Turbulent flow mediates VWF cleavage in the presence of ADAMTS13, decreasing the ability of VWF to sustain platelet adhesion.

Figure 1. Vane and Cup Rheological Setup. Top view of the vane setup (upper left), which consists of a four-blade vane rotor that is lowered into a stainless steel cup (internal radius of 13.6 mm) until a 1 mm axial gap between the vane and the bottom of the cup is achieved. Side view of the vane rotor (upper right), which consists of four blades with a 1 mm thickness. The graph (bottom) shows measured torque as a function of input rotational rate, showing the determination of laminar, transitional, and turbulent flow regimes.

Acquired von Willebrand syndrome is defined by excessive cleavage of the von Willebrand Factor (VWF) and is associated with impaired primary hemostasis and severe bleeding in patients with severe aortic stenosis an in patients undergoing procedures during extracorporeal circulation. It often develops when blood is exposed to nonphysiological flow such as in aortic stenosis or mechanical circulatory support. In collaboration with David Bark’s laboratory, we recently evaluated the role of laminar, transitional, and turbulent flow on VWF cleavage and the effects on VWF function. By using a vane rheometer to generate laminar, transitional, and turbulent flow we evaluated the effect of these flows on VWF cleavage in the presence of its main protease ADAMTS13 (figure 1). Computational fluid dynamics was used to estimate the flow fields and forces within the vane rheometer under each flow condition. We showed that turbulent flow is required for excessive cleavage of VWF in an ADAMTS13-dependent manner in reconstituted systems and whole blood. Importantly, our computational fluid dynamics results showed that under turbulent conditions, the Kolmogorov scale approaches the size of VWF (figure 2). Finally cleavage of VWF in these conditions had functional consequences under flow as the resulting VWF had decreased ability to bind platelets and collagen (figure 3). We continue these studies and we hope that these findings will impact the design of mechanical circulatory support devices.

Figure 2. Computational fluid dynamics results showing 3D particle pathlines and velocity magnitude contours on the middle plane for the different rotating speeds. Left-to-right: 10 rad/s, 100 rad/s and 450 rad/s
Figure 3. Western blot (top row) and multimer analysis (bottom row). Results comparing cleavage under laminar, transitional and turbulent flow.