Unique sensitivity of Hb Zürich to oxidative injury by phenazopyridine: Reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro
✍ Scribed by David M. Virshup; William H. Zinkham; Ronald L. Sirota; Winslow S. Caughey
- Book ID
- 102698008
- Publisher
- John Wiley and Sons
- Year
- 1983
- Tongue
- English
- Weight
- 956 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0361-8609
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✦ Synopsis
Phenazopyridine (PAP) causes a hemolytic anemia in normal individuals who receive an overdose or in patients with decreased renal function given therapeutic doses. There are no reports of PAP-induced hernolysis in individuals with unstable hemoglobins. Therapeutic doses of PAP administered to a subject with Hb Zurich (His E7 (63) 0-Arg) caused a severe hemolytic anemia with many large Heinz bodies appearing in the red cells.
Incubation of whole blood from three asymptomatic Hb Zurich subjects with PAP at a molar ratio of PAP/Hb of 1.3/1 produced a moderate to marked increase in methemoglobin (MHb) and Heinz body formation accompanied by a slight to moderate decrease. in levels of reduced glutathione. The rates of MHb formation were proportional to the concentration of PAP. In two of the subjects the rates of formation of Heinz bodies and MHb were substantially higher than in the third subject. Red cells from five normal adults were not affected. In Hb Zurich red cells the affinity of the abnormal 0 chain for carbon monoxide is much greater than that of the normal a and 0 chains. The two subjects with higher rates of MHb and Heinz body formation were nonsmokers with in vivo carboxyhemoglobin (HbCO) levels of 4-6%. The third subject with low rates of MHb and Heinz body formation was a smoker with in vivo HbCO levels of 15-1896. Increasing levels of HbCO from 8.2% to 14.3% by the in vitro addition of CO caused a marked reduction in the rate of Heinz body formation and a moderate decrease in MHb formation. Rates of MHb formation similar to those observed in normal red cells occurred at HbCO percentages of 89.2 and 99.2. Red cells containing Hb Zurich are extremely sensitive to oxidative injury by PAP, either in vivo or in vitro. The degree of oxidative injury diminishes as the level of HbCO