{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:51:36Z","timestamp":1790175096748,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T00:00:00Z","timestamp":1385337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Repeated intra\u2010articular bleedings in patients with haemophilia results in a crippling arthropathy for which no specific treatment is currently available. Recent studies have shown that neoangiogenesis is involved in the pathologic process. The aim of this study was to determine whether angiogenesis is dysregulated in haemophilic joint disease (HJD<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Synovial tissue and synovial fluid were collected from patients with severe haemophilia undergoing knee or hip replacement and from a control group consisting of non\u2010haemophilic patients undergoing diagnostic procedures. In a second set of patients, blood samples were collected in patients with mild, moderate and severe haemophilia A<\/jats:styled-content> when free from current bleeding. Analysis of microvascular density, vascular endothelial growth factor (VEGF<\/jats:styled-content>) expression and pericyte coverage was performed by immunofluorescence. Analyses of VEGF<\/jats:styled-content> concentrations in plasma, platelet lysates and synovial fluid were performed by ELISA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>Microvascular density and VEGF<\/jats:styled-content> expression were significantly increased in synovial tissue from haemophilic patients compared with controls (P\u00a0<\/jats:italic>=\u00a00.005 and P\u00a0<\/jats:italic>=\u00a00.02, respectively). There was no difference in pericyte coverage of synovial vessels or levels of VEGF<\/jats:styled-content> in plasma, platelet lysates or synovial fluid.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Angiogenesis observed as synovial microvascular density, and VEGF<\/jats:styled-content> expression is increased in HJD<\/jats:styled-content>. As pericyte coverage was similar in synovial vessels from haemophilic and non\u2010haemophilic patients, we assume that the vessels were mature, suggesting that the rate of new vessel formation is low in the chronic phase of haemophilic joint disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12227","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T08:58:24Z","timestamp":1383037104000},"page":"256-262","source":"Crossref","is-referenced-by-count":34,"title":["Angiogenesis is increased in advanced haemophilic joint disease and characterised by normal pericyte coverage"],"prefix":"10.1111","volume":"92","author":[{"given":"Eva","family":"Zetterberg","sequence":"first","affiliation":[{"name":"Coagulation Unit Haematology Centre Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"},{"name":"Department of Haematology and Coagulation Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Palmblad","sequence":"additional","affiliation":[{"name":"Department of Medicine and Haematology Karolinska Institutet Karolinska University Hospital Huddinge Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rickard","family":"Wallensten","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Morfini","sequence":"additional","affiliation":[{"name":"Agency for Haemophilia Department of Emergency & Reception Azienda Ospedaliero\u2010Universitaria Careggi Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Melchiorre","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine Division of Rheumatology University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Holmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Coagulation Unit Haematology Centre Karolinska University Hospital and Karolinska Institutet Stockholm 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