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Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients

In sickle cell disease (SCD), sickle hemoglobin (HbS) polymerizes upon deoxygenation, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso‐occlusive crises and chronic hemolytic anemia. To date, there are no reliable laboratory para...

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Autores principales: Rab, Minke A.E., van Oirschot, Brigitte A., Bos, Jennifer, Merkx, Tesy H., van Wesel, Annet C.W., Abdulmalik, Osheiza, Safo, Martin K., Versluijs, Birgitta A., Houwing, Maite E., Cnossen, Marjon H., Riedl, Jurgen, Schutgens, Roger E.G., Pasterkamp, Gerard, Bartels, Marije, van Beers, Eduard J., van Wijk, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518936/
https://www.ncbi.nlm.nih.gov/pubmed/30784099
http://dx.doi.org/10.1002/ajh.25443
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author Rab, Minke A.E.
van Oirschot, Brigitte A.
Bos, Jennifer
Merkx, Tesy H.
van Wesel, Annet C.W.
Abdulmalik, Osheiza
Safo, Martin K.
Versluijs, Birgitta A.
Houwing, Maite E.
Cnossen, Marjon H.
Riedl, Jurgen
Schutgens, Roger E.G.
Pasterkamp, Gerard
Bartels, Marije
van Beers, Eduard J.
van Wijk, Richard
author_facet Rab, Minke A.E.
van Oirschot, Brigitte A.
Bos, Jennifer
Merkx, Tesy H.
van Wesel, Annet C.W.
Abdulmalik, Osheiza
Safo, Martin K.
Versluijs, Birgitta A.
Houwing, Maite E.
Cnossen, Marjon H.
Riedl, Jurgen
Schutgens, Roger E.G.
Pasterkamp, Gerard
Bartels, Marije
van Beers, Eduard J.
van Wijk, Richard
author_sort Rab, Minke A.E.
collection PubMed
description In sickle cell disease (SCD), sickle hemoglobin (HbS) polymerizes upon deoxygenation, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso‐occlusive crises and chronic hemolytic anemia. To date, there are no reliable laboratory parameters or assays capable of predicting disease severity or monitoring treatment effects. We here report on the oxygenscan, a newly developed method to measure RBC deformability (expressed as Elongation Index ‐ EI) as a function of pO(2). Upon a standardized, 22 minute, automated cycle of deoxygenation (pO(2) median 16 mmHg ± 0.17) and reoxygenation, a number of clinically relevant parameters are produced in a highly reproducible manner (coefficients of variation <5%). In particular, physiological modulators of oxygen affinity, such as, pH and 2,3‐diphosphoglycerate showed a significant correlation (respectively R = ‑0.993 and R = 0.980) with Point of Sickling (PoS(5%)), which is defined as the pO(2) where a 5% decrease in EI is observed during deoxygenation. Furthermore, in vitro treatment with antisickling agents, including GBT440, which alter the oxygen affinity of hemoglobin, caused a reproducible left‐shift of the PoS, indicating improved deformability at lower oxygen tensions. When RBCs from 21 SCD patients were analyzed, we observed a significantly higher PoS in untreated homozygous SCD patients compared to treated patients and other genotypes. We conclude that the oxygenscan is a state‐of‐the‐art technique that allows for rapid analysis of sickling behavior in SCD patients. The method is promising for personalized treatment, development of new treatment strategies and could have potential in prediction of complications.
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spelling pubmed-65189362019-05-21 Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients Rab, Minke A.E. van Oirschot, Brigitte A. Bos, Jennifer Merkx, Tesy H. van Wesel, Annet C.W. Abdulmalik, Osheiza Safo, Martin K. Versluijs, Birgitta A. Houwing, Maite E. Cnossen, Marjon H. Riedl, Jurgen Schutgens, Roger E.G. Pasterkamp, Gerard Bartels, Marije van Beers, Eduard J. van Wijk, Richard Am J Hematol Research Articles In sickle cell disease (SCD), sickle hemoglobin (HbS) polymerizes upon deoxygenation, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso‐occlusive crises and chronic hemolytic anemia. To date, there are no reliable laboratory parameters or assays capable of predicting disease severity or monitoring treatment effects. We here report on the oxygenscan, a newly developed method to measure RBC deformability (expressed as Elongation Index ‐ EI) as a function of pO(2). Upon a standardized, 22 minute, automated cycle of deoxygenation (pO(2) median 16 mmHg ± 0.17) and reoxygenation, a number of clinically relevant parameters are produced in a highly reproducible manner (coefficients of variation <5%). In particular, physiological modulators of oxygen affinity, such as, pH and 2,3‐diphosphoglycerate showed a significant correlation (respectively R = ‑0.993 and R = 0.980) with Point of Sickling (PoS(5%)), which is defined as the pO(2) where a 5% decrease in EI is observed during deoxygenation. Furthermore, in vitro treatment with antisickling agents, including GBT440, which alter the oxygen affinity of hemoglobin, caused a reproducible left‐shift of the PoS, indicating improved deformability at lower oxygen tensions. When RBCs from 21 SCD patients were analyzed, we observed a significantly higher PoS in untreated homozygous SCD patients compared to treated patients and other genotypes. We conclude that the oxygenscan is a state‐of‐the‐art technique that allows for rapid analysis of sickling behavior in SCD patients. The method is promising for personalized treatment, development of new treatment strategies and could have potential in prediction of complications. John Wiley & Sons, Inc. 2019-03-08 2019-05 /pmc/articles/PMC6518936/ /pubmed/30784099 http://dx.doi.org/10.1002/ajh.25443 Text en © 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Rab, Minke A.E.
van Oirschot, Brigitte A.
Bos, Jennifer
Merkx, Tesy H.
van Wesel, Annet C.W.
Abdulmalik, Osheiza
Safo, Martin K.
Versluijs, Birgitta A.
Houwing, Maite E.
Cnossen, Marjon H.
Riedl, Jurgen
Schutgens, Roger E.G.
Pasterkamp, Gerard
Bartels, Marije
van Beers, Eduard J.
van Wijk, Richard
Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients
title Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients
title_full Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients
title_fullStr Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients
title_full_unstemmed Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients
title_short Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients
title_sort rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518936/
https://www.ncbi.nlm.nih.gov/pubmed/30784099
http://dx.doi.org/10.1002/ajh.25443
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