{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:10:35Z","timestamp":1791141035132,"version":"4.1.0"},"reference-count":42,"publisher":"Georg Thieme Verlag KG","issue":"11","funder":[{"name":"Lille-II University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Haemorrhagic episodes in patients carrying circulatory assist devices represent a severe life-threatening clinical complication. These bleeding episodes may originate from a reduced functionality of von Willebrand factor (VWF), a multimeric protein pertinent to the formation of a haemostatic plug. It has been reported that the reduced functionality is due to increased proteolytic degradation by the enzyme ADAMTS13, a phenomenon that is facilitated by device-induced increases in shear stress to which VWF is exposed. Here, we have tested a series of VWF-derived protein fragments and monoclonal murine anti-VWF antibodies for their capacity to reduce shear stress-dependent degradation of VWF. Via direct binding experiments, we identified an anti-VWF antibody that partially blocked VWF-ADAMTS13 interactions (46 \u00b1 14%). Epitope mapping experiments revealed that the antibody, designated mAb508, is directed against the distal portion of the VWF D4-domain (residues 2134\u20132301) and recognises a synthetic peptide encompassing residues 2158\u20132169. Consistent with its partial inhibition of VWF-ADAMTS13 interactions in binding assays, mAb508 reduced ADAMTS13-mediated VWF degradation in a vortex-based degradation assay by 48 \u00b1 10%. In a HeartMateII-based whole bloodperfusion system, mAb508 was able to reduce degradation of highmolecular- weight (HMW)-VWF-multimers dose-dependently, with a maximal inhibition (83 \u00b1 8%) being reached at concentrations of 10 \u03bcg\/ml or higher. In conclusion, we report that partial inhibition of VWF-ADAMTS13 interactions using an anti-VWF antibody can prevent excessive degradation of HMW-VWF multimers. This strategy may be used for the development of therapeutic options to treat bleeding episodes due to shear stress-dependent VWF degradation, for instance in patients carrying circulatory assist devices.<\/jats:p>","DOI":"10.1160\/th14-02-0148","type":"journal-article","created":{"date-parts":[[2014,7,17]],"date-time":"2014-07-17T07:34:14Z","timestamp":1405582454000},"page":"1014-1023","source":"Crossref","is-referenced-by-count":47,"title":["Antibody-based prevention of von Willebrand factor degradation mediated by circulatory assist 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