Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1969 Aug;48(8):1376–1386. doi: 10.1172/JCI106103

Erythrocytosis associated with hemoglobin Rainier: oxygen equilibria and marrow regulation

John W Adamson 1,2,3, Julian T Parer 1,2,3, George Stamatoyannopoulos 1,2,3, S Heinenberg 1,2,3
PMCID: PMC322364  PMID: 5796352

Abstract

Hemoglobin Rainier (β145 tyrosine→histidine) is an abnormal hemoglobin associated with increased oxygen affinity, decreased heme-heme interaction, presence of a Bohr effect, and erythrocytosis, but without obvious clinical sequelae.

Regulation of erythropoiesis was studied in affected members of families having either hemoglobin Rainier or Yakima, abnormal hemoglobins associated with erythrocytosis.

Apart from the elevated but stable hemoglobin concentration and red cell mass, parameters of red cell production in the subjects were normal. Initially normal values of erythropoietin excretion were increased by phlebotomy indicating a significant hypoxic stress at an otherwise normal hematocrit. This stress led to increased reticulocyte production and an eventual return to the prephlebotomy hematocrit. The erythrocytosis in carriers of hemoglobins Rainer and Yakima appears to be secondary to the increased oxygen affinity and this, with the response to phlebotomy, is consistent with the postulate that the renal sensor tissue regulating erythropoietin production is primarily influenced by the oxygen tensions of venous rather than arterial blood.

