{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T03:18:21Z","timestamp":1771039101086,"version":"3.50.1"},"reference-count":96,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>von Willebrand disease (VWD) is a very heterogenous disease, resulting in different phenotypes and different degrees of bleeding severity. Established therapies (i.e., desmopressin, antifibrinolytic agents, hormone therapy for heavy menstrual bleeding, and von Willebrand factor [VWF] concentrates) may work in some subtypes, but not in all patients. In recent years, progress has been made in improving the diagnosis of VWD subtypes, allowing for more specific therapy. The impact of VWD on women's daily lives has also come to the fore in recent years, with hormone therapy, tranexamic acid, or recombinant VWF as treatment options. New treatment approaches, including the replacement of lacking factor VIII (FVIII) function, may work in those subgroups affected by severe FVIII deficiency. Reducing the clearance of VWF is an alternative treatment pathway; for example, rondaptivon pegol is a VWFA1 domain-binding aptamer which not only improves plasma VWF\/FVIII levels, but also corrects platelet counts in thrombocytopenic type 2B VWD patients. These approaches are currently in clinical development, which will be the focus of this review. In addition, half-life extension methods are also important for the improvement of patients' quality of life. Targeting specific mutations may further lead to personalized treatments in the future. Finally, a few randomized controlled trials, although relatively small, have been published in recent years, aiming to achieve a higher level of evidence in future guidelines.<\/jats:p>","DOI":"10.1055\/s-0044-1779485","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T23:59:50Z","timestamp":1707436790000},"page":"720-732","source":"Crossref","is-referenced-by-count":9,"title":["Progress in von Willebrand Disease Treatment: Evolution towards Newer Therapies"],"prefix":"10.1055","volume":"50","author":[{"given":"Miriam M.","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Schoergenhofer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Jilma","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"issue":"16","key":"ref1","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1182\/blood-2013-03-493312","article-title":"Accelerated uptake of VWF\/platelet complexes in macrophages contributes to VWD type 2B-associated thrombocytopenia","volume":"122","author":"C Casari","year":"2013","journal-title":"Blood"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1055\/s-0037-1613992","article-title":"Impact, diagnosis and treatment of von Willebrand disease","volume":"84","author":"J E Sadler","year":"2000","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref3","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1055\/s-0040-1713735","article-title":"Navigating the myriad of von Willebrand factor assays","volume":"40","author":"E J Favaloro","year":"2020","journal-title":"Hamostaseologie"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.pathol.2016.03.001","article-title":"Laboratory tests used to help diagnose von Willebrand disease: an update","volume":"48","author":"E J Favaloro","year":"2016","journal-title":"Pathology"},{"issue":"17","key":"ref5","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1182\/blood.2020008501","article-title":"von Willebrand disease: what does the future hold?","volume":"137","author":"C V Denis","year":"2021","journal-title":"Blood"},{"issue":"01","key":"ref6","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":"21","key":"ref7","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1056\/NEJMra1601561","article-title":"von Willebrand's disease","volume":"375","author":"F WG Leebeek","year":"2016","journal-title":"N Engl J Med"},{"issue":"10","key":"ref8","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"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.thromres.2015.11.002","article-title":"Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent","volume":"137","author":"P Jilma-Stohlawetz","year":"2016","journal-title":"Thromb Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1159894","DOI":"10.3389\/fcvm.2023.1159894","article-title":"Shear-induced acquired von Willebrand syndrome: an accomplice of bleeding events in adults on extracorporeal membrane oxygenation support","volume":"10","author":"H Wang","year":"2023","journal-title":"Front Cardiovasc Med"},{"issue":"01","key":"ref11","first-page":"58","article-title":"von Willebrand factor abnormalities in aortic valve stenosis: pathophysiology and impact on bleeding","volume":"106","author":"A Casonato","year":"2011","journal-title":"Thromb Haemost"},{"issue":"08","key":"ref12","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.3324\/haematol.2020.255117","article-title":"Acquired von Willebrand syndrome: focused for hematologists","volume":"105","author":"M