{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVon Willebrand factor (VWF) is a large, multimeric glycoprotein that plays a central role in hemostasis by mediating platelet adhesion and aggregation at sites of vascular injury. Upon vessel damage and under high shear stress, VWF binds to exposed subendothelial collagen and undergoes a conformational change that enables the binding of platelet glycoprotein Ibalpha (GPIbα). This initial interaction slows platelets down and promotes rolling and stable adhesion, a process that is further enhanced when VWF forms string‐like structures on injured endothelial surfaces to capture circulating platelets. These adhesive functions are critical not only for normal hemostasis but also contribute to thrombus formation in pathological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe activity of VWF is tightly regulated by mechanochemical cues. Hydrodynamic shear forces extend VWF multimers so as to expose cryptic binding sites within the A1 domain for GPIbα and to unveil a cleavage site in the A2 domain for the metalloprotease ADAMTS13. This shear‐induced unfolding enables a force‐dependent “catch” and “slip” bonding behavior that governs platelet interaction and, simultaneously, renders VWF susceptible to proteolysis. By cleaving ultra‐large VWF multimers into smaller, less hemostatically active forms, ADAMTS13 maintains a balance between effective platelet plug formation and prevention of pathological thrombosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "18"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its adhesive role, the structural complexity and regulated secretion of VWF underpin its diverse vascular functions. VWF is stored in endothelial Weibel–Palade bodies and is secreted in a regulated manner, where its modular organization (featuring distinct D, A, and C domains) governs both self‐association and interactions with other molecules. Structural studies have revealed that intramolecular arrangements—such as the shielding by the D′D3 region—modulate the availability of the A1 domain for platelet binding. Genetic mutations and polymorphisms in VWF not only cause quantitative and qualitative defects (as observed in various types of von Willebrand disease) but may also affect its interactions with other vascular regulators, including osteoprotegerin, thereby linking VWF to inflammation and angiogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "29"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, the regulation and plasma concentration of VWF have significant implications. Altered plasma levels or functional defects in VWF are associated with bleeding disorders such as von Willebrand disease and contribute to thrombotic conditions including thrombotic thrombocytopenic purpura, myocardial infarction, and ischemic stroke. Moreover, therapeutic interventions that target VWF interactions—whether by modulating its proteolytic processing, interfering with its binding to platelet receptors, or affecting its clearance—underscore its dual role as both a biomarker and an effector in vascular disease. The integration of genetic studies with functional assays has further refined our understanding of how VWF variants, together with factors such as ADAMTS13 levels and blood group determinants, influence thrombotic risk and bleeding tendency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "36"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gregor Theilmeier, Carine Michiels, Erik Spaepen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood.v99.12.4486"}], "href": "https://doi.org/10.1182/blood.v99.12.4486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12036879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12036879"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eric G Huizinga, Shizuko Tsuji, Roland A P Romijn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.107355"}], "href": "https://doi.org/10.1126/science.107355"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12183630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12183630"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Armin J Reininger, Harry F G Heijnen, Hannah Schumann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-02-0618"}], "href": "https://doi.org/10.1182/blood-2005-02-0618"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16449527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16449527"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zaverio M Ruggeri "}, {"type": "b", "children": [{"type": "t", "text": "The role of von Willebrand factor in thrombus formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.thromres.2007.03.011"}], "href": "https://doi.org/10.1016/j.thromres.2007.03.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17493665"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17493665"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alexander O Spiel, James C Gilbert, Bernd Jilma "}, {"type": "b", "children": [{"type": "t", "text": "von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.107.722827"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.107.722827"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18347221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18347221"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jongseong Kim, Cheng-Zhong Zhang, Xiaohui Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mechanically stabilized receptor-ligand flex-bond important in the vasculature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09295"}], "href": "https://doi.org/10.1038/nature09295"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20725043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20725043"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hongxia Fu, Yan Jiang, Darren Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Flow-induced elongation of von Willebrand factor precedes tension-dependent activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-00230-2"}], "href": "https://doi.org/10.1038/s41467-017-00230-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28831047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28831047"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Brian Savage, Jan J Sixma, Zaverio M Ruggeri "}, {"type": "b", "children": [{"type": "t", "text": "Functional self-association of von Willebrand factor during platelet adhesion under flow."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.012459599"}], "href": "https://doi.org/10.1073/pnas.012459599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11756664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11756664"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Koichi Kokame, Masanori Matsumoto, Yoshihiro Fujimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-08-2861"}], "href": "https://doi.org/10.1182/blood-2003-08-2861"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14512308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14512308"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Arnoldo Padilla, Joel L Moake, Aubrey Bernardo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P-selectin anchors newly released ultralarge von Willebrand factor multimers to the endothelial cell surface."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-08-2956"}], "href": "https://doi.org/10.1182/blood-2003-08-2956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14630802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14630802"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kenji Nishio, Patricia J Anderson, X Long Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Binding of platelet glycoprotein Ibalpha to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0402041101"}], "href": "https://doi.org/10.1073/pnas.0402041101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15249683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15249683"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "J E Sadler "}, {"type": "b", "children": [{"type": "t", "text": "von Willebrand factor: two sides of a coin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2005.01369.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2005.01369.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16102036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16102036"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "J A Kremer Hovinga, S Zeerleder, P Kessler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2007.02743.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2007.02743.