{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:20:05Z","timestamp":1787761205128,"version":"build-2784847793"},"reference-count":46,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Blood Vessels, Thrombosis &amp; Hemostasis"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.bvth.2026.100182","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:15:22Z","timestamp":1781907322000},"page":"100182","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired cellular trafficking of a thrombomodulin mutant causes severe bleeding, thrombosis, and atypical hemolytic uremic syndrome"],"prefix":"10.1016","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8652-6414","authenticated-orcid":false,"given":"Joanna","family":"Gemel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-0926","authenticated-orcid":false,"given":"Zhour","family":"Barnawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Dahlgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-5510","authenticated-orcid":false,"given":"Anthony","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shireen","family":"Hashmat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-4904","authenticated-orcid":false,"given":"Jordan A.","family":"Shavit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6185-1605","authenticated-orcid":false,"given":"Gabrielle","family":"Lapping-Carr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-1356","authenticated-orcid":false,"given":"Eric C.","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10","key":"10.1016\/j.bvth.2026.100182_bib1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1182\/blood-2017-04-636431","article-title":"Pathophysiology of thrombotic thrombocytopenic purpura","volume":"130","author":"Sadler","year":"2017","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.bvth.2026.100182_bib2","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/bjh.19026","article-title":"A British Society for Haematology Guideline: diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies","volume":"203","author":"Scully","year":"2023","journal-title":"Br J Haematol"},{"issue":"15","key":"10.1016\/j.bvth.2026.100182_bib3","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1056\/NEJMra2108739","article-title":"Shiga toxin-producing Escherichia coli and the hemolytic-uremic syndrome","volume":"389","author":"Freedman","year":"2023","journal-title":"N Engl J Med"},{"issue":"6","key":"10.1016\/j.bvth.2026.100182_bib4","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.semnephrol.2013.08.003","article-title":"Atypical hemolytic uremic syndrome","volume":"33","author":"Kavanagh","year":"2013","journal-title":"Semin Nephrol"},{"issue":"2","key":"10.1016\/j.bvth.2026.100182_bib5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5551\/jat.RV17026","article-title":"Pathogenesis of atypical hemolytic uremic syndrome","volume":"26","author":"Yoshida","year":"2019","journal-title":"J Atheroscler Thromb"},{"key":"10.1016\/j.bvth.2026.100182_bib6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jim.2018.07.006","article-title":"Atypical hemolytic uremic syndrome: review of clinical presentation, diagnosis and management","volume":"461","author":"Sridharan","year":"2018","journal-title":"J Immunol Methods"},{"issue":"10","key":"10.1016\/j.bvth.2026.100182_bib7","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2215\/CJN.02210310","article-title":"Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype","volume":"5","author":"Noris","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"issue":"4","key":"10.1016\/j.bvth.2026.100182_bib8","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1182\/blood-2005-10-007252","article-title":"Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome","volume":"108","author":"Caprioli","year":"2006","journal-title":"Blood"},{"issue":"16","key":"10.1016\/j.bvth.2026.100182_bib9","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1182\/blood.2022018833","article-title":"Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study","volume":"142","author":"Brocklebank","year":"2023","journal-title":"Blood"},{"key":"10.1016\/j.bvth.2026.100182_bib10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-1-4939-3628-1_4","article-title":"Isolation and culture of human endothelial cells from micro- and macro-vessels","volume":"1430","author":"Hewett","year":"2016","journal-title":"Methods Mol Biol"},{"issue":"23","key":"10.1016\/j.bvth.2026.100182_bib11","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21238884","article-title":"Gap junctions between endothelial cells are disrupted by circulating extracellular vesicles from sickle cell patients with acute chest syndrome","volume":"21","author":"Gemel","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"3","key":"10.1016\/j.bvth.2026.100182_bib12","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11030816","article-title":"Circulating small extracellular vesicles may contribute to vaso-occlusive crises in sickle cell disease","volume":"11","author":"Gemel","year":"2022","journal-title":"J Clin Med"},{"issue":"1-2","key":"10.1016\/j.bvth.2026.100182_bib13","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal Biochem"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1242\/dev.059345","article-title":"Ubiquitous