Franchini","year":"2020","journal-title":"Haematologica"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/ajh.10327","article-title":"Health status and health-related quality of life associated with von Willebrand disease","volume":"73","author":"R D Barr","year":"2003","journal-title":"Am J Hematol"},{"issue":"05","key":"ref14","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.3892\/etm.2016.3144","article-title":"Heavy menstrual bleeding and health-associated quality of life in women with von Willebrand's disease","volume":"11","author":"I Govorov","year":"2016","journal-title":"Exp Ther Med"},{"issue":"09","key":"ref15","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1089\/jwh.2022.0082","article-title":"Impact of von Willebrand disease on women's health outcomes: a matched cohort database study","volume":"31","author":"K W Hagberg","year":"2022","journal-title":"J Womens Health (Larchmt)"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1182\/bloodadvances.2021005589","article-title":"Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature","volume":"6","author":"R Brignardello-Petersen","year":"2022","journal-title":"Blood Adv"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1182\/bloodadvances.2020003264","article-title":"ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease","volume":"5","author":"N T Connell","year":"2021","journal-title":"Blood Adv"},{"issue":"977","key":"ref18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/pgmj.2006.052118","article-title":"How do you treat bleeding disorders with desmopressin?","volume":"83","author":"B Ozg\u00f6nenel","year":"2007","journal-title":"Postgrad Med J"},{"issue":"04","key":"ref19","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1046\/j.1538-7836.2003.00190.x","article-title":"Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP)","volume":"1","author":"J E Kaufmann","year":"2003","journal-title":"J Thromb Haemost"},{"issue":"07","key":"ref20","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1182\/blood-2007-08-109231","article-title":"Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD","volume":"111","author":"G Castaman","year":"2008","journal-title":"Blood"},{"issue":"03","key":"ref21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/bjh.16681","article-title":"New developments in von Willebrand disease","volume":"191","author":"H Fogarty","year":"2020","journal-title":"Br J Haematol"},{"issue":"S 01","key":"ref22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1365-2516.2007.01610.x","article-title":"The use of desmopressin in von Willebrand disease: the experience of the first 30 years (1977-2007)","volume":"14","author":"A B Federici","year":"2008","journal-title":"Haemophilia"},{"issue":"21","key":"ref23","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1182\/bloodadvances.2019000368","article-title":"New therapies for von Willebrand disease","volume":"3","author":"P M Mannucci","year":"2019","journal-title":"Blood Adv"},{"issue":"18","key":"ref24","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.1182\/bloodadvances.2021006757","article-title":"Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease","volume":"6","author":"F Atiq","year":"2022","journal-title":"Blood Adv"},{"issue":"06","key":"ref25","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1046\/j.1365-2516.2002.00678.x","article-title":"DDAVP nasal spray for treatment of menorrhagia in women with inherited bleeding disorders: a randomized placebo-controlled crossover study","volume":"8","author":"R A Kadir","year":"2002","journal-title":"Haemophilia"},{"issue":"08","key":"ref26","first-page":"e44310","article-title":"Desmopressin as a treatment in patients with von Willebrand disease: a systematic review","volume":"15","author":"A Beltran","year":"2023","journal-title":"Cureus"},{"issue":"05","key":"ref27","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.athoracsur.2011.01.052","article-title":"Patients with severe aortic valve stenosis and impaired platelet function benefit from preoperative desmopressin infusion","volume":"91","author":"B Steinlechner","year":"2011","journal-title":"Ann Thorac Surg"},{"issue":"05","key":"ref28","first-page":"391","article-title":"A phase III study comparing secondary long-term prophylaxis versus on-demand treatment with vWF\/FVIII concentrates in severe inherited von Willebrand disease","volume":"17","author":"F Peyvandi","year":"2019","journal-title":"Blood Transfus"},{"issue":"05","key":"ref29","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1182\/blood-2013-01-479527","article-title":"Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial","volume":"122","author":"P M Mannucci","year":"2013","journal-title":"Blood"},{"issue":"12","key":"ref30","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1182\/blood.V79.12.3130.bloodjournal79123130","article-title":"Comparison of four virus-inactivated plasma concentrates for treatment of severe von Willebrand disease: a cross-over randomized trial","volume":"79","author":"P M Mannucci","year":"1992","journal-title":"Blood"},{"issue":"06","key":"ref31","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1160\/TH06-09-0495","article-title":"Comparison of the pharmacokinetics of two von Willebrand factor concentrates [Biostate and AHF (high purity)] in people with von Willebrand disorder. A randomised cross-over, multi-centre study","volume":"97","author":"E J Favaloro","year":"2007","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref32","first-page":"279","article-title":"The pharmacokinetic diversity of two von Willebrand factor (VWF)\/ factor VIII (FVIII) concentrates in subjects with congenital von Willebrand disease. Results from a prospective, randomised crossover study","volume":"106","author":"C M Kessler","year":"2011","journal-title":"Thromb Haemost"},{"issue":"S 01","key":"ref33","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1055\/s-0037-1617202","article-title":"Development of a plasma- and albumin-free recombinant von Willebrand factor","volume":"29","author":"P L Turecek","year":"2009","journal-title":"Hamostaseologie"},{"issue":"02","key":"ref34","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1080\/09537104.2017.1420153","article-title":"Sensitive and specific assessment of recombinant von Willebrand factor in platelet function analyzer","volume":"30","author":"I Pekrul","year":"2019","journal-title":"Platelets"},{"issue":"S 01","key":"ref35","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/01.mbc.0000167657.85143.ad","article-title":"Shear stress and the role of high molecular weight von Willebrand factor multimers in thrombus formation","volume":"16","author":"J A L\u00f3pez","year":"2005","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"03","key":"ref36","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/ajh.2830450303","article-title":"von Willebrand's disease: use of collagen binding assay provides potential improvement to laboratory monitoring of desmopressin (DDAVP) therapy","volume":"45","author":"E J Favaloro","year":"1994","journal-title":"Am J Hematol"},{"issue":"02","key":"ref37","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1046\/j.1365-2516.2001.00487.x","article-title":"Laboratory diagnosis of von Willebrand disorder (vWD) and monitoring of DDAVP therapy: efficacy of the PFA-100 and vWF:CBA as combined diagnostic strategies","volume":"7","author":"E J Favaloro","year":"2001","journal-title":"Haemophilia"},{"issue":"06","key":"ref38","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/MBC.0b013e32832da1ad","article-title":"Potential supplementary utility of combined PFA-100 and functional von Willebrand factor testing for the laboratory assessment of desmopressin and factor concentrate therapy in von Willebrand disease","volume":"20","author":"E J Favaloro","year":"2009","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"06","key":"ref39","doi-asserted-by":"crossref","first-page":"e0179566","DOI":"10.1371\/journal.pone.0179566","article-title":"Type 2B von Willebrand disease with or without large multimers: a distinction of the two sides of the disorder is long overdue","volume":"12","author":"A Casonato","year":"2017","journal-title":"PLoS ONE"},{"issue":"18","key":"ref40","doi-asserted-by":"crossref","first-page":"5467","DOI":"10.1182\/bloodadvances.2022007805","article-title":"The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF\/FVIII in type 2B von Willebrand disease","volume":"6","author":"C Ay","year":"2022","journal-title":"Blood Adv"},{"issue":"02","key":"ref41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1182\/blood.2021014810","article-title":"Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results","volume":"140","author":"F WG Leebeek","year":"2022","journal-title":"Blood"},{"issue":"01","key":"ref42","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/jth.14313","article-title":"Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery","volume":"17","author":"F Peyvandi","year":"2019","journal-title":"J Thromb Haemost"},{"issue":"21","key":"ref43","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1182\/blood.2020009144","article-title":"Gill JC, Castaman G, Windyga J, et al. Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015;126(17):2038-2046","volume":"136","author":"J C Gill","year":"2020","journal-title":"Blood"},{"issue":"06","key":"ref44","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1007\/s12630-021-01967-7","article-title":"Tranexamic acid: current use in obstetrics, major orthopedic, and trauma surgery","volume":"68","author":"J Wong","year":"2021","journal-title":"Can J Anaesth"},{"issue":"03","key":"ref45","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1213\/ANE.0000000000006039","article-title":"Update on applications and limitations of perioperative tranexamic acid","volume":"135","author":"P A Patel","year":"2022","journal-title":"Anesth Analg"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0140-6736(10)60835-5","article-title":"Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial","volume":"376","author":"H Shakur","year":"2010","journal-title":"Lancet"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/S0140-6736(19)32233-0","article-title":"Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial","volume":"394","author":"CRASH-3 Trial Collaborators","year":"2019","journal-title":"Lancet"},{"issue":"08","key":"ref48","doi-asserted-by":"crossref","first-page":"e612","DOI":"10.1016\/S2352-3026(23)00119-9","article-title":"Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial","volume":"10","author":"M V Ragni","year":"2023","journal-title":"Lancet Haematol"},{"issue":"S 03","key":"ref49","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/hae.14050","article-title":"von Willebrand disease: diagnosis and treatment, treatment of women, and genomic approach to diagnosis","volume":"27","author":"M Laffan","year":"2021","journal-title":"Haemophilia"},{"issue":"04","key":"ref52","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1056\/NEJMoa2209226","article-title":"Efanesoctocog alfa prophylaxis for patients with severe Hemophilia A","volume":"388","author":"A von Drygalski","year":"2023","journal-title":"N Engl J Med"},{"issue":"11","key":"ref53","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa2002699","article-title":"BIVV001 fusion protein as factor VIII replacement therapy for Hemophilia A","volume":"383","author":"B A Konkle","year":"2020","journal-title":"N Engl J Med"},{"issue":"10","key":"ref54","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1055\/s-0040-1714279","article-title":"Bridging the missing link with emicizumab: a bispecific antibody for treatment of Hemophilia A","volume":"120","author":"G Gelbenegger","year":"2020","journal-title":"Thromb Haemost"},{"issue":"09","key":"ref55","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1703068","article-title":"Emicizumab prophylaxis in Hemophilia A with inhibitors","volume":"377","author":"J Oldenburg","year":"2017","journal-title":"N Engl J Med"},{"issue":"01","key":"ref56","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/hae.14450","article-title":"Off-label use of emicizumab in persons with acquired haemophilia A and von Willebrand disease: a scoping review of the literature","volume":"28","author":"V M Thomas","year":"2022","journal-title":"Haemophilia"},{"issue":"02","key":"ref57","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/hae.14491","article-title":"Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): report of two cases and review of literature","volume":"28","author":"C Shanmukhaiah","year":"2022","journal-title":"Haemophilia"},{"issue":"S 04","key":"ref58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/hae.14518","article-title":"Towards novel treatment options in von Willebrand disease","volume":"28","author":"P J Lenting","year":"2022","journal-title":"Haemophilia"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"102530","DOI":"10.1016\/j.bcmd.2020.102530","article-title":"The potential role of emicizumab prophylaxis in severe von Willebrand disease","volume":"87","author":"A A Barg","year":"2021","journal-title":"Blood Cells Mol Dis"},{"issue":"02","key":"ref60","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1111\/hae.14272","article-title":"Emicizumab improves thrombus formation of type 2A von willebrand disease under high shear condition","volume":"27","author":"H Yaoi","year":"2021","journal-title":"Haemophilia"},{"issue":"05","key":"ref61","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/hae.14581","article-title":"Emicizumab enhances thrombus formation in vitro under high shear flow conditions in whole blood from patients with type 1 and type 3 von Willebrand disease","volume":"28","author":"H Yaoi","year":"2022","journal-title":"Haemophilia"},{"issue":"18","key":"ref62","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1182\/bloodadvances.2019000656","article-title":"Efficacy of emicizumab in a pediatric patient with type 3 von Willebrand disease and alloantibodies","volume":"3","author":"A C Weyand","year":"2019","journal-title":"Blood Adv"},{"issue":"09","key":"ref64","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1182\/blood-2011-08-373605","article-title":"Macrophage LRP1 contributes to the clearance of von Willebrand factor","volume":"119","author":"G Rastegarlari","year":"2012","journal-title":"Blood"},{"issue":"08","key":"ref65","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3324\/haematol.2009.019927","article-title":"Reduced survival of type 2B von Willebrand factor, irrespective of large multimer representation or thrombocytopenia","volume":"95","author":"A Casonato","year":"2010","journal-title":"Haematologica"},{"issue":"23","key":"ref66","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.1182\/blood-2009-11-254193","article-title":"Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B","volume":"115","author":"J Rayes","year":"2010","journal-title":"Blood"},{"issue":"02","key":"ref67","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1160\/TH07-10-0629","article-title":"Clearance