{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:31:29Z","timestamp":1791657089177,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009009","name":"Novartis Pharmaceuticals Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Early intervention in the devastating process of haemophilic arthropathy (HA) is highly desirable, but no disease\u2010modifying therapy is currently available. Considering the pivotal role of iron in the development of HA, iron chelation is considered a promising therapeutic approach. A previous study in haemophilic mice demonstrated that treatment with the iron chelator deferasirox (DFX) 8\u00a0weeks before joint bleed induction, attenuated cartilage damage upon blood exposure. However, in haemophilia patients this approach is not opportune given the unpredictable occurrence of hemarthroses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the effectiveness of on\u2010demand DFX treatment, initiated immediately after joint bleed induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A joint bleed was induced in 66 factor VIII\u2010deficient mice by infra\u2010patellar needle puncture. Mice were randomly assigned to treatment with either placebo (drinking water) or DFX (dissolved in drinking water) throughout the study. Five weeks after joint bleed induction, inflammation and cartilage damage were assessed histologically. Joints of ten bleed naive haemophilic mice served as controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A joint bleed resulted in significant inflammation and cartilage damage in the blood\u2010exposed joint compared with those of control animals, in both the placebo and DFX group (all <jats:italic>p<\/jats:italic>\u00a0=\u00a0&lt;.05). No differences in tibiofemoral or patellar inflammation (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.305 and <jats:italic>p<\/jats:italic>\u00a0=\u00a0.787, respectively) nor cartilage damage (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.265 and <jats:italic>p<\/jats:italic>\u00a0=\u00a0.802, respectively) were found between the blood\u2010exposed joints of both treatment groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>On\u2010demand treatment with DFX does not prevent joint damage following blood exposure in haemophilic mice. DFX seems unable to reach the joint in time to exert its effect before the irreversible harmful process is initiated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14328","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T16:56:28Z","timestamp":1622134588000},"page":"648-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["On\u2010demand treatment with the iron chelator deferasirox is ineffective in preventing blood\u2010induced joint damage in haemophilic mice"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8464-4775","authenticated-orcid":false,"given":"Astrid E.","family":"Pulles","sequence":"first","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht Utrecht University Utrecht The Netherlands"},{"name":"Van Creveldkliniek University Medical Center Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-5524","authenticated-orcid":false,"given":"Lize F. 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G.","family":"Schutgens","sequence":"additional","affiliation":[{"name":"Van Creveldkliniek University Medical Center Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris P. J. G.","family":"Lafeber","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology University Medical Center Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01732.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.11.032"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.45.1.21"},{"issue":"2","key":"e_1_2_9_6_1","first-page":"339","article-title":"Blood\u2010induced joint damage: longterm effects in vitro and in vivo","volume":"30","author":"Hooiveld M","year":"2003","journal-title":"J Rheumatol"},{"issue":"2","key":"e_1_2_9_7_1","first-page":"275","article-title":"Ultrastructural appearance of human synovial membrane in the reabsorption phase of acute haemarthrosis","volume":"6","author":"Letizia G","year":"1980","journal-title":"Ital J Orthop Traumatol"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00976.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03962.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.80B3.0800540"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keg220"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/32.7.562"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2011.569493"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004967"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/tcrm.2007.3.2.291"},{"issue":"5","key":"e_1_2_9_16_1","first-page":"1044","article-title":"Deferasirox limits cartilage damage following haemarthrosis in haemophilic mice","volume":"112","author":"Nieuwenhuizen L","year":"2014","journal-title":"Thromb Haemost"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12950"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13969"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01689.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00899.x"},{"key":"e_1_2_9_21_1","first-page":"483","volume-title":"The Merck Index \u2010 An Encyclopedia of Chemicals, Drugs, and Biologicals","author":"O'Neil MJ","year":"2006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3181\/0811-RM-337"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13778"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12399"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2008.03.017"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-734053"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key186"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13672"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01348.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.1999.00863.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.030833"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22304"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-217455"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780240609"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-009-0885-x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.016824"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.178"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12101"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.120370"},{"key":"e_1_2_9_40_1","unstructured":"Agency EM.European public assessment report on Exjade Annex I \u2010 Summary of product characteristics.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/exjade\u2010epar\u2010product\u2010information_en.pdf. 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