Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia
Open accessAbstract
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-(75)Se (which labels reticulocytes) or (51)Cr (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-(3)H: 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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Improved F-cell survival is likely a result of HbF protecting the cell from HbS polymer-induced damage.
“Improved F-cell survival is likely a result of HbF protecting the cell from HbS polymer-induced damage.[44][45][46][47]”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [44]
The Discussion reports preferential survival of Hb SS erythrocytes with higher Hb F and a short lifespan for irreversibly sickled cells. The Abstract describes irreversible sickling as a presumed manifestation of membrane damage, but the paper does not identify HbS polymer-induced damage as the mechanism that HbF prevents. (LLM, conf=0.84)
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Fetal hemoglobin in sickle cell anemia
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Fetal hemoglobin in sickle cell anemia
Steinberg, M. H. (2020) · Blood · doi:10.1182/blood.2020007645 · Cited by 136 · see citing works
Khandros, E., Huang, P., Peslak, S. A., Sharma, M., Abdulmalik, O., Giardine, B. M., Zhang, Z., Keller, C. A., Hardison, R. C., & Blobel, G. A. (2020) · Blood · doi:10.1182/blood.2020005058 · Cited by 40 · see citing works
- Authors
- Bertles, J. F., & Milner, P. F. A.
- Affiliations
- St. Luke's-Roosevelt Hospital Center (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1968-08-01
- Volume
- 47
- Issue
- 8
- Pages
- 1731-1741
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC297333
- OpenAlex
- W2143525427
- Semantic Scholar
- 49baec02d9ece419be5a640e67c3a4861013f39f
- Cited by
- 261
- References
- 24
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 5 · 2016: 5 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Whitehall Foundation
- Medical Research Council
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- sickle cell disease, fetal hemoglobin, hemoglobin S, erythrocyte deformability, reticulocytes, erythrocyte destruction, erythrocyte membrane damage, hemoglobin synthesis, erythrocyte age, autoradiography, chromium-51
- MeSH terms
- Adult, Amino Acids, Anemia, Sickle Cell, Child, Chromium Isotopes, Erythrocyte Aging, Erythrocytes, Abnormal, Female, Hemoglobins, Abnormal, Humans, Male, Methionine, Photometry, Radioisotopes, Selenium, Tritium, Ultracentrifugation
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