{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:23:56Z","timestamp":1792232636586,"version":"4.4.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,3,20]]},"abstract":"<jats:p>Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor\u2013treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.<\/jats:p>","DOI":"10.1084\/jem.20052458","type":"journal-article","created":{"date-parts":[[2006,3,13]],"date-time":"2006-03-13T20:34:14Z","timestamp":1142282054000},"page":"513-518","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":399,"title":["Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis"],"prefix":"10.1084","volume":"203","author":[{"given":"Christoph","family":"Kleinschnitz","sequence":"first","affiliation":[{"name":"1Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Stoll","sequence":"additional","affiliation":[{"name":"1Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bendszus","sequence":"additional","affiliation":[{"name":"2Department of Neuroradiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Schuh","sequence":"additional","affiliation":[{"name":"3Institute for Clinical Biochemistry and Pathobiochemistry, University of Wu\u0308rzburg, 97080 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Ulrich","family":"Pauer","sequence":"additional","affiliation":[{"name":"4Department of Gynecology and Obstetrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Burfeind","sequence":"additional","affiliation":[{"name":"5Institute of Human Genetics, University of Go\u0308ttingen, 37073 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Renne\u0301","sequence":"additional","affiliation":[{"name":"6Institute for Pathology, University of Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gailani","sequence":"additional","affiliation":[{"name":"7Departments of Pathology and"},{"name":"8Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Nieswandt","sequence":"additional","affiliation":[{"name":"3Institute for Clinical Biochemistry and Pathobiochemistry, University of Wu\u0308rzburg, 97080 Wu\u0308rzburg, Germany"},{"name":"9Rudolf Virchow Center, 97078 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Renne\u0301","sequence":"additional","affiliation":[{"name":"3Institute for Clinical Biochemistry and Pathobiochemistry, University of Wu\u0308rzburg, 97080 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,3,13]]},"reference":[{"key":"2023072513311612200_BIB1","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0140-6736(96)07493-4","volume":"349","year":"1997","journal-title":"Lancet."},{"key":"2023072513311612200_BIB2","volume":"3","year":"2004","journal-title":"Cochrane Database Syst. Rev."},{"key":"2023072513311612200_BIB3","doi-asserted-by":"crossref","first-page":"108S","DOI":"10.1378\/chest.119.1_suppl.108S","volume":"119","year":"2001","journal-title":"Chest."},{"key":"2023072513311612200_BIB4","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1126\/science.145.3638.1310","volume":"145","year":"1964","journal-title":"Science."},{"key":"2023072513311612200_BIB5","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/202498a0","volume":"202","year":"1964","journal-title":"Nature."},{"key":"2023072513311612200_BIB6","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1161\/01.ATV.0000130465.23430.74","volume":"24","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2023072513311612200_BIB7","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/36862","volume":"390","year":"1997","journal-title":"Nature."},{"key":"2023072513311612200_BIB8","doi-asserted-by":"crossref","first-page":"6258","DOI":"10.1073\/pnas.93.13.6258","volume":"93","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072513311612200_BIB9","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1172\/JCI103109","volume":"34","year":"1955","journal-title":"J. Clin. Invest."},{"key":"2023072513311612200_BIB10","year":"2001"},{"key":"2023072513311612200_BIB11","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1126\/science.1652157","volume":"253","year":"1991","journal-title":"Science."},{"key":"2023072513311612200_BIB12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1084\/jem.20050664","volume":"202","year":"2005","journal-title":"J. Exp. Med."},{"key":"2023072513311612200_BIB13","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1172\/JCI3338","volume":"102","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2023072513311612200_BIB14","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1097\/01.WCB.0000078322.96027.78","volume":"23","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2023072513311612200_BIB15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/107602960501100105","volume":"11","year":"2005","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"2023072513311612200_BIB16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1056\/NEJM199107183250303","volume":"325","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"2023072513311612200_BIB17","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1182\/blood-2003-01-0324","volume":"102","year":"2003","journal-title":"Blood."},{"key":"2023072513311612200_BIB18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1172\/JCI781","volume":"101","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2023072513311612200_BIB19","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1073\/pnas.74.12.5260","volume":"74","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072513311612200_BIB20","doi-asserted-by":"crossref","first-page":"11563","DOI":"10.1073\/pnas.94.21.11563","volume":"94","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072513311612200_BIB21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1084\/jem.190.1.91","volume":"190","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072513311612200_BIB22","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1126\/science.6648524","volume":"222","year":"1983","journal-title":"Science."},{"key":"2023072513311612200_BIB23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1126\/science.285.5427.595","volume":"285","year":"1999","journal-title":"Science."},{"key":"2023072513311612200_BIB24","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/sj.jcbfm.9600096","volume":"25","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2023072513311612200_BIB25","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/j.1432-1033.1987.tb11174.x","volume":"164","year":"1987","journal-title":"Eur. J. Biochem."},{"key":"2023072513311612200_BIB26","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1172\/JCI110898","volume":"71","year":"1983","journal-title":"J. Clin. Invest."},{"key":"2023072513311612200_BIB27","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/01616412.1997.11740874","volume":"19","year":"1997","journal-title":"Neurol. Res."},{"key":"2023072513311612200_BIB28","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/jcbfm.1990.47","volume":"10","year":"1990","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2023072513311612200_BIB29","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1161\/01.STR.17.3.472","volume":"17","year":"1986","journal-title":"Stroke."},{"key":"2023072513311612200_BIB30","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1073\/pnas.92.12.5341","volume":"92","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/203\/3\/513\/1720151\/513.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/203\/3\/513\/1720151\/513.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T09:32:06Z","timestamp":1690277526000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/203\/3\/513\/53980\/Targeting-coagulation-factor-XII-provides"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,13]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,3,20]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20052458","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2006,3,13]]}}}