{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:36:16Z","timestamp":1791657376026,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T00:00:00Z","timestamp":1444262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Biogen for \u201cprevalence and etiology of subclinical joint bleeding and \u2018joint microbleeding\u2019 in adults with hemophilic arthropathy\u201d"},{"name":"An Early Career Development Award from Bayer Hemophilia"},{"name":"A Novo Nordisk Career Development Award from the National Hemophilia Foundation"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL091385"],"award-info":[{"award-number":["HL091385"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA94233"],"award-info":[{"award-number":["CA94233"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA192658"],"award-info":[{"award-number":["CA192658"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL104165"],"award-info":[{"award-number":["HL104165"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII\u2010deficient mouse. We found soft\u2010tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft\u2010tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII\u2010deficient mice involved pronounced remodeling with expression of \u03b1\u2010Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of \u03b1\u2010SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease. Am. J. Hematol. 90:1027\u20131035, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24133","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T23:28:07Z","timestamp":1438990087000},"page":"1027-1035","source":"Crossref","is-referenced-by-count":96,"title":["Vascular remodeling underlies rebleeding in hemophilic arthropathy"],"prefix":"10.1002","volume":"90","author":[{"given":"Vikas","family":"Bhat","sequence":"first","affiliation":[{"name":"Department of Molecular and Experimental Medicine The Scripps Research Institute La Jolla California"},{"name":"Department of Medicine University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merissa","family":"Olmer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine The Scripps Research Institute La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California San Diego  California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Durden","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California San Diego  California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard FW","family":"Barnes","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Ball","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor H.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Radiology University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Silva","sequence":"additional","affiliation":[{"name":"Orthopedic Institute for Children University of California Los Angeles Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James V.","family":"Luck","sequence":"additional","affiliation":[{"name":"Orthopedic Institute for Children University of California Los Angeles Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy E.","family":"Moore","sequence":"additional","affiliation":[{"name":"General Musculoskeletal Imaging Inc Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent O.","family":"Mosnier","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine The Scripps Research Institute La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"von Drygalski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine The Scripps Research Institute La Jolla California"},{"name":"Department of Medicine University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61139-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1457"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12267"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1994.tb00815.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12539"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-470898"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0455.2002.430514.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12878-015-0022-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02001.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02847.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12637"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-050435"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03962.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0390"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-12-4231"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.80B3.0800540"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12101"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-284653"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01689.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.301082"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-058-8_11"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27305"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1532-2149.2013.00358.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01348.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1078\/0344-0338-5710261"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e31829433b6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.083915"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-11-0874"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.60.7.641"},{"key":"e_1_2_8_34_1","first-page":"2485","article-title":"Musculoskeletal ultrasound including definitions for ultrasonographic pathology","volume":"32","author":"Wakefield RJ","year":"2005","journal-title":"J Rheumatol"},{"key":"e_1_2_8_35_1","first-page":"153","article-title":"A radiologic classification of hemophilic arthropathy","author":"Pettersson H","year":"1980","journal-title":"Clin Orthop Relat Res"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01750.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24646"},{"key":"e_1_2_8_38_1","doi-asserted-by":"crossref","DOI":"10.1002\/0471722146","volume-title":"Applied Logistic Regression","author":"Hosmer DaL S.","year":"2000"},{"key":"e_1_2_8_39_1","volume-title":"Applied Regression Analysis and Other Multivariable Methods","author":"Kleinbaum D","year":"2008"},{"key":"e_1_2_8_40_1","first-page":"277","article-title":"Vasculature of the normal and arthritic synovial joint","volume":"16","author":"Haywood L","year":"2001","journal-title":"Histol Histopathol"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02380.x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12175"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.231548"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.02.004"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00378.2006"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1681"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22238"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.100614"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01732.x"},{"key":"e_1_2_8_50_1","first-page":"339","article-title":"Blood\u2010induced joint damage: Long term effects in vitro and in vivo","volume":"30","author":"Hooiveld M","year":"2003","journal-title":"J Rheumatol"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63889-8"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2005.01080.x"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12176"},{"key":"e_1_2_8_54_1","first-page":"680","article-title":"Effects of weekly blood collection in C57BL\/6 mice","volume":"50","author":"Raabe BM","year":"2011","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009749850154429"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4431"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200109)44:9<2055::AID-ART355>3.0.CO;2-2"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01973.x"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200102)44:2<331::AID-ANR50>3.0.CO;2-0"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2251011272"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.05.025"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu354"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0716-97602012000300008"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1452"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.109"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem284"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12056"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.24133","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.24133","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.24133","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T06:37:11Z","timestamp":1695537431000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.24133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,8]]},"references-count":66,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1002\/ajh.24133"],"URL":"https:\/\/doi.org\/10.1002\/ajh.24133","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,8]]}}}