Mathematical modelling and in vitro studies of high shear blood clot formation in a microfluidic system*

Arterial blood clot formation (thrombosis) is the leading cause of both stroke and heart attack. Accurate prediction of clotting dynamics under high shear is a key part of developing safe and effective treatments. We use in vitro and mathematical modelling to examine high shear thrombosis in a microfluidic system. Thrombosis under pathologically high shear stresses relies on the protein Von Willebrand Factor (VWF). At high shear VWF unfolds, which exposes binding sites, and facilitates rapid platelet deposition and clot formation.

In vitro, platelets and VWF flow over collagen in a rectangular stenosis model. Platelet deposition over time is measured for a range of flow rates. The in vitro data is used to parameterise a continuum mathematical model which examines the early stages of thrombosis. The model includes a novel mechanistic description of VWF dynamics using a dilute limit of a viscoelastic fluid model. We exploit the small aspect ratio of the microfluidic system to construct a reduced model. The reduced model is used to investigate the effect of varying stenosis geometry and blood flow conditions on the unfolding of VWF and subsequent platelet binding. This allows for effective prediction of the location and timescale platelet deposition for a given stenosis.