The Effects of Therapeutic Strategies in Restoring Sickle Cell Disease Blood Rheology

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The Effects of Therapeutic Strategies in Restoring Sickle Cell Disease Blood Rheology

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2022-04

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Sickle cell disease is a hereditary disease of the hemoglobin with devastating acute and chronic complications. The pathological polymerization of sickle hemoglobin during hypoxia reduces red blood cell deformability and increases blood viscosity. These biophysical changes to the red blood cells and whole blood rheology can obstruct blood flow and contribute to vaso-occlusion in the microcirculation. Though the genetic and molecular basis for the disease has been understood for decades, limited treatment options are available to those who suffer from this disease. Microfluidic platforms provide a physiologically relevant pre-clinical model to assess the response of sickle cell blood rheology to therapeutic strategies in vitro. This work focuses on the roles of affinity modifying compounds and high expression of fetal hemoglobin in inhibiting sickle hemoglobin polymerization and restoring healthy blood rheology. Isolating the biophysical effects of these therapeutic strategies on blood flow provides a better understanding of their mechanisms of action that may be of clinical significance. Microfluidic studies of sickle cell disease blood flow may help accelerate drug development and improve patient outcomes.

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University of Minnesota Ph.D. dissertation. April 2022. Major: Biomedical Engineering. Advisor: David Wood. 1 computer file (PDF); xi, 126 pages.

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Hansen, Scott. (2022). The Effects of Therapeutic Strategies in Restoring Sickle Cell Disease Blood Rheology. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/256990.

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