{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:00:54Z","timestamp":1761541254645},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T00:00:00Z","timestamp":1429747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"MURST","award":["60A07-4123\/11"],"award-info":[{"award-number":["60A07-4123\/11"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>This report concerns abnormal <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) and collagen interactions coinciding with the p.R1819_C1948delinsS von Willebrand factor (<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>) mutation associated with the deletion of the C\u2010terminus of the A3 domain (amino acids 1819\u20131947) in a patient with a history of bleeding. The von Willebrand disease (<jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>) phenotype of the patient featured low plasma and platelet <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>, multimers with smears extending over the highest normal oligomers in plasma, but not platelets, and an impaired collagen\u2010binding capacity. <jats:italic>In vitro<\/jats:italic> full\u2010length p.R1819_C1948delinsS <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> expression showed impaired <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> release, increased cellular content with normally\u2010multimerized <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> and impaired collagen binding. The recombinant p.R1819_C1948delinsS <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> fragment, extending from domains A2 to B3 (p.R1819_C1948delinsS A2\u2010B3 <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>), was completely resistant to proteolysis by <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>13 in the presence of 1\u00b75\u00a0mol\/l urea, unlike its normal counterpart. The defect stems from impaired <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>13 binding to p.R1819_C1948delinsS A2\u2010B3, analysed under static conditions. Partial deletion of the C\u2010terminus of the A3 domain thus makes <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> resistant to <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>13, interfering with <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>13 binding to <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>, and impairing the collagen\u2010binding capacity of <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>. The p.R1819_C1948delinsS mutation has both haemorrhagic features (defective collagen binding, reduced <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> levels) and prothrombotic (<jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>13 resistance) features, and the latter probably mitigate the patient's bleeding symptoms.<\/jats:p>","DOI":"10.1111\/bjh.13472","type":"journal-article","created":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T05:31:13Z","timestamp":1429767073000},"page":"564-573","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The p.R1819_C1948delinsS mutation makes von Willebrand factor ADAMTS13\u2010resistant and reduces its collagen\u2010binding capacity"],"prefix":"10.1111","volume":"170","author":[{"given":"Viviana","family":"Daidone","sequence":"first","affiliation":[{"name":"Thrombohaemorrhagic Disorders Unit Department of Medicine University of Padua 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margherita","family":"Morpurgo","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry and Pharmacology Department University of Padua Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Zanotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Padua Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Casonato","sequence":"additional","affiliation":[{"name":"Thrombohaemorrhagic Disorders Unit Department of Medicine University of Padua Padua 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