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Research Article Free access | 10.1172/JCI105863

Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia

John F. Bertles and Paul F. A. Milner

Hematology Unit, Department of Medicine, St. Luke's Hospital Center, New York 10025

Department of Pathology, University of the West Indies, Kingston, Jamaica

Find articles by Bertles, J. in: PubMed | Google Scholar

Hematology Unit, Department of Medicine, St. Luke's Hospital Center, New York 10025

Department of Pathology, University of the West Indies, Kingston, Jamaica

Find articles by Milner, P. in: PubMed | Google Scholar

Published August 1, 1968 - More info

Published in Volume 47, Issue 8 on August 1, 1968
J Clin Invest. 1968;47(8):1731–1741. https://doi.org/10.1172/JCI105863.
© 1968 The American Society for Clinical Investigation
Published August 1, 1968 - Version history
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Abstract

The amount of fetal hemoglobin (Hb F) in erythrocytes of patients with sickle cell anemia (Hb SS disease) was measured by two methods: (a) photometry of individual cells stained for Hb F by the Kleihauer-Betke technique; and (b) chemical assay of alkali-resistant hemoglobin in cells distributed according to specific gravity by ultracentrifugation. Irreversibly sickled cells (ISC), which could be identified directly during photometry and which were found to gather in high concentration at the bottom of ultracentrifuged cell columns, contained significantly less Hb F than non-ISC. Cell content of total Hb was constant regardless of cell size, shape, or ultracentrifugal behavior: thus absolute amounts of Hb F and S varied reciprocally from cell to cell.

In experiments designed to estimate age, at formation, and rate of destruction of ISC, Hb SS blood was incubated with selenomethionine-75Se (which labels reticulocytes) or 51Cr (which labels erythrocytes at random) and reinfused. Sequential blood samples were separated by ultracentrifugation into fractions rich in reticulocytes, non-ISC, and ISC; and chronological changes in the specific activity of each fraction were determined. Analogous information was obtained from radioautography of sequential blood samples after reinfusion of whole blood labeled with amino acids-3H: this technique permitted direct visual characterization of labeled erythrocytes as ISC or non-ISC, all of which had been reticulocytes at the time of reinfusion. The transformation of non-ISC into ISC, presumably a manifestation of membrane damage, proved to begin soon after cell release from the marrow; and ISC subsequently underwent rapid removal from the circulating blood.

It is therefore apparent from these studies that, in Hb SS disease, relatively small reciprocal changes in the amounts of the two major hemoglobins carry predictive importance: (a) net synthesis of Hb F is least in erythroid cells destined to become ISC; and (b) these irreversibly deformed erythrocytes suffer preferential destruction.

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