transgene expression and Cre-based recombination driven by the ubiquitin promoter in zebrafish","volume":"138","author":"Mosimann","year":"2011","journal-title":"Development"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.devcel.2004.06.005","article-title":"A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish","volume":"7","author":"Kawakami","year":"2004","journal-title":"Dev Cell"},{"key":"10.1016\/j.bvth.2026.100182_bib16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/B978-0-12-387036-0.00009-8","article-title":"Laser-induced thrombosis in zebrafish","volume":"101","author":"Jagadeeswaran","year":"2011","journal-title":"Methods Cell Biol"},{"key":"10.1016\/j.bvth.2026.100182_bib17","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/bs.mcb.2016.01.003","article-title":"Quantitative methods for studying hemostasis in zebrafish larvae","volume":"134","author":"Rost","year":"2016","journal-title":"Methods Cell Biol"},{"issue":"2","key":"10.1016\/j.bvth.2026.100182_bib18","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1182\/blood.V75.2.329.329","article-title":"Structure and function of thrombomodulin: a natural anticoagulant","volume":"75","author":"Dittman","year":"1990","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib19","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1055\/s-0038-1657558","article-title":"Thrombomodulin structure and function","volume":"78","author":"Sadler","year":"1997","journal-title":"Thromb Haemost"},{"issue":"7","key":"10.1016\/j.bvth.2026.100182_bib20","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1046\/j.1538-7836.2003.00306.x","article-title":"Thrombomodulin","volume":"1","author":"Weiler","year":"2003","journal-title":"J Thromb Haemost"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib21","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1182\/blood-2014-03-561027","article-title":"Targeted mutagenesis of zebrafish antithrombin III triggers disseminated intravascular coagulation and thrombosis, revealing insight into function","volume":"124","author":"Liu","year":"2014","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.bvth.2026.100182_bib22","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1182\/bloodadvances.2024013237","article-title":"Loss of protein C vs protein S results in discrepant thrombotic phenotypes","volume":"9","author":"Ku","year":"2025","journal-title":"Blood Adv"},{"issue":"9","key":"10.1016\/j.bvth.2026.100182_bib23","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1016\/S0021-9258(18)83649-3","article-title":"The roles of protein C and thrombomodulin in the regulation of blood coagulation","volume":"264","author":"Esmon","year":"1989","journal-title":"J Biol Chem"},{"issue":"9","key":"10.1016\/j.bvth.2026.100182_bib24","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1161\/hq0901.094496","article-title":"Characterization of a mouse model for thrombomodulin deficiency","volume":"21","author":"Weiler","year":"2001","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"24","key":"10.1016\/j.bvth.2026.100182_bib25","doi-asserted-by":"crossref","first-page":"14477","DOI":"10.1074\/jbc.270.24.14477","article-title":"Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor","volume":"270","author":"Bajzar","year":"1995","journal-title":"J Biol Chem"},{"issue":"7","key":"10.1016\/j.bvth.2026.100182_bib26","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1172\/JCI925","article-title":"Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity","volume":"101","author":"Zhang","year":"1998","journal-title":"J Clin Invest"},{"issue":"2","key":"10.1016\/j.bvth.2026.100182_bib27","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1182\/blood-2017-12-768994","article-title":"Exploring traditional and nontraditional roles for thrombomodulin","volume":"132","author":"Loghmani","year":"2018","journal-title":"Blood"},{"issue":"2","key":"10.1016\/j.bvth.2026.100182_bib28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1348-0421.2002.tb02669.x","article-title":"Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N","volume":"46","author":"Campbell","year":"2002","journal-title":"Microbiol Immunol"},{"issue":"8","key":"10.1016\/j.bvth.2026.100182_bib29","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1161\/01.ATV.0000134298.25489.92","article-title":"Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation","volume":"24","author":"Van de Wouwer","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"2","key":"10.1016\/j.bvth.2026.100182_bib30","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1161\/ATVBAHA.123.320000","article-title":"Thrombomodulin regulates PTEN\/AKT signaling axis in endothelial cells","volume":"44","author":"Giri","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib31","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1055\/s-0038-1657559","article-title":"Thrombomodulin gene variations and thromboembolic disease","volume":"78","author":"Ohlin","year":"1997","journal-title":"Thromb Haemost"},{"issue":"4","key":"10.1016\/j.bvth.2026.100182_bib32","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1161\/01.ATV.19.4.1098","article-title":"Mutations in promoter region of thrombomodulin and venous thromboembolic