Oxygen-dependent flow of sickle trait blood as an in vitro therapeutic benchmark for sickle cell disease treatments

American Journal of Hematology
Xinran LuDavid K Wood

Abstract

Although homozygous sickle cell disease is often clinically severe, the corresponding heterozygous state, sickle cell trait, is almost completely benign despite the fact that there is only a modest difference in sickle hemoglobin levels between the two conditions. In both conditions, hypoxia can lead to polymerization of sickle hemoglobin, changes in red cell mechanical properties, and impaired blood flow. Here, we test the hypothesis that differences in the oxygen-dependent rheological properties in the two conditions might help explain the difference in clinical phenotypes. We use a microfluidic platform that permits quantification of blood rheology under defined oxygen conditions in physiologically sized microchannels and under physiologic shear rates. We find that, even with its lower sickle hemoglobin concentration, sickle trait blood apparent viscosity increases with decreasing oxygen tension and may stop flowing under completely anoxic conditions, though far less readily than the homozygous condition. Sickle cell trait blood flow becomes impaired at significantly lower oxygen tension than sickle cell disease. We also demonstrate how sickle cell trait can serve as a benchmark for sickle cell disease therapies. We characte...Continue Reading

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Citations

Jan 1, 2020·British Journal of Haematology·Scott HansenJohn M Higgins
Jan 25, 2020·Annual Review of Pathology·Brody H FoyJohn M Higgins
Jun 13, 2020·Proceedings of the National Academy of Sciences of the United States of America·Eric R HenryWilliam A Eaton
Jan 5, 2021·Current Sports Medicine Reports·Francis G O'ConnorPatricia A Deuster
Sep 9, 2021·Blood Advances·Namita KumariSergei Nekhai

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