Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak corre...

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Bibliographic Details
Main Authors: Hosseini, Poorya, Abidi, Sabia Z., Du, E, Papageorgiou, Dimitrios P., Choi, Youngwoon, Higgins, John M., Kato, Gregory J., Suresh, Subra, Dao, Ming, Yaqoob, Zahid, So, Peter T. C., Park, YongKeun, Ph.D. Massachusetts Institute of Technology
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Published: National Academy of Sciences (U.S.) 2018
Online Access:http://hdl.handle.net/1721.1/114975
https://orcid.org/0000-0001-7347-7887
https://orcid.org/0000-0003-2678-4491
https://orcid.org/0000-0001-5372-385X
https://orcid.org/0000-0003-4698-6488
Description
Summary:Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.