Full text

PDF
1384

Images in this article

1378Image
on p.1378

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson J. W., Alexanian R., Martinez C., Finch C. A. Erythropoietin excretion in normal man. Blood. 1966 Sep;28(3):354–364. [PubMed] [Google Scholar]
  2. Adamson J. W., Finch C. A. Mechanisms of erythroid marrow activation. Trans Assoc Am Physicians. 1966;79:419–425. [PubMed] [Google Scholar]
  3. Adamson J. W. The erythropoietin-hematocrit relationship in normal and polycythemic man: implications of marrow regulation. Blood. 1968 Oct;32(4):597–609. [PubMed] [Google Scholar]
  4. Alexanian R. Urinary excretion of erythropoietin in normal men and women. Blood. 1966 Sep;28(3):344–353. [PubMed] [Google Scholar]
  5. BETHELL F. H., LINMAN J. W. The plasma erythropoietic-stimulating factor in man; observations on patients with polycythemia vera and secondary polycythemia. J Lab Clin Med. 1957 Jan;49(1):113–127. [PubMed] [Google Scholar]
  6. BETKE K., MARTI H. R., SCHLICHT I. Estimation of small percentages of foetal haemoglobin. Nature. 1959 Dec 12;184(Suppl 24):1877–1878. doi: 10.1038/1841877a0. [DOI] [PubMed] [Google Scholar]
  7. BRECHER G., SCHNEIDERMAN M., WILLIAMS G. Z. Evaluation of electronic red blood cell counter. Am J Clin Pathol. 1956 Dec;26(12):1439–1449. doi: 10.1093/ajcp/26.12.1439. [DOI] [PubMed] [Google Scholar]
  8. CONTOPOULOS A. N., MCCOMBS R., LAWRENCE J. H., SIMPSON M. E. Erythropoietic activity in the plasma of patients with polycythemia vera and secondary polycythemia. Blood. 1957 Jul;12(7):614–619. [PubMed] [Google Scholar]
  9. Charache S., Weatherall D. J., Clegg J. B. Polycythemia associated with a hemoglobinopathy. J Clin Invest. 1966 Jun;45(6):813–822. doi: 10.1172/JCI105397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DONOHUE D. M., MOTULSKY A. G., GIBLETT E. R., PIRZIO-BIROLI G., VIRANUVATTI V., FINCH C. A. The use of chromium as red-cell tag. Br J Haematol. 1955 Jul;1(3):249–263. doi: 10.1111/j.1365-2141.1955.tb05508.x. [DOI] [PubMed] [Google Scholar]
  11. ERSLEV A. J. Erythropoietic factor in the control of red cell production. Ann N Y Acad Sci. 1959 Jun 25;77:627–637. doi: 10.1111/j.1749-6632.1959.tb36930.x. [DOI] [PubMed] [Google Scholar]
  12. Edwards M. J., Martin R. J. Mixing technique for the oxygen-hemoglobin equilibrium and Bohr effect. J Appl Physiol. 1966 Nov;21(6):1898–1902. doi: 10.1152/jappl.1966.21.6.1898. [DOI] [PubMed] [Google Scholar]
  13. FILMANOWICZ E., GURNEY C. W. Studies on erythropoiesis. XVI. Response to a single dose of erythropoietin in polycythemic mouse. J Lab Clin Med. 1961 Jan;57:65–72. [PubMed] [Google Scholar]
  14. FREEDMAN B. J., PENINGTON D. G. ERYTHROCYTOSIS IN EMPHYSEMA. Br J Haematol. 1963 Oct;9:425–430. doi: 10.1111/j.1365-2141.1963.tb05465.x. [DOI] [PubMed] [Google Scholar]
  15. GIBLETT E. R., COLEMAN D. H., PIRZIOBIROLI G., DONOHUE D. M., MOTULSKY A. G., FINCH C. A. Erythrokinetics: quantitative measurements of red cell production and destruction in normal subjects and patients with anemia. Blood. 1956 Apr;11(4):291–309. [PubMed] [Google Scholar]
  16. GORDON A. S., WINKERT J., DORNFEST B. S., SIEGEL C. D. Studies on the actions and properties of the circulating erythropoietic stimulating factor. Ann N Y Acad Sci. 1959 Jun 25;77:650–676. doi: 10.1111/j.1749-6632.1959.tb36932.x. [DOI] [PubMed] [Google Scholar]
  17. Gordon A. S., Cooper G. W., Zanjani E. D. The kidney and erythropoiesis. Semin Hematol. 1967 Oct;4(4):337–358. [PubMed] [Google Scholar]
  18. HELLEGERS A. E., SCHRUEFER J. J. Nomograms and empirical equations relating oxygen tension, percentage saturation, and pH in maternal and fetal blood. Am J Obstet Gynecol. 1961 Feb;81:377–384. doi: 10.1016/s0002-9378(16)36380-3. [DOI] [PubMed] [Google Scholar]
  19. HILPERT P., FLEISCHMANN R. G., KEMPE D., BARTELS H. THE BOHR EFFECT RELATED TO BLOOD AND ERYTHROCYTE PH. Am J Physiol. 1963 Aug;205:337–340. doi: 10.1152/ajplegacy.1963.205.2.337. [DOI] [PubMed] [Google Scholar]
  20. Hamilton H. B., Iuchi I., Miyaji T., Shibata S. Hemoglobin Hiroshima (beta-143 histidine--aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia. J Clin Invest. 1969 Mar;48(3):525–535. doi: 10.1172/JCI106010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. JONXIS J. H., VISSER H. K. Determination of low percentages of fetal hemoglobin in blood of normal children. AMA J Dis Child. 1956 Dec;92(6):588–591. doi: 10.1001/archpedi.1956.02060030582007. [DOI] [PubMed] [Google Scholar]
  22. Jones R. T., Osgood E. E., Brimhall B., Koler R. D. Hemoglobin Yakina. I. Clinical and biochemical studies. J Clin Invest. 1967 Nov;46(11):1840–1847. doi: 10.1172/JCI105674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Metcalfe J., Bartels H., Moll W. Gas exchange in the pregnant uterus. Physiol Rev. 1967 Oct;47(4):782–838. doi: 10.1152/physrev.1967.47.4.782. [DOI] [PubMed] [Google Scholar]
  24. Moore W. M., Battaglia F. C., Hellegers A. E. Whole blood oxygen affinities of women with various hemoglobinopathies. Am J Obstet Gynecol. 1967 Jan 1;97(1):63–66. doi: 10.1016/0002-9378(67)90593-5. [DOI] [PubMed] [Google Scholar]
  25. Novy M. J., Edwards M. J., Metcalfe J. Hemoglobin Yakina. II. High blood oxygen affinity associated with compensatory erythrocytosis and normal hemodynamics. J Clin Invest. 1967 Nov;46(11):1848–1854. doi: 10.1172/JCI105675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Parer J. T., Hoversland A. S., Metcalfe J. Some respiratory characteristics of the blood of the adult and young African pygmy goat. J Appl Physiol. 1967 Apr;22(4):756–759. doi: 10.1152/jappl.1967.22.4.756. [DOI] [PubMed] [Google Scholar]
  27. Parker J. T., Metcalfe J. Oxygen transport by blood in relation to body size. Nature. 1967 Aug 5;215(5101):653–654. doi: 10.1038/215653a0. [DOI] [PubMed] [Google Scholar]
  28. REISSMANN K. R., RUTH W. E., NOMURA T. A human hemoglobin with lowered oxygen affinity and impaired heme-heme interactions. J Clin Invest. 1961 Oct;40:1826–1833. doi: 10.1172/JCI104406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. ROBINSON A. R., ROBSON M., HARRISON A. P., ZUELZER W. W. A new technique for differentiation of hemoglobin. J Lab Clin Med. 1957 Nov;50(5):745–752. [PubMed] [Google Scholar]
  30. Reed C. S., Hampson R., Gordon S., Jones R. T., Novy M. J., Brimhall B., Edwards M. J., Koler R. D. Erythrocytosis secondary to increased oxygen affinity of a mutant hemoglobin, hemoglobin Kempsey. Blood. 1968 May;31(5):623–632. [PubMed] [Google Scholar]
  31. Severinghaus J. W. Blood gas calculator. J Appl Physiol. 1966 May;21(3):1108–1116. doi: 10.1152/jappl.1966.21.3.1108. [DOI] [PubMed] [Google Scholar]
  32. Stamatoyannopoulos G., Yoshida A., Adamson J., Heinenberg S. Hemoglobin Rainier (beta145 Tyrosine rarr Histidine): Alkali-Resistant Hemoglobin with Increased Oxygen Affinity. Science. 1968 Feb 16;159(3816):741–743. doi: 10.1126/science.159.3816.741. [DOI] [PubMed] [Google Scholar]
  33. Van Dyke D., Nohr M. L., Lawrence J. H. Erythropoietin in the urine of normal and erythropoietically abnormal human beings. Blood. 1966 Oct;28(4):535–543. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES