Effect of Pulse Frequency on Shear-Induced Extension of Von Willebrand Factor in Continuous-Flow Ventricular Assist...

Patients with continuous-flow ventricular assist devices (CF-VADs) face an elevated risk of nonsurgical bleeding. One hypothetical cause is that the loss of pulsatility promotes unraveling and enzymatic degradation of von Willebrand factor (VWF), a key clotting protein. Artificial pulsatility has been proposed to counter this effect, but the role of pulse frequency in VWF unraveling remains unclear. This study investigates VWF conformational changes in response to varying pulse frequencies. Membrane-bound VWF on human aortic endothelial cells (HAECs) exposed to pulsatile in vitro conditions exhibited significantly less unraveling than under continuous flow ( p < 0.005). To enable real-time observation of VWF conformation, VWF was immobilized in a microfluidic device and exposed to continuous or pulsatile flows (20, 40, or 60 pulses/min) to model HAEC-bound unraveling. Results showed that frequencies greater than or equal to 40 pulses/min significantly reduced maximum extension compared with continuous flow and low-frequency conditions (≤ 20 pulses/min), whereas minimum extension was greatest under continuous flow and declined as frequency increased. Step-change flow experiments revealed a time constant of 0.19 ± 0.04 seconds for extension and ~1 second for recoiling. These findings support optimizing pulsatile flow frequency as a strategy to minimize VWF unfolding and mitigate nonsurgical bleeding in CF-VAD patients.