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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.

Publication ,  Journal Article
Virshup, DM; Zinkham, WH; Sirota, RL; Caughey, WS
Published in: Am J Hematol
June 1983

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 hemolysis in individuals with unstable hemoglobins. Therapeutic doses of PAP administered to a subject with Hb Zürich (His E7 (63) beta leads to 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 beta chain for carbon monoxide is much greater than that of the normal alpha and beta 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 beta subunit of Hb Zürich.

Duke Scholars

Published In

Am J Hematol

DOI

ISSN

0361-8609

Publication Date

June 1983

Volume

14

Issue

4

Start / End Page

315 / 324

Location

United States

Related Subject Headings

  • Smoking
  • Reticulocytes
  • Phenazopyridine
  • Methemoglobin
  • Immunology
  • Humans
  • Hemoglobins, Abnormal
  • Hemoglobins
  • Hematocrit
  • Heinz Bodies
 

Citation

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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. Am J Hematol, 14(4), 315–324. https://doi.org/10.1002/ajh.2830140402
Virshup, D. M., W. H. Zinkham, R. L. Sirota, and W. S. Caughey. “Unique sensitivity of Hb Zürich to oxidative injury by phenazopyridine: reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro.Am J Hematol 14, no. 4 (June 1983): 315–24. https://doi.org/10.1002/ajh.2830140402.
Virshup, D. M., et al. “Unique sensitivity of Hb Zürich to oxidative injury by phenazopyridine: reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro.Am J Hematol, vol. 14, no. 4, June 1983, pp. 315–24. Pubmed, doi:10.1002/ajh.2830140402.
Journal cover image

Published In

Am J Hematol

DOI

ISSN

0361-8609

Publication Date

June 1983

Volume

14

Issue

4

Start / End Page

315 / 324

Location

United States

Related Subject Headings

  • Smoking
  • Reticulocytes
  • Phenazopyridine
  • Methemoglobin
  • Immunology
  • Humans
  • Hemoglobins, Abnormal
  • Hemoglobins
  • Hematocrit
  • Heinz Bodies