PB1403 - Physiological Levels of Vascular Turbulence Increase Hemolysis with Implications for Vascular Dysfunction in Sickle Cell Disease

Background: Sickle Cell Disease (SCD) is a chronic and debilitating disease characterized by extensive hemolysis and an unpredictable course of vaso-occlusion, pain crises, and stroke. While SCD has been well described in the context of venous circulation; the root of arterial pathologies that arise in SCD, such as stroke, remains elusive. Previous studies have suggested that anemic conditions exhibit higher propensities for turbulence, a known contributor to endothelial disruption. Though no data exists for how much this affects sickle RBCs (sRBCs).

Aims: We will investigate the physiologic connection between circulatory turbulence and sRBCs by first, understanding the dynamic conditions that cause sRBC hemolysis so that we can begin to predict when and where it will occur in the vascular network and how to mitigate it. Second, we will characterize how turbulent sRBC suspensions impact the endothelium to provide more insight into the mechanisms of endothelial dysfunction observed in SCD.

Methods: Using a multi-well-plate vortex mixer paradigm, we expose small volumes of sRBC suspensions to turbulence with varied temporal and cellular conditions. Hemolysis levels are quantified using the absorbance measurements of free hemoglobin in the well following each condition. To assess the vascular response, flow cytometric quantification of expressed biomarkers of endothelial dysfunction is being used.

Results: Our data suggests a correlation between turbulence and hemolysis that occurs at a higher degree in sRBCs relative to control RBCs. We are investigating the morphological effects of such exposure on sRBCs as well as the endothelial response to turbulent sickle cell suspensions.

Conclusion(s): Here we demonstrate a simple tool for investigating hemodynamics and its connection to widespread vascular and thromboembolic pathologies in SCD. Extensive computational modeling and experimental validation of this benchtop system are ongoing. Our future work includes locating pathologic areas in circulation based on existing data to develop a predictive arterial map for sRBC hemolysis.