{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:15:16Z","timestamp":1787004916617,"version":"build-2736575974"},"reference-count":58,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>von Willebrand disease (VWD) is the most common well-studied genetic bleeding disorder worldwide. Much less is known about platelet-type VWD (PT-VWD), a rare platelet function defect, and a \u201cnonidentical\u201d twin bleeding phenotype to type 2B VWD (2B-VWD). Rather than a defect in the von Willebrand factor (VWF) gene, PT-VWD is caused by a platelet GP1BA mutation leading to a hyperaffinity of the glycoprotein Ib\u03b1 (GPIb\u03b1) platelet surface receptor for VWF, and thus increased platelet clearing and high-molecular-weight VWF multimer elimination. Nine GP1BA gene mutations are known. It is historically believed that this enhanced binding was enabled by the \u03b2-switch region of GPIb\u03b1 adopting an extended \u03b2-hairpin form. Recent evidence suggests the pathological conformation that destabilizes the compact triangular form of the R-loop\u2014the GPIb\u03b1 protein's region for VWF binding. PT-VWD is often misdiagnosed as 2B-VWD, even the though distinction between the two is crucial for proper treatment, as the former requires platelet transfusions, while the latter requires VWF\/FVIII concentrate administration. Nevertheless, these PT-VWD treatments remain unsatisfactory, owing to their high cost, low availability, risk of alloimmunity, and the need to carefully balance platelet administration. Antibodies such as 6B4 remain undependable as an alternative therapy due to their questionable efficacy and high costs for this purpose. On the other hand, synthetic peptide therapeutics developed with In-Silico Protein Synthesizer to disrupt the association between GPIb\u03b1 and VWF show preliminary promise as a therapy based on in vitro experiments. Such peptides could serve as an effective diagnostic technology for discriminating between 2B-VWD and PT-VWD, or potentially all forms of VWD, based on their high specificity. This field is rapidly growing and the current review sheds light on the complex pathology and some novel potential therapeutic and diagnostic strategies.<\/jats:p>","DOI":"10.1055\/s-0044-1789183","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T19:33:25Z","timestamp":1724787205000},"page":"219-226","source":"Crossref","is-referenced-by-count":12,"title":["Platelet-Type von Willebrand Disease: Complex Pathophysiology and Insights on Novel Therapeutic and Diagnostic Strategies"],"prefix":"10.1055","volume":"51","author":[{"given":"Anne","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, School of Medicine, Queen's University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.D.","family":"Kazmirchuk","sequence":"additional","affiliation":[{"name":"Department of Biology, and the Ottawa Institute of Systems Biology (OISB), Carleton University, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Bradbury-Jost","sequence":"additional","affiliation":[{"name":"Department of Biology, and the Ottawa Institute of Systems Biology (OISB), Carleton University, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashkan","family":"Golshani","sequence":"additional","affiliation":[{"name":"Department of Biology, and the Ottawa Institute of Systems Biology (OISB), Carleton University, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, School of Medicine, Queen's University, Kingston, Ontario, Canada"},{"name":"School of Baccalaureate Nursing, St. Lawrence College, Kingston, Ontario, Canada"},{"name":"Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura City, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"issue":"05","key":"ref1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1055\/s-0031-1281030","article-title":"Platelet-type von Willebrand disease: a rare, often misdiagnosed and underdiagnosed bleeding disorder","volume":"37","author":"M Othman","year":"2011","journal-title":"Semin Thromb Hemost"},{"issue":"08","key":"ref2","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1055\/s-2007-1000368","article-title":"Platelet-type von Willebrand disease and type 2B von Willebrand disease: a story of nonidentical twins when two different genetic abnormalities evolve into similar phenotypes","volume":"33","author":"M Othman","year":"2007","journal-title":"Semin Thromb Hemost"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/ajh.2830100113","article-title":"Von Willebrand disease associated with familial thrombocytopenia and increased ristocetin-induced platelet aggregation","volume":"10","author":"H Takahashi","year":"1981","journal-title":"Am J Hematol"},{"issue":"06","key":"ref4","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1056\/NEJM198202113060603","article-title":"Pseudo-von Willebrand's disease. 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