INTRACELLULAR PRECIPITATION OF HEMOGLOBIN BY HEAT: IN VIVO AND IN VITRO STUDIES

Abstract

A patient with hemoglobin Zürich (Hb Z) had a viral-related fever of 39-41°C for 5 days. The hematocrit decreased from 45-25, plasma hemoglobin was 144 mg%, Heinz bodies (H.B.) appeared in 12-18% of the erythrocytes (RBC), and there was moderate reticulocytosis. There was no history of exposure to oxidants. These observations led to a study of the effects of temperatures in the clinical range of fever on the solubilities of Hb Z and normal hemoglobin (Hb A) in intact RBC. Whole blood from 25 normal adults and 4 Hb Z pts was incubated at 37 and 41°C. After incubation, H.B. were defined by mixing equal parts of blood and rhodanile blue for 2 minutes and making dry films. The % of H.B. in Hb A RBC at 37°C for 3, 6, 12, and 24 hrs was 0, 0, 0, and 49.5±19.1%; in Hb Z - 0, 5-5, 63.6, and 99.2%. The %'s at 41°C were 0, 15.6, 59.4±25.6, and 100 in Hb A RBC; and 24.0, 74.9, 100, and 100 for Hb Z RBC. Hb Z in the red cells did not decrease until 3-6 hrs after the appearance of H.B. The % of Hb A₂ remained constant. Progressive precipitation of Hb in Hb Z and Hb A RBC was accompanied by increased formation of methemoglobin, a marked decrease in reduced glutathione and hexokinase activity, and a moderate decrease in glucose-6-phosphate dehydrogenase and pyruvate kinase activities. Thermal denaturation of hemoglobin may be a cause of fever-related anemia in pts with unstable hemoglobins. Also measurement of H.B. formation in heat-treated whole blood is a sensitive and simple technique for defining Hb Z and possibly other unstable hemoglobins.

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