Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1970 Jan;49(1):5–14. doi: 10.1172/JCI106222

Disposal of plasma heme in normal man and patients with intravascular hemolysis

David A Sears 1
PMCID: PMC322438  PMID: 4188269

Abstract

The clearance of plasma protein-bound heme, its sites of removal, and the reutilization of hemeiron were studied by radioisotopic techniques in normal human subjects and in patients with intravascular hemolysis.

In normal subjects, injected heme-59Fe was bound immediately by albumin and the β1-globulin, hemopexin. Its clearance from the plasma was descr bed by a single exponential equation, and the half-life in plasma was 7-8 hr. Removal was largely by the liver. Iron reutilization began promptly, and half the injected heme-iron was incorporated into circulating red cells within one cell life-span.

In patients with intravascular hemolysis, hemopexin was depleted, and injected heme was bound solely to albumin. Plasma clearance was described by a double exponential equation of the form: y = Ae-k1t + Be-k2t. The half-lives of the two components averaged 3.9 and 22.2 hr, respectively. Removal was by the liver in at least some of the patients, and iron reutilization was variable, depending on the state of body iron stores. When hemopex'n was depleted in a normal subject by repeated heme injection, clearance mimicked that observed in the patients.

Full text

PDF

Images in this article

6Image
on p.6
9Image
on p.9

Selected References

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

  1. Andersen M. N., Mouritzen C. V., Gabrieli E. Mechanisms of plasma hemoglobin clearance after acute hemolysis: studies in open-heart surgical patients. Ann Surg. 1966 Apr;163(4):529–536. doi: 10.1097/00000658-196604000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barrett V., Berk P. D., Menken M., Berlin N. I. Bilirubin turnover studies in normal and pathologic states using bilirubin-14C. Ann Intern Med. 1968 Feb;68(2):355–377. doi: 10.7326/0003-4819-68-2-355. [DOI] [PubMed] [Google Scholar]
  3. Bunn H. F., Jandl J. H. Exchange of heme among hemoglobins and between hemoglobin and albumin. J Biol Chem. 1968 Feb 10;243(3):465–475. [PubMed] [Google Scholar]
  4. CROSBY W. H., FURTH F. W. A modification of the benzidine method for measurement of hemoglobin in plasma and urine. Blood. 1956 Apr;11(4):380–383. [PubMed] [Google Scholar]
  5. CROSBY W. H., MUNN J. I., FURTH F. W. Standardizing a method for clinical hemoglobinometry. U S Armed Forces Med J. 1954 May;5(5):693–703. [PubMed] [Google Scholar]
  6. CROSBY W. H. The metabolism of hemoglobin and bile pigment in hemolytic disease. Am J Med. 1955 Jan;18(1):112–122. doi: 10.1016/0002-9343(55)90208-4. [DOI] [PubMed] [Google Scholar]
  7. FAULSTICK D. A., LOWENSTEIN J., YIENGST M. J. Clearance kinetics of haptoglobin-hemoglobin complex in the human. Blood. 1962 Jul;20:65–71. [PubMed] [Google Scholar]
  8. GARBY L., NOYES W. D. Studies on hemoglobin metabolism. I. The kinetic properties of the plasma hemoglobin pool in normal man. J Clin Invest. 1959 Sep;38:1479–1483. doi: 10.1172/JCI103925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GARBY L., NOYES W. D. Studies on hemoglobin metabolism. II. Pathways of hemoglobin iron metabolism in normal man. J Clin Invest. 1959 Sep;38:1484–1486. doi: 10.1172/JCI103926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GARBY L., OBARA J. Organ uptake and plasma transportation kinetics of hemoglobin in rats. Blut. 1960 Jun;6:143–146. doi: 10.1007/BF01630019. [DOI] [PubMed] [Google Scholar]
  11. HANKS G. E., CASSELL M., RAY R. N., CHAPLIN H., Jr Further modification of the benzidine method for measurement of hemoglobin in plasma; definitionn of a new range of normal values. J Lab Clin Med. 1960 Sep;56:486–498. [PubMed] [Google Scholar]
  12. HEIDE K., HAUPT H., STOERIKO K., SCHULTZE H. E. ON THE HEME-BINDING CAPACITY OF HEMOPEXIN. Clin Chim Acta. 1964 Nov;10:460–469. doi: 10.1016/0009-8981(64)90176-7. [DOI] [PubMed] [Google Scholar]
