{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:04:29Z","timestamp":1791515069513,"version":"4.3.4"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>Factor XIa is a plasma serine protease that contributes to thrombin generation primarily through proteolytic activation of factor IX. Traditionally considered part of the intrinsic pathway of coagulation, several lines of evidence now suggest that factor XIa serves as an interface between the vitamin-K\u2013dependent thrombin generation mechanism and the proinflammatory kallikrein\u2013kinin system, allowing the 2 systems to influence each other. Work with animal models and results from epidemiological surveys of human populations support a role for factor XIa in thromboembolic disease. These data and the clinical observation that deficiency of factor XI, the zymogen of factor XIa, produces a relatively mild bleeding disorder suggest that drugs targeting factor XI or XIa could produce an antithrombotic effect while leaving hemostasis largely intact. Results of a recent trial comparing antisense-induced factor XI reduction to standard-dose low molecular\u2013weight heparin as prophylaxis for venous thrombosis during knee replacement are encouraging in this regard. Here, we discuss recent findings on the biochemistry, physiology, and pathology of factor XI as they relate to thromboembolic disease.<\/jats:p>","DOI":"10.1161\/atvbaha.116.306925","type":"journal-article","created":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T03:19:59Z","timestamp":1463109599000},"page":"1316-1322","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":114,"title":["Factor XI as a Therapeutic Target"],"prefix":"10.1161","volume":"36","author":[{"given":"David","family":"Gailani","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Microbiology and Immunology and Department of Medicine, Vanderbilt University, Nashville, TN (D.G.); and Aronora, Inc, Portland, OR (A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Gruber","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Microbiology and Immunology and Department of Medicine, Vanderbilt University, Nashville, TN (D.G.); and Aronora, Inc, Portland, OR (A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-120543"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-12-4195"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.303397"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2014.1.66"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2014.1.60"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1353420"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1405760"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2009.74.001"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-199182"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13235"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13194"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152968"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01304.x"},{"key":"e_1_3_4_16_2","first-page":"159","article-title":"The role of tissue factor pathway inhibitor in a revised coagulation cascade.","volume":"29","author":"Broze GJ","year":"1992","unstructured":"Broze GJ The role of tissue factor pathway inhibitor in a revised coagulation cascade. Semin Hematol. 1992;29:159\u2013169.","journal-title":"Semin Hematol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13261"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421004"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-219915"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-05-0307"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1159\/000297966"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.943738"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-120139"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-023697"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00195.x"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01236.x"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270918"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.02.020"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0324"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-163675"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-499111"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI781"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.01034.x"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63989-2"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052458"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306954"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303209"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-386185"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0411182"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2014.1.52"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-277798"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12961"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.116.306925","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:56:32Z","timestamp":1715554592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.116.306925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1161\/ATVBAHA.116.306925"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.116.306925","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7]]},"assertion":[{"value":"2016-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}