of von Willebrand factor","volume":"99","author":"C V Denis","year":"2008","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref68","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1182\/blood-2008-01-133181","article-title":"Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo","volume":"112","author":"C J van Schooten","year":"2008","journal-title":"Blood"},{"issue":"13","key":"ref69","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1182\/blood-2014-06-528406","article-title":"von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends","volume":"125","author":"P J Lenting","year":"2015","journal-title":"Blood"},{"issue":"09","key":"ref70","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.3324\/haematol.2021.279948","article-title":"The von Willebrand factor A-1 domain binding aptamer BT200 elevates plasma levels of von Willebrand factor and factor VIII: a first-in-human trial","volume":"107","author":"K D Kovacevic","year":"2022","journal-title":"Haematologica"},{"issue":"03","key":"ref71","first-page":"563","article-title":"A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease","volume":"104","author":"B Jilma","year":"2010","journal-title":"Thromb Haemost"},{"issue":"23","key":"ref72","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1161\/CIRCULATIONAHA.107.724864","article-title":"First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers","volume":"116","author":"J C Gilbert","year":"2007","journal-title":"Circulation"},{"issue":"03","key":"ref73","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1160\/TH10-08-0520","article-title":"Inhibition of von Willebrand factor by ARC1779 in patients with acute thrombotic thrombocytopenic purpura","volume":"105","author":"P Jilma-Stohlawetz","year":"2011","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref74","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1537-2995.2009.02554.x","article-title":"The aptamer ARC1779 blocks von Willebrand factor-dependent platelet function in patients with thrombotic thrombocytopenic purpura ex vivo","volume":"50","author":"F B Mayr","year":"2010","journal-title":"Transfusion"},{"issue":"03","key":"ref75","first-page":"539","article-title":"A dose ranging phase I\/II trial of the von Willebrand factor inhibiting aptamer ARC1779 in patients with congenital thrombotic thrombocytopenic purpura","volume":"106","author":"P Jilma-Stohlawetz","year":"2011","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref76","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1111\/jth.14755","article-title":"The development and characterization of a long acting anti-thrombotic von Willebrand factor (VWF) aptamer","volume":"18","author":"S Zhu","year":"2020","journal-title":"J Thromb Haemost"},{"issue":"03","key":"ref77","doi-asserted-by":"crossref","first-page":"211","DOI":"10.5482\/HAMO-14-12-0081","article-title":"Interaction of von Willebrand factor with platelets and the vessel wall","volume":"35","author":"Z M Ruggeri","year":"2015","journal-title":"Hamostaseologie"},{"key":"ref78","doi-asserted-by":"crossref","DOI":"10.1016\/j.rpth.2023.100541","volume-title":"Aptamer BT200 Prolongs VWF half-life by Blocking Interaction with Macrophage Scavenger Receptor LRP1","author":"A Chion","year":"2023"},{"issue":"06","key":"ref79","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1111\/jth.14785","article-title":"Investigating the clearance of VWF A-domains using site-directed PEGylation and novel N-linked glycosylation","volume":"18","author":"J Fazavana","year":"2020","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref80","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1182\/blood.2022016571","article-title":"The von Willebrand factor-binding aptamer rondaptivon pegol as a treatment for severe and nonsevere hemophilia A","volume":"141","author":"C Ay","year":"2023","journal-title":"Blood"},{"issue":"03","key":"ref81","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1182\/blood-2008-04-152280","article-title":"Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients","volume":"113","author":"A B Federici","year":"2009","journal-title":"Blood"},{"issue":"01","key":"ref82","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-2141.1988.tb07602.x","article-title":"IIB von Willebrand's disease: pathogenetic and therapeutic studies","volume":"69","author":"P A Kyrle","year":"1988","journal-title":"Br J Haematol"},{"issue":"05","key":"ref83","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/jth.12885","article-title":"Shear stress-independent binding of von Willebrand factor-type 2B mutants p.R1306Q & p.V1316M to LRP1 explains their increased clearance","volume":"13","author":"N Wohner","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref84","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13045-017-0407-1","article-title":"A novel monoclonal antibody against the von Willebrand factor A2 domain reduces its cleavage by ADAMTS13","volume":"10","author":"L