  13. Hosain F., Marsaglia G., Finch C. A. Blood ferrokinetics in normal man. J Clin Invest. 1967 Jan;46(1):1–9. doi: 10.1172/JCI105501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. JANDL J. H., GREENBERG M. S., YONEMOTO R. H., CASTLE W. B. Clinical determination of the sites of red cell sequestration in hemolytic anemias. J Clin Invest. 1956 Aug;35(8):842–867. doi: 10.1172/JCI103338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. JANDL J. H., JONES A. R., CASTLE W. B. The destruction of red cells by antibodies in man. I. Observations of the sequestration and lysis of red cells altered by immune mechanisms. J Clin Invest. 1957 Oct;36(10):1428–1459. doi: 10.1172/JCI103542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. JONES N. C., GARDNER B., HELPS R. Observations on the binding of haemoglobin and haematin by serum proteins in the rabbit. rat and guinea pig. Biochem J. 1961 May;79:220–223. doi: 10.1042/bj0790220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Keene W. R., Jandl J. H. The sites of hemoglobin catabolism. Blood. 1965 Dec;26(6):705–719. [PubMed] [Google Scholar]
  18. LABBE R. F., NISHIDA G. A new method of hemin isolation. Biochim Biophys Acta. 1957 Nov;26(2):437–437. doi: 10.1016/0006-3002(57)90033-1. [DOI] [PubMed] [Google Scholar]
  19. LATHEM W., JENSEN W. N. The renal excretion of hemoglobin in sickle cell anemia, with observations on spontaneously occurring hemoglobinemia and methemalbuminemia. J Lab Clin Med. 1962 Jan;59:137–146. [PubMed] [Google Scholar]
  20. LATHEM W., WORLEY W. E. The distribution of extracorpuscular hemoglobin in circulating plasma. J Clin Invest. 1959 Mar;38(3):474–483. doi: 10.1172/JCI103823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. MULLER-EBERHARD U., CLEVE H. Immunoelectrophoretic studies of the beta1-haem-binding globulin (haemopexin) in hereditary haemolytic disorders. Nature. 1963 Feb 9;197:602–603. doi: 10.1038/197602a0. [DOI] [PubMed] [Google Scholar]
  22. MURRAY R. K., CONNELL G. E., PERT J. H. The role of haptoglobin in the clearance and distribution of extracorpuscular hemoglobin. Blood. 1961 Jan;17:45–53. [PubMed] [Google Scholar]
  23. Muller-Eberhard U., Javid J., Liem H. H., Hanstein A., Hanna M. Plasma concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases. Blood. 1968 Nov;32(5):811–815. [PubMed] [Google Scholar]
  24. Muller-Eberhard U., Liem H. H., Hanstein A., Saarinen P. A. Studies on the disposal of intravascular heme in the rabbit. J Lab Clin Med. 1969 Feb;73(2):210–218. [PubMed] [Google Scholar]
  25. NOYES W. D., BOTHWELL T. H., FINCH C. A. The role of the reticulo-endothelial cell in iron metabolism. Br J Haematol. 1960 Jan;6:43–55. doi: 10.1111/j.1365-2141.1960.tb06216.x. [DOI] [PubMed] [Google Scholar]
  26. ODELL G. B. The dissociation of bilirubin from albumin and its clinical implications. J Pediatr. 1959 Sep;55:268–279. doi: 10.1016/s0022-3476(59)80223-7. [DOI] [PubMed] [Google Scholar]
  27. Rabiner S. F., Helbert J. R., Lopas H., Friedman L. H. Evaluation of a stroma-free hemoglobin solution for use as a plasma expander. J Exp Med. 1967 Dec 1;126(6):1127–1142. doi: 10.1084/jem.126.6.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. SEARS D. A., CROSBY W. H. INTRAVSCULAR HEMOLYSIS DUE TO INTRACARDIAC PROSTHETIC DEVICES: DIURNAL VARIATIONS RELATED TO ACTIVITY. Am J Med. 1965 Aug;39:341–354. doi: 10.1016/0002-9343(65)90060-4. [DOI] [PubMed] [Google Scholar]
  29. SNYDER A. L., SCHMID R. THE CONVERSION OF HEMATIN TO BILE PIGMENT IN THE RAT. J Lab Clin Med. 1965 May;65:817–824. [PubMed] [Google Scholar]
  30. Sears D. A., Anderson P. R., Foy A. L., Williams H. L., Crosby W. H. Urinary iron excretion and renal metabolism of hemoglobin in hemolytic diseases. Blood. 1966 Nov;28(5):708–725. [PubMed] [Google Scholar]
  31. Sears D. A. Depletion of plasma hemopexin in man by hematin injections. Proc Soc Exp Biol Med. 1969 Jun;131(2):371–373. doi: 10.3181/00379727-131-33880. [DOI] [PubMed] [Google Scholar]
  32. Sears D. A., Huser H. J. Plasma hematin-binding and clearance in the rhesus monkey. Proc Soc Exp Biol Med. 1966 Jan;121(1):111–116. doi: 10.3181/00379727-121-30712. [DOI] [PubMed] [Google Scholar]
  33. Sears D. A. Plasma heme-binding in patients with hemolytic disorders. J Lab Clin Med. 1968 Mar;71(3):484–494. [PubMed] [Google Scholar]
  34. YOUNG D. S., HICKS J. M. METHOD FOR THE AUTOMATIC DETERMINATION OF SERUM IRON. J Clin Pathol. 1965 Jan;18:98–102. doi: 10.1136/jcp.18.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES