{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:14:32Z","timestamp":1785870872298,"version":"3.56.0"},"reference-count":31,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"name":"Italian Ministry of Health-Bando Ricerca Corrente"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>\n            Background\u2003Low von Willebrand factor (VWF) refers to subjects with plasma levels of 30 to 50\u2009IU\/dL. The mechanism of low VWF is poorly understood. We chose to determine the clinical presentation, laboratory phenotype, and underlying mechanisms of low VWF.<\/jats:p><jats:p>\n            Material and Methods\u2003We included 250 patients characterized with low VWF. The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) was used to assess clinical symptoms. To determine the underlying mechanisms of low VWF, we used as markers the VWF propeptide (VWFpp) assay and FVIII:C\/VWF:Ag ratio for VWF synthesis and the VWFpp\/VWF:Ag ratio for VWF clearance. Results were compared with those of 120 healthy controls. Cases with abnormal screening tests were further evaluated for coagulation factor levels and platelet disorders.<\/jats:p><jats:p>\n            Results\u2003The median age of the cohort was 35 years (range 3\u201385), 21% were children (n\u2009=\u200953), 34% were adult males (n\u2009=\u200985), and 45% (n\u2009=\u2009112) were adult females. According to the ISTH-BAT, abnormal bleeding was found in 35% of children, 47% of males, and 49% of females. No association was found between VWF activity levels and ISTH-BAT. Patients showed an overall decreased VWF synthesis\/secretion and an enhanced VWF clearance was identified in 33% of them. In 89 patients (36%), there were other hemostasis-related defects, but there was no difference in the ISTH-BAT between the two groups.<\/jats:p><jats:p>\n            Conclusion\u2003Our findings indicate that reduced VWF synthesis\/secretion and enhanced VWF clearance are major mechanisms of low VWF levels. Patients with low VWF have significant bleeding manifestations. While other hemostasis defects occurred together with low VWF, this combination did not exacerbate clinical symptoms.<\/jats:p>","DOI":"10.1055\/a-2186-6362","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:33:30Z","timestamp":1696577610000},"page":"340-350","source":"Crossref","is-referenced-by-count":14,"title":["Clinical and Laboratory Presentation and Underlying Mechanism in Patients with Low VWF"],"prefix":"10.1055","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-7879","authenticated-orcid":false,"given":"Omid","family":"Seidizadeh","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Ciavarella","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Baronciani","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Boggio","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ballardini","sequence":"additional","affiliation":[{"name":"Department of Oncology and Onco-Hematology, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Cozzi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Colpani","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Pagliari","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Novembrino","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Maria","family":"Siboni","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Milan, Italy"},{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"issue":"12","key":"ref1","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1111\/jth.12008","article-title":"von Willebrand factor: the old, the new and the unknown","volume":"10","author":"P J Lenting","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"09","key":"ref2","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1182\/blood-2014-05-378638","article-title":"von Willebrand factor, Jedi knight of the bloodstream","volume":"124","author":"T A Springer","year":"2014","journal-title":"Blood"},{"issue":"23","key":"ref3","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1182\/blood-2013-06-498303","article-title":"von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy","volume":"122","author":"D Lillicrap","year":"2013","journal-title":"Blood"},{"issue":"10","key":"ref4","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1111\/j.1538-7836.2006.02146.x","article-title":"Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor","volume":"4","author":"J E Sadler","year":"2006","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1182\/bloodadvances.2020003265","article-title":"ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease","volume":"5","author":"P D James","year":"2021","journal-title":"Blood Adv"},{"issue":"13","key":"ref6","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1182\/bloodadvances.2020002038","article-title":"Low VWF: insights into pathogenesis, diagnosis, and clinical management","volume":"4","author":"J S O'Donnell","year":"2020","journal-title":"Blood Adv"},{"issue":"S 01","key":"ref7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/ijlh.12653","article-title":"Controversies in the diagnosis of Type 1 von Willebrand disease","volume":"39","author":"M L Bowman","year":"2017","journal-title":"Int J Lab Hematol"},{"issue":"20","key":"ref8","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1182\/blood-2015-10-673681","article-title":"Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States","volume":"127","author":"V H Flood","year":"2016","journal-title":"Blood"},{"issue":"21","key":"ref9","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1182\/blood-2017-05-786699","article-title":"Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels","volume":"130","author":"M Lavin","year":"2017","journal-title":"Blood"},{"issue":"14","key":"ref10","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1182\/blood-2018-09-874636","article-title":"Increased galactose expression and enhanced clearance in patients with low von Willebrand factor","volume":"133","author":"S Aguila","year":"2019","journal-title":"Blood"},{"issue":"07","key":"ref11","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1182\/blood-2007-11-122945","article-title":"A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor","volume":"111","author":"L