deficient in G6PD. The majority of cases followed sulfonamide administration. Overdosage and impaired renal function were etiological factors in some patients, but the mechanism of development of the hemolytic anemia in non-G6PD-deficient subjects requires further investigation.