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Unique sensitivity of Hb Zürich to oxidative injury by phenazopyridine: Reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro
Abstract
Phenazopyridirie (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 hemolysis in individuals with unstable hemoglobins. Therapeutic doses of PAP administered to a subject with Hb Zürich (His E7 (63) β→ Arg) caused a severe hemolytic anemia with many large Heinz bodies appearing in the red cells. Incubation of whole blood from three asymptomatic Hb Zürich 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 Zürich red cells the affinity of the abnormal β chain for carbon monoxide is much greater than that of the normal α and β 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 15–18%. 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 Zürich 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 increases, a phenomenon that is enhanced by preferential binding of CO to the abnormal β subunit of Hb Zürich.
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“In haemoglobinopathies such as Hb Zurich, which is associated with haemolysis, CO may have a beneficial effect on haemolysis: as a result of the 65-fold increase in the affinity of the abnormal beta-globin chain of Hb Zurich for CO, the molecule is stabilized and exhibits resistance to oxidative injury, a decreased rate of haemolysis and a marked increase in oxygen affinity (Virshup et al., 1983;Z”
From Anaemia and cigarette smoking (2008) · cites this paper as Virshup et al., 1983
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Research works printed but not linked: 27
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Cited by
LEIFERT, J. A. (2008) · International Journal of Laboratory Hematology · doi:10.1111/j.1751-553x.2008.01067.x · Cited by 83
Metadata
- Authors
- Virshup, D. M., Zinkham, W. H., Sirota, R. L., & Caughey, W. S.
- Venue
- American Journal of Hematology
- Publisher
- Wiley
- Published
- 1983-06
- Volume
- 14
- Issue
- 4
- Pages
- 315-324
- ISSN
- 0361-8609
- 1096-8652
- Cited by
- 7
- References
- 0
- Language
- en
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- Virshup, D. M., Zinkham, W. H., Sirota, R. L., & Caughey, W. S. (1983). Unique sensitivity of Hb Zürich to oxidative injury by phenazopyridine: Reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro. American Journal of Hematology. https://doi.org/10.1002/ajh.2830140402
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