{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:07:33Z","timestamp":1783548453497,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>In patients with an increased bleeding tendency, extensive diagnostic blood testing is often performed. When results of tier 1 assays of primary haemostasis are normal, protocols recommend additional testing to rule out rare disorders including coagulation factor XIII (FXIII) and \u03b12\u2010antiplasmin (\u03b12AP) deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the added diagnostic value of FXIII and \u03b12AP levels in patients with a bleeding disorder of unknown cause (BDUC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective monocentre cohort study between August 2011 and August 2023 was conducted. In all patients with bleeding tendencies and normal diagnostic tests for von Willebrand disease and platelet function, FXIII and \u03b12AP were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 158 consecutive patients; mean ISTH\u2010BAT scores were 8.2 (SD\u00a0\u00b1\u00a03.7) in children, 6.2 (SD\u00a0\u00b1\u00a02.1) in men and 10.6 (SD\u00a0\u00b1\u00a03.3) in women. Median age was 37 (range 5\u201379) years, 88.6% of patients were female. Patients displayed median FXIII activity of 111% (IQR\u00a0=\u00a097\u2013131) and median \u03b12AP activity of 112% (IQR\u00a0=\u00a0103\u2013119).<\/jats:p><jats:p>Three (1.9%) patients had FXIII levels\u00a0&lt;\u00a050%, respectively 43%, 45% and 46%. Corresponding ISTH\u2010BAT scores were 7, 12 and 14. No \u03b12AP levels\u00a0&lt;\u00a060% was observed. No significant association was found between FXIII levels and ISTH\u2010BAT scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In our cohort of BDUC patients, no clinical relevant FXIII deficiencies were detected; absolute values were well above the 30% cutoff considered adequate for normal haemostasis. No \u03b12AP deficiencies were detected. These data suggest that in BDUC patients, measuring FXIII or AP activity is of limited value.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.15059","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T05:04:02Z","timestamp":1717045442000},"page":"998-1002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Limited value of testing for factor XIII and \u03b12\u2010antiplasmin deficiency in patients with a bleeding disorder of unknown cause"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9675-122X","authenticated-orcid":false,"given":"Sander","family":"Ari\u00ebns","sequence":"first","affiliation":[{"name":"Center for Benign Haematology Thrombosis and Haemostasis, van Creveldkliniek  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Huisman","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory University Medical Center Utrecht and University Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-0429","authenticated-orcid":false,"given":"Idske C. L. Kremer","family":"Hovinga","sequence":"additional","affiliation":[{"name":"Center for Benign Haematology Thrombosis and Haemostasis, van Creveldkliniek  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf T.","family":"Urbanus","sequence":"additional","affiliation":[{"name":"Center for Benign Haematology Thrombosis and Haemostasis, van Creveldkliniek  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3251-8595","authenticated-orcid":false,"given":"Karin P. M.","family":"van Galen","sequence":"additional","affiliation":[{"name":"Center for Benign Haematology Thrombosis and Haemostasis, van Creveldkliniek  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-5524","authenticated-orcid":false,"given":"Lize F. D.","family":"van Vulpen","sequence":"additional","affiliation":[{"name":"Center for Benign Haematology Thrombosis and Haemostasis, van Creveldkliniek  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-6613","authenticated-orcid":false,"given":"Kathelijn","family":"Fischer","sequence":"additional","affiliation":[{"name":"Center for Benign Haematology Thrombosis and Haemostasis, van Creveldkliniek  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2762-6033","authenticated-orcid":false,"given":"Roger E. G.","family":"Schutgens","sequence":"additional","affiliation":[{"name":"Center for Benign Haematology Thrombosis and Haemostasis, van Creveldkliniek  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"150","article-title":"Verbetering van de diagnostiek en behandelin van personen met een onverklaarde bloedingsneiging in Nederland","volume":"20","author":"Monard A","year":"2023","journal-title":"NTVH"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020010038"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13058"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2021.07.009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102516.2008.01857.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2012.04653.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537\u20102995.2012.03865.x"},{"key":"e_1_2_9_9_1","unstructured":"Foundation NBD.Factor XIII: An overview of symptoms genetics and treatments to help you understand factor XIII deficiency: NBDF."},{"key":"e_1_2_9_10_1","unstructured":"Medscape. Alpha2\u2010Plasmin Inhibitor Deficiency.2022."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049\u20103848(96)00059\u2010x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102141.2001.02845.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102516.2008.01766.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12231"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2022.11.045"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13422"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.15059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T18:08:41Z","timestamp":1744567721000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.15059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,29]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/hae.15059"],"URL":"https:\/\/doi.org\/10.1111\/hae.15059","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,29]]},"assertion":[{"value":"2024-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}