P14: Degradation of High Molecular Weight Multimers of von Willebrand Factor under Whole Blood Conditions in High Turbulent Flow: Implications for Continuous Flow Left Ventricular Assist Devices

Abstract

Background: High turbulent flow often found in continuous flow left ventricular assist devices (cf-LVADs) is believed to cause acquired von Willebrand Syndrome (AvWS). Our group recently published a study on the kinetic and dynamic effects of various flows on the loss of high molecular weight multimers (HMWMs) of von Willebrand factor (vWF). In the study, we applied high shear to citrated human platelet-poor plasma (PPP) and characterized the flow by Reynolds number (Re). The present study aims to extend upon our previous findings by investigating the degradation of HMWM under whole blood conditions at higher flow conditions to be characterized by energy dissipation rate and clinically relevant exposure times previously employed. Methods: Diluted ovine blood with a hematocrit of 25%, dynamic viscosity of 3.0 cP and density of 1030 kg/m3 was flowed through a custom high shear rotary device. The device is designed to provide a fully controlled exposure time, texp and flow regime. The flow rate was set at 1.75 ml/sec, 0.76 ml/sec, or 0.38 ml/sec, resulting in an exposure time of 22 ms, 50 ms, or 100 ms, respectively. The dynamic flow condition was controlled by the speed of the rotor, ω, and characterized by the energy dissipation rate per unit mass, ε. The ω of 10k, 12k, 15k, 18k, 20k, and 22k RPM were applied, and the corresponding ε were estimated by running a series of large eddy simulations (LES). After each run, a 0.5 ml sample solution was collected, frozen in dry ice immediately, and shipped to the Blood Center of Wisconsin for multimer analysis. The amount of multimer degradation at each testing condition was assessed with respect to the mean of the initial concentration of HMWM of vWF in the controls. Results: The results show that the loss of HMWM at all given exposure times increases in a logarithmic manner within the extended flow conditions (Fig. 1A). The loss of HMWM versus energy dissipation rate at given texp is shown in Fig. 1B. It is noted that as the flow becomes more chaotic, the loss of HMWM appears to be primarily dominated by the energy dissipation rate while the exposure time to chaotic flow becomes less significant. It is not clear if the less significant effect of kinetics at relatively high flow conditions (>18k RPM) is because there are no more HMWM left to be cleaved by ADAMTS13, an enzyme that cleaves vWF. The results are consistent with our previous observations using human PPP, in that both flow conditions and exposure time play crucial roles in the destruction of HMWM. Conclusion: This study demonstrated the relative roles of flow and exposure time using whole blood to characterize the loss of HMWM in terms of energy dissipation rate and exposure time. The findings have the potential to assist in the design and optimization of blood pumps, ultimately leading to improved clinical outcomes for patients with AvWS.