{"doi":"10.1182/blood.2020007364","title":"Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice","abstract":"Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through intraperitoneal injection or IV infusion reduced TBI-induced death by >50% and significantly improved the neurological function of C57BL/6J male mice subjected to severe lateral fluid percussion injury. A2 protected the endothelium from extracellular vesicle-induced injury, reducing TBI-induced platelet activation and microvesiculation, and preventing a TBI-induced hypercoagulable state. A2 achieved this therapeutic efficacy by specifically blocking the A1 domain exposed on the hyperadhesive VWF released during acute TBI. These results suggest that VWF plays a causal role in the development of TBI-IC and is a therapeutic target for this life-threatening complication of TBI.","journal":"Blood","year":2020,"id":66876,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":354138,"name":"Chenyu Wang","orcid":"0000-0003-1808-361X","position":1,"is_corresponding":false},{"id":354985,"name":"Yingang Wu","orcid":null,"position":2,"is_corresponding":false},{"id":354986,"name":"Katie Houck","orcid":null,"position":3,"is_corresponding":false},{"id":354987,"name":"Tristan Hilton","orcid":null,"position":4,"is_corresponding":false},{"id":243057,"name":"Ashley Zhou","orcid":"0000-0002-3678-1166","position":5,"is_corresponding":false},{"id":354139,"name":"Xiaoping Wu","orcid":"0000-0003-2747-3185","position":6,"is_corresponding":false},{"id":354140,"name":"Cha Han","orcid":"0000-0001-7191-1563","position":7,"is_corresponding":false},{"id":124025,"name":"Mengchen Yang","orcid":null,"position":8,"is_corresponding":false},{"id":354141,"name":"Wei Yang","orcid":"0000-0001-8687-6473","position":9,"is_corresponding":false},{"id":354142,"name":"Fu‐Dong Shi","orcid":"0000-0002-9675-4637","position":10,"is_corresponding":false},{"id":354143,"name":"Moritz Stolla","orcid":"0000-0002-2866-1674","position":11,"is_corresponding":false},{"id":276983,"name":"Miguel A. Crúz","orcid":"0000-0002-4417-0648","position":12,"is_corresponding":false},{"id":354144,"name":"Min Li","orcid":"0000-0002-7113-2700","position":13,"is_corresponding":false},{"id":354145,"name":"Jianning Zhang","orcid":"0000-0001-5216-1496","position":14,"is_corresponding":false},{"id":332085,"name":"Jing‐fei Dong","orcid":"0000-0001-6379-4133","position":15,"is_corresponding":false},{"id":354137,"name":"Xin Xu","orcid":"0000-0003-3395-9923","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T21:14:50.590588Z","pmid":"33507292","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}