{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:46:34Z","timestamp":1792111594938,"version":"4.4.0"},"reference-count":65,"publisher":"Georg Thieme Verlag KG","issue":"02","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The prevalence of factor XI (FXI) deficiency is 1 per 10 to 20,000 in the general population, much higher than that reported in most texts. The prevalence is higher in Ashkenazi Jews where it is about 1:20. Clinically, FXI deficiency presents as a mild bleeding disorder mostly associated with posttraumatic or postsurgical hemorrhages or unexplained minor bleeding. It is often discovered due to incidental finding of a prolonged activated partial thromboplastin time (aPTT) on routine laboratory screening. FXI deficiency is an autosomal recessive bleeding disorder with many causative F11 gene defects. Diagnosis is based on FXI activity, antigen levels, and molecular diagnostics. As FXI levels do not correlate with bleeding symptoms, identification of pathogenic genetic variants may be a more accurate predictor of bleeding risk and therefore aid in the clinical management of the patient. Two variants in the F11 gene account for most cases found in the Jewish and Arab populations. Patients with FXI deficiency can develop inhibitors to FXI although spontaneously acquired inhibitors are extremely rare. We will discuss laboratory and molecular assays used to diagnose FXI deficiency as well as interferences that can complicate diagnosis including new anticoagulants and acquired FXI inhibitors.<\/jats:p>","DOI":"10.1055\/s-0044-1792033","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:40:32Z","timestamp":1730767232000},"page":"145-154","source":"Crossref","is-referenced-by-count":8,"title":["Laboratory and Molecular Diagnosis of Factor XI Deficiency"],"prefix":"10.1055","volume":"51","author":[{"given":"Simon","family":"Davidson","sequence":"additional","affiliation":[{"name":"Division of Medicine, Faculty of Medical Sciences, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Gomez","sequence":"additional","affiliation":[{"name":"Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"issue":"06","key":"ref1","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.hoc.2021.07.012","article-title":"Factor XI deficiency","volume":"35","author":"M D Lewandowska","year":"2021","journal-title":"Hematol Oncol Clin North Am"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1056\/NEJM199107183250303","article-title":"Factor XI deficiency in Ashkenazi Jews in Israel","volume":"325","author":"R Asakai","year":"1991","journal-title":"N Engl J Med"},{"issue":"07","key":"ref3","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1182\/blood.V90.7.2654","article-title":"The two common mutations causing factor XI deficiency in Jews stem from distinct founders: one of ancient Middle Eastern origin and another of more recent European origin","volume":"90","author":"H Peretz","year":"1997","journal-title":"Blood"},{"issue":"02","key":"ref6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/hae.12856","article-title":"Gynaecological and obstetrical bleeding in women with factor XI deficiency - 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Murray","year":"2022","journal-title":"Hematol Transfus Cell Ther"},{"issue":"03","key":"ref46","doi-asserted-by":"crossref","first-page":"e233","DOI":"10.1055\/s-0040-1714696","article-title":"Acquired factor XI deficiency during SARS-CoV-2 infection: not only thrombosis","volume":"4","author":"G Andreani","year":"2020","journal-title":"TH Open"},{"issue":"01","key":"ref47","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/j.1365-2516.2011.02553.x","article-title":"Approach to the treatment, characterization and diagnosis of an acquired auto-antibody directed against factors prothrombin, factor X and factor IX: a case report and review of the literature","volume":"18","author":"L Rochanda","year":"2012","journal-title":"Haemophilia"},{"issue":"02","key":"ref48","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/ejh.13249","article-title":"A very potent factor V inhibitor interferes with the levels of all coagulation factors and causes a fatal hemorrhagic 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Berber","year":"2011","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1111\/hae.15081","article-title":"Diagnosis and management of factor XI alloinhibitors in patients with congenital factor XI deficiency-A large single-centre experience","author":"K S Kamel","year":"2024","journal-title":"Haemophilia"},{"issue":"02","key":"ref59","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1182\/blood.V85.2.429.429","article-title":"One of the two common mutations causing factor XI deficiency in Ashkenazi Jews (type II) is also prevalent in Iraqi Jews, who represent the ancient gene pool of Jews","volume":"85","author":"O Shpilberg","year":"1995","journal-title":"Blood"},{"issue":"07","key":"ref60","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1182\/blood.V99.7.2448","article-title":"Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI 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