Stress and Exposure Time on von Willebrand Factor Degradation

Despite the prevailing use of the continuous flow left ventricular assist devices (cf‐LVAD), acquired von Willebrand syndrome (AvWS) associated with cf‐LVAD still remains a major complication. As AvWS is known to be dependent on shear stress (τ) and exposure time (texp), this study examined the degradation of high molecular weight multimers (HMWM) of von Willebrand factor (vWF) in terms of τ and texp. Two custom apparatus, i.e., capillary‐tubing‐type degrader (CTD) and Taylor‐Couette‐type degrader (TCD) were developed for short‐term (0.033 sec ≤ texp ≤ 1.05 s) and long‐term (10 s ≤ texp ≤ 10 min) shear exposures of vWF, respectively. Flow conditions indexed by Reynolds number (Re) for CTD were 14 ≤ Re ≤ 288 with corresponding laminar stress level of 52 ≤ τCTD ≤ 1042 dyne/cm2. Flow conditions for TCD were 100 ≤ Re ≤ 2500 with corresponding rotor speed of 180 ≤ o ≤ 4000 RPM and laminar stress level of 50 ≤ τTCD ≤ 1114 dyne/cm2. Due to transitional and turbulent flows in TCD at Re > 1117, total stress (i.e.,τtotal = laminar + turbulent) was also calculated using a computational fluid dynamics (CFD) solver, Converge CFD (Converge Science Inc., Madison, WI, USA). Inhibition of ADAMTS13 with different concentration of EDTA (5 mM and 10 mM) was also performed to investigate the mechanism of cleavage in terms of mechanical and enzymatic aspects. Degradation of HMWM with CTD was negligible at all given testing conditions. Although no degradation of HMWM was observed with TCD at Re