disease","volume":"19","author":"Le Flem","year":"1999","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"10","key":"10.1016\/j.bvth.2026.100182_bib33","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.1182\/blood.V99.10.3646","article-title":"Naturally occurring mutations in the thrombomodulin gene leading to impaired expression and function","volume":"99","author":"Kunz","year":"2002","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1161\/01.CIR.96.1.15","article-title":"Thrombomodulin gene mutations associated with myocardial infarction","volume":"96","author":"Ireland","year":"1997","journal-title":"Circulation"},{"issue":"4","key":"10.1016\/j.bvth.2026.100182_bib35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1056\/NEJMoa0810739","article-title":"Thrombomodulin mutations in atypical hemolytic-uremic syndrome","volume":"361","author":"Delvaeye","year":"2009","journal-title":"N Engl J Med"},{"issue":"9","key":"10.1016\/j.bvth.2026.100182_bib37","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1182\/blood-2014-10-604553","article-title":"Characterization of an autosomal dominant bleeding disorder caused by a thrombomodulin mutation","volume":"125","author":"Dargaud","year":"2015","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.bvth.2026.100182_bib38","first-page":"467","article-title":"Mouse models of thrombosis: thrombomodulin","volume":"92","author":"Weiler","year":"2004","journal-title":"Thromb Haemost"},{"issue":"13","key":"10.1016\/j.bvth.2026.100182_bib39","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1182\/bloodadvances.2024013143","article-title":"Loss of factor VIII in zebrafish rebalances antithrombin deficiency but has a limited bleeding diathesis","volume":"9","author":"Raghunath","year":"2025","journal-title":"Blood Adv"},{"issue":"4","key":"10.1016\/j.bvth.2026.100182_bib40","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/jth.14391","article-title":"Loss of fibrinogen in zebrafish results in an asymptomatic embryonic hemostatic defect and synthetic lethality with thrombocytopenia","volume":"17","author":"Hu","year":"2019","journal-title":"J Thromb Haemost"},{"issue":"5","key":"10.1016\/j.bvth.2026.100182_bib41","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1182\/blood-2017-02-765206","article-title":"Genome editing of factor X in zebrafish reveals unexpected tolerance of severe defects in the common pathway","volume":"130","author":"Hu","year":"2017","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib42","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.1038\/s41598-020-60840-7","article-title":"Disruption of the kringle 1 domain of prothrombin leads to late onset mortality in zebrafish","volume":"10","author":"Grzegorski","year":"2020","journal-title":"Sci Rep"},{"issue":"19","key":"10.1016\/j.bvth.2026.100182_bib36","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1182\/bloodadvances.2020003814","article-title":"A novel homozygous variant of the thrombomodulin gene causes a hereditary bleeding disorder","volume":"5","author":"Osada","year":"2021","journal-title":"Blood Adv"},{"issue":"12","key":"10.1016\/j.bvth.2026.100182_bib44","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1182\/bloodadvances.2019001155","article-title":"A case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation","volume":"4","author":"Okada","year":"2020","journal-title":"Blood Adv"},{"issue":"23","key":"10.1016\/j.bvth.2026.100182_bib45","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1056\/NEJMoa1208981","article-title":"Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome","volume":"368","author":"Legendre","year":"2013","journal-title":"N Engl J Med"},{"issue":"4","key":"10.1016\/j.bvth.2026.100182_bib46","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/jth.12841","article-title":"Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis","volume":"13","author":"Yamakawa","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"1","key":"10.1016\/j.bvth.2026.100182_bib47","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1055\/s-0038-1676345","article-title":"Recombinant human soluble thrombomodulin in sepsis-induced coagulopathy: an updated systematic review and meta-analysis","volume":"119","author":"Yamakawa","year":"2019","journal-title":"Thromb Haemost"}],"container-title":["Blood Vessels, Thrombosis &amp; Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2950327226000471?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2950327226000471?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:27:00Z","timestamp":1787758020000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2950327226000471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S2950327226000471"],"URL":"https:\/\/doi.org\/10.1016\/j.bvth.2026.100182","relation":{},"ISSN":["2950-3272"],"issn-type":[{"value":"2950-3272","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Impaired cellular trafficking of a thrombomodulin mutant causes severe bleeding, thrombosis, and atypical hemolytic uremic syndrome","name":"articletitle","label":"Article Title"},{"value":"Blood Vessels, Thrombosis & Hemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bvth.2026.100182","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"100182"}}