{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:38:00Z","timestamp":1785332280836,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T00:00:00Z","timestamp":1540771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Artificial Organs"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the prevailing use of the continuous flow left ventricular assist devices (cf\u2010LVAD), acquired von Willebrand syndrome (AvWS) associated with cf\u2010LVAD still remains a major complication. As AvWS is known to be dependent on shear stress (<jats:italic>\u03c4<\/jats:italic>) and exposure time (<jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>), this study examined the degradation of high molecular weight multimers (HMWM) of von Willebrand factor (vWF) in terms of <jats:italic>\u03c4<\/jats:italic> and <jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>. Two custom apparatus, i.e., capillary\u2010tubing\u2010type degrader (CTD) and Taylor\u2010Couette\u2010type degrader (TCD) were developed for short\u2010term (0.033 sec\u00a0\u2264\u00a0<jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>\u00a0\u2264\u00a01.05\u00a0s) and long\u2010term (10\u00a0s\u00a0\u2264\u00a0<jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>\u00a0\u2264\u00a010\u00a0min) shear exposures of vWF, respectively. Flow conditions indexed by Reynolds number (Re) for CTD were 14\u00a0\u2264\u00a0Re\u00a0\u2264\u00a0288 with corresponding laminar stress level of 52\u00a0\u2264\u00a0<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aor13323-math-0001.png\" xlink:title=\"urn:x-wiley:0160564X:media:aor13323:aor13323-math-0001\"\/>\u00a0\u2264\u00a01042\u00a0dyne\/cm<jats:sup>2<\/jats:sup>. Flow conditions for TCD were 100\u00a0\u2264\u00a0Re\u00a0\u2264\u00a02500 with corresponding rotor speed of 180\u00a0\u2264\u00a0<jats:italic><jats:sub>o<\/jats:sub><\/jats:italic>\u00a0\u2264\u00a04000\u00a0RPM and laminar stress level of 50\u00a0\u2264\u00a0<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aor13323-math-0002.png\" xlink:title=\"urn:x-wiley:0160564X:media:aor13323:aor13323-math-0002\"\/>\u00a0\u2264\u00a01114\u00a0dyne\/cm<jats:sup>2<\/jats:sup>. Due to transitional and turbulent flows in TCD at Re\u00a0&gt;\u00a01117, total stress (i.e.,<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aor13323-math-0003.png\" xlink:title=\"urn:x-wiley:0160564X:media:aor13323:aor13323-math-0003\"\/>\u00a0=\u00a0laminar\u00a0+\u00a0turbulent) 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\u00a0mM and 10\u00a0mM) 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\u00a0&lt;\u00a01117 (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aor13323-math-0004.png\" xlink:title=\"urn:x-wiley:0160564X:media:aor13323:aor13323-math-0004\"\/>\u00a0=\u00a01012\u00a0dyne\/cm<jats:sup>2<\/jats:sup>), increase in degradation of HMWM was observed beyond Re of 1117 for all given exposure times. At Re ~ 2500 (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aor13323-math-0005.png\" xlink:title=\"urn:x-wiley:0160564X:media:aor13323:aor13323-math-0005\"\/>\u00a0=\u00a03070\u00a0dyne\/cm<jats:sup>2<\/jats:sup>) with <jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>\u00a0=\u00a060\u00a0s, a severe degradation of HMWM (90.7\u00a0\u00b1\u00a03.8%, abnormal) was observed, and almost complete degradation of HMWM (96.1\u00a0\u00b1\u00a01.9%, abnormal) was observed with <jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>\u00a0=\u00a0600\u00a0s. The inhibition studies with 5\u00a0mM EDTA at Re ~ 2500 showed that loss of HMWM was negligible (&lt;10%, normal) for all given exposure times except for <jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>\u00a0=\u00a010\u00a0min (39.5\u00a0\u00b1\u00a022.3%, borderline\u2010abnormal). With 10\u00a0mM EDTA, no degradation of HMWM was observed (11.1\u00a0\u00b1\u00a04.4%, normal) even for <jats:italic>t<\/jats:italic><jats:sub>exp<\/jats:sub>\u00a0=\u00a010\u00a0min. This study investigated the effect of shear stress and exposure time on the HMWM of vWF in laminar and turbulent flows. The inhibition study by EDTA confirms that degradation of HMWM is initiated by shear\u2010induced unfolding followed by enzymatic cleavage at given conditions. Determination of magnitude of each mechanism needs further investigation. It is also important to note that the degradation of vWF is highly dependent on turbulence regardless of the time exposed within our testing conditions.<\/jats:p>","DOI":"10.1111\/aor.13323","type":"journal-article","created":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T10:57:53Z","timestamp":1540897073000},"page":"199-206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Stress and Exposure Time on von Willebrand Factor Degradation"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2980-3504","authenticated-orcid":false,"given":"Choon\u2010Sik","family":"Jhun","sequence":"first","affiliation":[{"name":"Division of Applied Biomedical Engineering, Department of Surgery Penn State College of Medicine  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Siedlecki","sequence":"additional","affiliation":[{"name":"Division of Applied Biomedical Engineering, Department of Surgery Penn State College of Medicine  Hershey PA USA"},{"name":"Department of Biomedical Engineering Penn State University  University Park PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichong","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Applied Biomedical Engineering, Department of Surgery Penn State College of Medicine  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Lukic","sequence":"additional","affiliation":[{"name":"Division of Applied Biomedical Engineering, Department of Surgery Penn State College of Medicine  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Newswanger","sequence":"additional","affiliation":[{"name":"Division of Applied Biomedical Engineering, Department of Surgery Penn State College of Medicine  Hershey PA 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