Gallinaro","year":"2008","journal-title":"Blood"},{"issue":"01","key":"ref12","first-page":"77","article-title":"A sensitive ristocetin co-factor activity assay with recombinant glycoprotein Ibalpha for the diagnosis of patients with low von Willebrand factor levels","volume":"89","author":"A B Federici","year":"2004","journal-title":"Haematologica"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.jtha.2023.01.012","article-title":"Genetic determinants of enhanced von Willebrand factor clearance from plasma","volume":"21","author":"O Seidizadeh","year":"2023","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1055\/s-0038-1660481","article-title":"Evaluation of the utility of von Willebrand factor propeptide in the differential diagnosis of von Willebrand disease and acquired von Willebrand syndrome","volume":"45","author":"F Stufano","year":"2019","journal-title":"Semin Thromb Hemost"},{"issue":"06","key":"ref15","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/hae.12503","article-title":"Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project","volume":"20","author":"M Elbatarny","year":"2014","journal-title":"Haemophilia"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1365-2516.2007.01643.x","article-title":"von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA)","volume":"14","author":"W L Nichols","year":"2008","journal-title":"Haemophilia"},{"issue":"04","key":"ref17","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/bjh.13064","article-title":"The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology","volume":"167","author":"M A Laffan","year":"2014","journal-title":"Br J Haematol"},{"issue":"06","key":"ref18","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1182\/blood-2002-09-2892","article-title":"Von Willebrand disease type 1: a diagnosis in search of a disease","volume":"101","author":"J E Sadler","year":"2003","journal-title":"Blood"},{"issue":"06","key":"ref19","doi-asserted-by":"crossref","first-page":"e718","DOI":"10.1097\/HS9.0000000000000718","article-title":"Importance of genotyping in von Willebrand disease to elucidate pathogenic mechanisms and variability in phenotype","volume":"6","author":"F Atiq","year":"2022","journal-title":"HemaSphere"},{"issue":"11","key":"ref20","doi-asserted-by":"crossref","first-page":"e3038","DOI":"10.1097\/MD.0000000000003038","article-title":"A laboratory phenotype\/genotype correlation of 1167 French patients from 670 families with von Willebrand disease: a new epidemiologic picture","volume":"95","author":"A Veyradier","year":"2016","journal-title":"Medicine (Baltimore)"},{"issue":"01","key":"ref21","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1182\/blood-2006-05-020784","article-title":"Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD)","volume":"109","author":"A Goodeve","year":"2007","journal-title":"Blood"},{"issue":"01","key":"ref22","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1182\/blood-2006-05-021105","article-title":"The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study","volume":"109","author":"P D James","year":"2007","journal-title":"Blood"},{"issue":"03","key":"ref23","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/jth.15227","article-title":"Criteria for low von Willebrand factor diagnosis and risk score to predict future bleeding","volume":"19","author":"F Atiq","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"14","key":"ref24","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1182\/bloodadvances.2018017418","article-title":"Significant gynecological bleeding in women with low von Willebrand factor levels","volume":"2","author":"M Lavin","year":"2018","journal-title":"Blood Adv"},{"issue":"05","key":"ref25","first-page":"428","article-title":"Von Willebrand disease combined with coagulation defects in Iran","volume":"19","author":"O Seidizadeh","year":"2021","journal-title":"Blood Transfus"},{"issue":"03","key":"ref26","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1182\/bloodadvances.2022007340","article-title":"Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp\/VWF:Ag ratio and clinical significance","volume":"7","author":"D Doherty","year":"2023","journal-title":"Blood Adv"},{"issue":"14","key":"ref27","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1182\/blood.2021010683","article-title":"Single-cell transcriptional analysis of human endothelial colony-forming cells from patients with low VWF levels","volume":"139","author":"C J Ng","year":"2022","journal-title":"Blood"},{"issue":"14","key":"ref28","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1182\/blood.2021013541","article-title":"Low von Willebrand factor phenotype: the enigma continues","volume":"139","author":"D Lillicrap","year":"2022","journal-title":"Blood"},{"issue":"12","key":"ref29","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1182\/blood-2012-09-455089","article-title":"VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease","volume":"121","author":"J Eikenboom","year":"2013","journal-title":"Blood"},{"issue":"19","key":"ref30","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1182\/blood-2014-09-603241","article-title":"von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease","volume":"125","author":"Y V Sanders","year":"2015","journal-title":"Blood"},{"issue":"05","key":"ref31","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1111\/jth.15658","article-title":"Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study","volume":"20","author":"M T Pagliari","year":"2022","journal-title":"J Thromb Haemost"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2186-6362.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T11:57:09Z","timestamp":1730807829000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2186-6362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,5]]},"references-count":31,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2024,3,26]]},"published-print":{"date-parts":[[2024,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2186-6362","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,10,5]]},"published":{"date-parts":[[2023,10,5]]}}}