{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:24:18Z","timestamp":1747146258513,"version":"3.40.5"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"LIFEHARM - University of Copenhagen"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent degree of histopathological changes and the development of bone pathology in a mouse model of hemophilic arthropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>FVIII knock\u2010out (F8\u2010KO) mice were dosed with a micro\u2010CT blood pool agent prior to induction of hemarthrosis. Eight hours after induction, the bleed volume was quantified with micro computed tomography (micro\u2010CT) and recombinant FVIII treatment initiated. On Day 8, inflammation in the knees was characterized by fluorescence molecular tomography. On Day 14, knee pathology was characterized by micro\u2010CT and histopathology. In a second study, contrast agent was injected into the knee of wild\u2010type (WT)\u00a0mice, followed by histopathological evaluation on Day 14.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The average joint bleed volume before treatment was 3.9\u00a0mm<jats:sup>3<\/jats:sup>. The inflammation\u2010related fluorescent intensities in the injured knees were significantly increased on Day 8. The injured knees had significantly increased synovitis scores, vessel counts, and areas of hemosiderin compared to un\u2010injured knees. However, no cartilage\u2010 or bone pathology was observed. The bleed volume before initiation of treatment correlated with the degree of synovitis and was associated with high fluorescent intensity on Day 8. In F8\u2010KO and WT mice, persistence of contrast agent in the joint elicited morphological changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>When applying a delayed on\u2010demand treatment regimen to hemophilic mice subjected to an induced knee hemarthrosis, the degree of histopathological changes on Day 14 reflected the bleed volume prior to initiation of treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12118","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T13:15:53Z","timestamp":1591190153000},"page":"160-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Initial joint bleed volume in a delayed on\u2010demand treatment setup correlates with subsequent synovial changes in hemophilic mice"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6701-2087","authenticated-orcid":false,"given":"K\u00e5re 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