{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:18:51Z","timestamp":1785313131279,"version":"3.55.0"},"reference-count":38,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81570178"],"award-info":[{"award-number":["81570178"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81700130"],"award-info":[{"award-number":["81700130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81970112"],"award-info":[{"award-number":["81970112"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81670127"],"award-info":[{"award-number":["81670127"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81270594"],"award-info":[{"award-number":["81270594"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Municipal Health Commission in China","award":["201940342"],"award-info":[{"award-number":["201940342"]}]},{"name":"Novo Nordisk Haemophilia Research Fund in China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Platelet-targeted FVIII gene therapy can efficiently recover bleeding phenotype for hemophilia A (HA), yet characteristics of thrombus formation with this ectopic expression of factor VIII (FVIII) in platelets remain unclear. Here, we generated 2bF8trans mice restrictively expressing human B-domain\u2013deleted FVIII (hBDD FVIII) in platelets on a hemophilic (FVIIInull) mice background. The results showed no statistical difference in clot strength and stability between wild-type (WT) and 2bF8trans mice, but with a prolonged reaction time (R-time), by thromboelastography. Fluid dynamics analysis showed that at the shear rates of 500 to 1,500\u2009s\u22121, where physiological hemostasis often develops, the thrombi formed in 2bF8trans mice were more stable than those in FVIIInull mice, while at high pathological shear rates (2,500\u2009s\u22121), mimicking atherosclerosis, thrombus size and fibrin deposition in 2bF8trans mice were less than those in WT mice. Thrombus morphology analysis showed that there was a locally concentrated deposition of fibrin in thrombus at the injured site and fibrin co-localized with activated platelets in 2bF8trans mice. Moreover, a higher ratio of fibrin to platelets was found in thrombus from 2bF8trans mice following laser-induced injury in cremaster arterioles, which might be the underlying mechanism of thrombus stability in 2bF8trans mice at physiological arterial circumstance. These observations suggest that specific morphological features of the thrombi might contribute to the efficacy and safety of platelet-targeted FVIII gene therapy for HA.<\/jats:p>","DOI":"10.1055\/s-0041-1735531","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T22:57:48Z","timestamp":1632956268000},"page":"755-766","source":"Crossref","is-referenced-by-count":2,"title":["Characteristics of the Thrombus Formation in Transgenic Mice with Platelet-Targeted Factor VIII Expression"],"prefix":"10.1055","volume":"122","author":[{"given":"Yun","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Mao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"},{"name":"Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Ruan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Department of Basic Medical Sciences, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1556-1594","authenticated-orcid":false,"given":"Dawei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Qing","family":"Mi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Xi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China"},{"name":"Department of Hematology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, P\u00f4le Sino-Fran\u00e7ais des Sciences du Vivant et Genomique, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1111\/j.1365-2516.2012.02909.x","article-title":"Guidelines for the management of hemophilia","volume":"19","author":"A Srivastava","year":"2013","journal-title":"Haemophilia"},{"key":"ref2","first-page":"s126","article-title":"Economic costs of hemophilia and the impact of prophylactic treatment on patient management","volume":"22","author":"S L Chen","year":"2016","journal-title":"Am J Manag 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Hematol"},{"issue":"01","key":"ref25","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1182\/blood-2010-07-299057","article-title":"An accompanying genetic severe deficiency of tissue factor protects mice with a protein C deficiency from lethal endotoxemia","volume":"117","author":"F J Castellino","year":"2011","journal-title":"Blood"},{"issue":"04","key":"ref26","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1182\/blood.V80.4.988.988","article-title":"Shear rate-dependent impairment of thrombus growth on collagen in nonanticoagulated blood from patients with von Willebrand disease and hemophilia A","volume":"80","author":"E Fressinaud","year":"1992","journal-title":"Blood"},{"issue":"06","key":"ref27","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1073\/pnas.1813642116","article-title":"Interrelationships between structure and function during the hemostatic response to injury","volume":"116","author":"M Tomaiuolo","year":"2019","journal-title":"Proc 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The interdependence of thrombus architecture and agonist movements in the gaps between platelets","volume":"124","author":"J D Welsh","year":"2014","journal-title":"Blood"},{"issue":"10","key":"ref30","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.3324\/haematol.2019.235754","article-title":"Shear rate gradients promote a bi-phasic thrombus formation on weak adhesive proteins, such as fibrinogen in a VWF-dependent manner","volume":"105","author":"N Receveur","year":"2020","journal-title":"Haematologica"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1146\/annurev-bioeng-071516-044539","article-title":"Thrombus formation at high shear rates","volume":"19","author":"L DC Casa","year":"2017","journal-title":"Annu Rev Biomed Eng"},{"issue":"04","key":"ref32","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.jvs.2014.12.050","article-title":"Role of high shear rate in thrombosis","volume":"61","author":"L D Casa","year":"2015","journal-title":"J Vasc Surg"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"e82493","DOI":"10.1371\/journal.pone.0082493","article-title":"Microfluidic thrombosis under multiple shear rates and antiplatelet therapy doses","volume":"9","author":"M Li","year":"2014","journal-title":"PLoS One"},{"issue":"05","key":"ref34","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1055\/s-0040-1709524","article-title":"Platelet activation via shear stress exposure induces a differing pattern of biomarkers of activation versus biochemical agonists","volume":"120","author":"Y Roka-Moiia","year":"2020","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref35","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1182\/blood.V88.5.1525.1525","article-title":"Platelets and shear stress","volume":"88","author":"M H Kroll","year":"1996","journal-title":"Blood"},{"issue":"03","key":"ref36","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/10739680490425949","article-title":"Mouse cremaster venules are predisposed to light\/dye-induced thrombosis independent of wall shear rate, CD18, ICAM-1, or P-selectin","volume":"11","author":"R E Rumbaut","year":"2004","journal-title":"Microcirculation"},{"issue":"115","key":"ref37","first-page":"e54479","article-title":"Ferric chloride-induced murine thrombosis models","volume":"5","author":"W Li","year":"2016","journal-title":"J Vis Exp"},{"issue":"02","key":"ref38","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.bpj.2020.10.049","article-title":"Modeling thrombus shell: linking adhesion receptor properties and macroscopic dynamics","volume":"120","author":"V N Kaneva","year":"2021","journal-title":"Biophys J"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1735531.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T18:21:50Z","timestamp":1699554110000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1735531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":38,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2022,6,14]]},"published-print":{"date-parts":[[2022,5]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1735531","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]}}}