Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 34; pp. 9527 - 9532
• Main Authors: Hosseini, Poorya, Abidi, Sabia Z., Du, E, Papageorgiou, Dimitrios P., Choi, Youngwoon, Park, YongKeun, Higgins, John M., Kato, Gregory J., Suresh, Subra, Dao, Ming, Yaqoob, Zahid, So, Peter T. C.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 23.08.2016
• Subjects: Anemia, Sickle Cell - blood; Anemia, Sickle Cell - drug therapy; Anemia, Sickle Cell - pathology; Antisickling Agents - pharmacology; Biological Sciences; Biomarkers; Biomarkers - blood; Biophysics; Blood Cell Count; Blood Transfusion; Erythrocyte Deformability; Erythrocytes - drug effects; Erythrocytes - metabolism; Erythrocytes - pathology; Fetal Hemoglobin; Humans; Hydroxyurea - pharmacology; Hypoxia; Interferometry; Microscopy, Interference; Oxygen - pharmacology; Physical Sciences; Prescription drugs; Sickle cell disease; cell volume; cellular properties; biomarkers; cell deformability; sickle cell anemia
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1610435113

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.