[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-448264-105":59,"doc-detail-448264-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","structure-and-multiple-functions-of-von-willebrand-factor-review-series","Structure and multiple functions of von Willebrand factor - Review Series","","Review of von Willebrand factor (VWF) biology since the original description of von Willebrand disease (VWD) in 1926. Explains how VWF biosynthesis occurs only in endothelial cells and megakaryocytes and relies on post-translational modifications such as glycosylation and multimerization, enabling roles in primary hemostasis and supporting secondary hemostasis via factor VIII protection. Summarizes ligand discovery and emerging non-hemostatic functions, outlining mechanisms that may enable anti-VWF therapeutic strategies.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/structure-and-multiple-functions-of-von-willebrand-factor-review-series/448264/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/structure-and-multiple-functions-of-von-willebrand-factor-review-series/448264.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Where is von Willebrand factor (VWF) biosynthesized under normal conditions?","Question",{"text":113,"@type":114},"VWF is synthesized exclusively in endothelial cells and megakaryocytes, where it undergoes complex intracellular processing.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do post-translational modifications contribute to VWF function?",{"text":118,"@type":114},"Biosynthesis involves modifications such as glycosylation and multimerization, which are key for enabling VWF hemostatic functions.",{"name":120,"@type":111,"acceptedAnswer":121},"What are the hemostatic roles of VWF in normal hemostasis?",{"text":122,"@type":114},"VWF binds exposed collagen to tether platelets for primary hemostasis and also functions as a chaperone that protects factor VIII from proteolysis and premature clearance, supporting secondary hemostasis.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},448264,1790791593,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","REVIEW SERIES  \nStructure and multiple functions of von Willebrand factor  \nSandra L. Haberichter1 and James S. O’Donnell2,3  \n1Versiti -Diagnostic Laboratories and Blood Research Institute, Milwaukee, WI, USA; 2 Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland and 3 National Coagulation Centre, St James’s Hospital, Dublin, Ireland  \nCorrespondence: J. O’Donnell  \n[jamesodonnell@rcsi.ie](jamesodonnell@rcsi.ie)  \nReceived: April 30, 2025.  \nAccepted: August 26, 2025.  \n[https://doi.org/10.3324/haematol.2024.286029](https://doi.org/10.3324/haematol.2024.286029)  \n©2026 Ferrata Storti Foundation  \nPublished under a CC BY-NC license   \nAbstract  \nSince the first description of a patient with von Willebrand disease (VWD) back in 1926, significant advances have been made in understanding the biology of von Willebrand factor (VWF) . Under normal conditions, in vivo biosynthesis of VWF is restricted to endothelial cells and megakaryocytes only. This biosynthesis involves complex post-translational modifications (including glycosylation and multimerization) which play a key role in enabling the hemostatic functions of VWF. As a result, VWF circulates in normal plasma as a series of heterogeneous multimers that can modulate tethering of platelets and primary hemostasis at sites of vascular injury. In addition, VWF also influences secondary hemostasis by serving as a chaperone molecule and protecting factor VIII from proteolysis and premature clearance. The molecular mechanisms underlying the pro-hemostatic functions of VWF have been comprehensively characterized. These insights serve to underpin the current classification of different VWD subtypes. Interestingly, accumulating evidence over the past decade has identified an array of new ligands that are able to bind to VWF. Consistent with these data, recent studies have further suggested a series of novel and non-hemostatic biological functions for VWF. These include potential roles for VWF in regulating inflammation, wound healing, angiogenesis and tumor cell metastasis. Further research in the coming years will be required to determine the clinical significance of these non-hemostatic roles of VWF. Defining the molecular mechanisms involved may offer exciting opportunities to develop novel anti-VWF targeted treatment approaches for important unmet clinical needs.  \nIntroduction  \nVon Willebrand factor (VWF) is a complex multimeric plasma glycoprotein that plays critical roles in normal hemostasis 1,2 First, VWF binds to exposed collagen at sites of vascular injury and then tethers platelets to the site of injury. Second, VWF also serves as a chaperone protein for factor VIII (FVIII) .3,4 Studies over many years have demonstrated that quantitative and/or qualitative reductions in plasma VWF activity result in von Willebrand disease (VWD) 1,5 Conversely, elevated plasma VWF-FVIII complex levels are a risk factor for both venous and arterial thrombosis.6,7 In this manuscript, we review our current understanding of the biosynthesis and structure of VWF. In addition, we further consider the mechanisms through which this multimeric glycoprotein can play such a critical role in normal hemostasis. Finally, we discuss accumulating recent evidence that VWF may have novel biological functions extending beyond coagulation.  \nStructure of von Willebrand factor  \nThe VWF gene is localized to chromosome 12 and contains 52 exons that span approximately 178 kb with exon size varying between 40 bp and 1.4 kb for exon 28.8 The primary translation product is a 2,813 amino acid protein. The N-terminal portion of VWF includes a hydrophobic 22-amino acid signal peptide followed by a 741-amino acid propeptide (VWFpp) and the 2,050-amino acid mature VWF protein (Figure 1A) . During biosynthesis, the propeptide is removed from the mature VWF protein proteolytically by the enzyme furin (Figure 1A) . The VWF protein was histori","cbCaijhfNqeGlTEX","https://ap.wps.com/l/cbCaijhfNqeGlTEX","pdf",2149812,11,"English","# Abstract\n# Introduction\n# Structure of von Willebrand factor\n## VWF gene and domain organization\n# Biosynthesis of von Willebrand factor","[{\"question\":\"Where is von Willebrand factor (VWF) biosynthesized under normal conditions?\",\"answer\":\"VWF is synthesized exclusively in endothelial cells and megakaryocytes, where it undergoes complex intracellular processing.\"},{\"question\":\"How do post-translational modifications contribute to VWF function?\",\"answer\":\"Biosynthesis involves modifications such as glycosylation and multimerization, which are key for enabling VWF hemostatic functions.\"},{\"question\":\"What are the hemostatic roles of VWF in normal hemostasis?\",\"answer\":\"VWF binds exposed collagen to tether platelets for primary hemostasis and also functions as a chaperone that protects factor VIII from proteolysis and premature clearance, supporting secondary hemostasis.\"}]","Structure and multiple functions of von Willebrand factor - Review Series | PDF",1790726318,28]