A biophysical marker of severity in sickle cell disease
Author(s)Mahadevan, L.; Wood, David K.; Bhatia, Sangeeta N.; Soriano, Alicia; HIggins, John M.
A Biophysical Indicator of Vaso-occlusive Risk in Sickle Cell Disease
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The search for predictive indicators of disease has largely focused on molecular markers. However, biophysical markers, which can integrate multiple pathways, may provide a more global picture of pathophysiology. Sickle cell disease affects millions of people worldwide and has been studied intensely at the molecular, cellular, tissue, and organismal level for a century, but there are still few, if any, markers quantifying the severity of this disease. Because the complications of sickle cell disease are largely due to vaso-occlusive events, we hypothesized that a physical metric characterizing the vaso-occlusive process could serve as an indicator of disease severity. Here, we use a microfluidic device to characterize the dynamics of “jamming,” or vaso-occlusion, in physiologically relevant conditions, by measuring a biophysical parameter that quantifies the rate of change of the resistance to flow after a sudden deoxygenation event. Our studies show that this single biophysical parameter could be used to distinguish patients with poor outcomes from those with good outcomes, unlike existing laboratory tests. This biophysical indicator could therefore be used to guide the timing of clinical interventions, to monitor the progression of the disease, and to measure the efficacy of drugs, transfusion, and novel small molecules in an ex vivo setting.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Science Translational Medicine
American Association for the Advancement of Science (AAAS)
Wood, D. K., A. Soriano, L. Mahadevan, J. M. Higgins, and S. N. Bhatia. “A Biophysical Indicator of Vaso-Occlusive Risk in Sickle Cell Disease.” Science Translational Medicine 4, no. 123 (February 29, 2012): 123ra26–123ra26.
Author's final manuscript