Collaborators: Wilbur Lam (Emory/GT), David Wood (UMN)
Funding Source: National Heart, Lung, and Blood Institute (NHLBI) R01
Sickle cell disease (SCD) is a genetic blood disorder caused by a homozygous mutation in the gene that codes for hemoglobin (Hb), the oxygen-carrying component of red blood cells (RBC). Blood with a high concentration of sickle hemoglobin (HbS) has markedly different rheological properties than normal blood, and these properties—viscosity in particular—are thought to contribute to the incidence of vaso-occlusion and its related symptoms in SCD patients. Current disease management guidelines recommend regular RBC transfusions to lower the proportion of HbS in the blood. These “one size fits all” transfusion protocols are based on only a few historical clinical studies and have not been re-evaluated to take into account current knowledge that multiple physical, chemical, and biological mechanisms—as well as their interactions—all contribute to the stoppage of blood flow.
In collaboration with Drs. David Wood and Wilbur Lam, we will expand on the capabilities of in vitro microfluidic models of vaso-occlusion previously developed by their research groups that have already proven to be valuable tools for quantifying blood rheology and occlusion characteristics. Transfusion protocols can be simulated in the device by mixing normal blood with sickled blood from SCD patients and monitoring the consequent flow dynamics. To handle the wealth of data generated by these experiments, we will leverage our expertise in analytics and predictive modeling to discover relationships between blood flow characteristics and patient-specific hematologic profiles. Based on these experiments and analyses, we expect to identify a more clinically relevant, quantitative definition for effective blood viscosity as a biomarker for vaso-occlusion and use this to inform evidence-based transfusion targets which result in the best outcomes for SCD patients.