Zhang","year":"2017","journal-title":"J Hematol Oncol"},{"issue":"04","key":"ref85","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1160\/TH14-09-0731","article-title":"VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP","volume":"113","author":"M Schwameis","year":"2015","journal-title":"Thromb Haemost"},{"issue":"09","key":"ref86","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1182\/bloodadvances.2021006353","article-title":"A novel mouse model of type 2N VWD was developed by CRISPR\/Cas9 gene editing and recapitulates human type 2N VWD","volume":"6","author":"Q Shi","year":"2022","journal-title":"Blood Adv"},{"issue":"23","key":"ref88","first-page":"2891","article-title":"Efficacy of platelet-inspired hemostatic nanoparticles on bleeding in von Willebrand disease murine models","volume":"141","author":"S Roullet","year":"2023","journal-title":"Blood"},{"issue":"24","key":"ref89","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.1182\/blood-2010-02-268920","article-title":"The dominant-negative von Willebrand factor gene deletion p.P1127_C1948delinsR: molecular mechanism and modulation","volume":"116","author":"C Casari","year":"2010","journal-title":"Blood"},{"issue":"11","key":"ref90","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1055\/s-0040-1715442","article-title":"Ex vivo improvement of a von Willebrand disease type 2A phenotype using an allele-specific small-interfering RNA","volume":"120","author":"A de Jong","year":"2020","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref91","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/jth.15131","article-title":"In vivo modulation of a dominant-negative variant in mouse models of von Willebrand disease type 2A","volume":"19","author":"M Campioni","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref92","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/rth2.12242","article-title":"Alternative trafficking of Weibel-Palade body proteins in CRISPR\/Cas9-engineered von Willebrand factor-deficient blood outgrowth endothelial cells","volume":"3","author":"M Schillemans","year":"2019","journal-title":"Res Pract Thromb Haemost"},{"issue":"12","key":"ref93","doi-asserted-by":"crossref","first-page":"4728","DOI":"10.1182\/blood-2005-09-3605","article-title":"Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor","volume":"107","author":"S F De Meyer","year":"2006","journal-title":"Blood"},{"issue":"04","key":"ref94","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1160\/TH12-04-0244","article-title":"Determinants of bleeding phenotype in adult patients with moderate or severe von Willebrand disease","volume":"108","author":"E M de Wee","year":"2012","journal-title":"Thromb Haemost"},{"issue":"08","key":"ref95","doi-asserted-by":"crossref","first-page":"e561","DOI":"10.1016\/S2352-3026(23)00165-5","article-title":"Heavy menstrual blood loss in patients with von Willebrand disease: an unsolved problem","volume":"10","author":"F WG Leebeek","year":"2023","journal-title":"Lancet Haematol"},{"issue":"07","key":"ref96","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1111\/jth.15713","article-title":"Molecular pathogenesis and heterogeneity in type 3 VWD families in U.S. Zimmerman program","volume":"20","author":"P A Christopherson","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref97","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1055\/s-0037-1599145","article-title":"Angiodysplasia in von Willebrand disease: understanding the clinical and basic science","volume":"43","author":"S Selvam","year":"2017","journal-title":"Semin Thromb Hemost"},{"issue":"02","key":"ref98","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1182\/blood-2018-01-769018","article-title":"von Willebrand factor regulation of blood vessel formation","volume":"132","author":"A M Randi","year":"2018","journal-title":"Blood"},{"issue":"02","key":"ref99","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1055\/s-2002-27821","article-title":"Von Willebrand factor collagen-binding (activity) assay in the diagnosis of von Willebrand disease: a 15-year journey","volume":"28","author":"E J Favaloro","year":"2002","journal-title":"Semin Thromb Hemost"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2147\/JBM.S377126","article-title":"Structure and function of recombinant versus plasma-derived von Willebrand factor and impact on multimer pharmacokinetics in von Willebrand disease","volume":"13","author":"H Gritsch","year":"2022","journal-title":"J Blood Med"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0044-1779485.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T11:18:51Z","timestamp":1730805531000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0044-1779485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":96,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2024,6,11]]},"published-print":{"date-parts":[[2024,7]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0044-1779485","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]}}}