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17764538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17764538"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Kyuhwan Shim, Patricia J Anderson, Elodee A Tuley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-05-093021"}], "href": "https://doi.org/10.1182/blood-2007-05-093021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17901248"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17901248"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Xiaohui Zhang, Kenneth Halvorsen, Cheng-Zhong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1170905"}], "href": "https://doi.org/10.1126/science.1170905"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19498171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19498171"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Junmei Chen, Xiaoyun Fu, Yi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-03-213967"}], "href": "https://doi.org/10.1182/blood-2009-03-213967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19812385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19812385"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Han-Mou Tsai "}, {"type": "b", "children": [{"type": "t", "text": "Pathophysiology of thrombotic thrombocytopenic purpura."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Hematol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12185-009-0476-1"}], "href": "https://doi.org/10.1007/s12185-009-0476-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20058209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20058209"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "James T B Crawley, Rens de Groot, Yaozu Xiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-02-306597"}], "href": "https://doi.org/10.1182/blood-2011-02-306597"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21715306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21715306"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Isabel Tirado, José Mateo, José Manuel Soria, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH04-04-0251"}], "href": "https://doi.org/10.1160/TH04-04-0251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15735796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15735796"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "A Bernardo, C Ball, L Nolasco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Platelets adhered to endothelial cell-bound ultra-large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2005.01122.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2005.01122.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15748247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15748247"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Hans Ulrichts, Miklós Udvardy, Peter J Lenting, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shielding of the A1 domain by the D'D3 domains of von Willebrand factor modulates its interaction with platelet glycoprotein Ib-IX-V."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M513314200"}], "href": "https://doi.org/10.1074/jbc.M513314200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16373331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16373331"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Paula D James, Colleen Notley, Carol Hegadorn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mutational spectrum of type 1 von Willebrand disease: Results from a Canadian cohort study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-05-021105."}], "href": "https://doi.org/10.1182/blood-2006-05-021105."}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17190853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17190853"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "S Sehgal, B Storrie "}, {"type": "b", "children": [{"type": "t", "text": "Evidence that differential packaging of the major platelet granule proteins von Willebrand factor and fibrinogen can support their differential release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2007.02698.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2007.02698.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17650077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17650077"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Veronica H Flood, Joan Cox Gill, Patricia A Morateck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-10-249102"}], "href": "https://doi.org/10.1182/blood-2009-10-249102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20231421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20231421"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Richard D Starke, Francesco Ferraro, Koralia E Paschalaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial von Willebrand factor regulates angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-01-264507"}], "href": "https://doi.org/10.1182/blood-2010-01-264507"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21048155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21048155"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Thomas D Nightingale, Ian J White, Emily L Doyle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Actomyosin II contractility expels von Willebrand factor from Weibel-Palade bodies during exocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201011119"}], "href": "https://doi.org/10.1083/jcb.201011119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21844207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21844207"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Yan-Feng Zhou, Edward T Eng, Jieqing Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequence and structure relationships within von Willebrand factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-01-405134"}], "href": "https://doi.org/10.1182/blood-2012-01-405134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22490677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22490677"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Takehiro Torisu, Kumiko Torisu, In Hye Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3288"}], "href": "https://doi.org/10.1038/nm.3288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24056772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24056772"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Sandra Grässle, Volker Huck, Karin I Pappelbaum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "von Willebrand factor directly interacts with DNA from neutrophil extracellular traps."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.113.303016"}], "href": "https://doi.org/10.1161/ATVBAHA.113.303016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24790143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24790143"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Jing-fei Dong, Joel L Moake, Aubrey Bernardo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAMTS-13 metalloprotease interacts with the endothelial cell-derived ultra-large von Willebrand factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301385200"}], "href": "https://doi.org/10.1074/jbc.M301385200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12775718"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12775718"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Anne Goodeve, Jeroen Eikenboom, Giancarlo Castaman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-05-020784"}], "href": "https://doi.org/10.1182/blood-2006-05-020784"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16985174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16985174"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Tamara N Bongers, Moniek P M de Maat, Mary-Lou P J van Goor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.STR.0000244767.39962.f7"}], "href": "https://doi.org/10.1161/01.STR.0000244767.39962.f7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16990571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16990571"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Junmei Chen, Adili Reheman, Francisca C Gushiken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI41062"}], "href": "https://doi.org/10.1172/JCI41062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21266777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21266777"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Helena M Andersson, Bob Siegerink, Brenda M Luken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-09-380618"}], "href": "https://doi.org/10.1182/blood-2011-09-380618"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22110247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22110247"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Marie Levade, Elodie David, Cédric Garcia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2014-06-583294"}], "href": "https://doi.org/10.1182/blood-2014-06-583294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25305202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25305202"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Steven W Pipe, Robert R Montgomery, Kathleen P Pratt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2016-04-713289"}], "href": "https://doi.org/10.1182/blood-2016-04-713289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27587878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27587878"}]}]}]}