{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:16:54Z","timestamp":1790644614617,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T00:00:00Z","timestamp":1590192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Subclinical synovitis occur long before clinical haemophilic arthropathy (HA). New biomarkers are needed for early detection of HA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare the levels of tissue inhibitors of metalloproteinase\u20101 (TIMP\u20101) and vascular endothelial growth factor (VEGF)in severe haemophilia A boys on prophylaxis and on\u2010demand therapy to healthy boys and correlate them with the haemophilia joint health score (HJHS) &amp; the Denver magnetic resonance imaging (MRI) scale; hence, determine their values in early detection of HA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Haemophilia joint health score, serum TIMP\u20101, VEGF and Denver MRI score were assessed in 50 boys with severe haemophilia A (31 on prophylactic factor VIII therapy (62%) with a dose of 15\u00a0IU\/kg\/twice weekly) and 50 age\u2010matched healthy boys.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Boys with severe haemophilia A had significantly higher TIMP\u20101 240\u00a0ng\/mL, SD200\u2010350 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and VEGF 600\u00a0pg\/mL, SD400\u20101100 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Their mean HJHS was 4.5\u00a0\u00b1\u00a03.0 (0\u201011) and their mean Denver MRI score was 5.55\u00a0\u00b1\u00a01.6 (2.00\u20108.00). A significant positive correlation was found between TIMP\u20101 and VEGF (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), BMI <jats:italic>Z<\/jats:italic>\u2010score (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.029), HJHS (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.041)and total MRI score (&lt;.001). Significant correlations were found between VEGF and age (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), HJHS (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.003) and total MRI score (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Boys with severe haemophilia A on prophylaxis therapy had significantly lower HJHS (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.021), VEGF (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), TIMP\u20101 (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.002) and total MRI score (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.021) than those on on\u2010demand therapy. Receiver operating characteristic curve, defined a cut\u2010off value of 160\u00a0ng\/mL for TIMP\u20101 with a sensitivity of 90% and specificity of 60% and that of 350\u00a0pg\/mL for VEGF with a sensitivity of 78% and specificity of 88% for discrimination between severe haemophilia A and healthy boys.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Vascular endothelial growth factor and TIMP\u20101 can be used for early detection of HA. Further prospective studies should include larger study populations. In addition, studies should address the role of various anti\u2010VEGFs as potential therapy for HA and their impact on prevention and treatment of HA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14041","type":"journal-article","created":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T13:25:05Z","timestamp":1590240305000},"page":"607-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tissue\u2010inhibitors of metalloproteinase\u20101 and vascular\u2010endothelial growth\u2010factor in severe haemophilia A children on low dose prophylactic recombinant factor VIII: Relation to subclinical arthropathy"],"prefix":"10.1111","volume":"26","author":[{"given":"Nevine Gamal","family":"Andrawes","sequence":"first","affiliation":[{"name":"Pediatric Department Faculty of Medicine Ain\u2010Shams University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam Mousa","family":"Saker","sequence":"additional","affiliation":[{"name":"Radiology Department Faculty of Medicine Ain\u2010Shams University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6507-8835","authenticated-orcid":false,"given":"Nouran Yousef","family":"Salah El\u2010Din","sequence":"additional","affiliation":[{"name":"Pediatric Department Faculty of Medicine Ain\u2010Shams University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervat","family":"Abd Elhakim Hussain","sequence":"additional","affiliation":[{"name":"Pediatric Department Sheikh Zayed hospital Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17040492"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6070063"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24133"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001238"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2015.10.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.5152\/eurjrheum.2019.19040"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12936"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2017.11.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-665091"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-014-3112-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12227"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/S136898001200105X"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01312.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2000.00383.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2020.1685867"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-1923-x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029619828113"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12101"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-284653"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/9781681083537117020004"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13417-w"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.14041","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14041","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.14041","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T05:34:46Z","timestamp":1693719286000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.14041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,23]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/hae.14041"],"URL":"https:\/\/doi.org\/10.1111\/hae.14041","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,23]]},"assertion":[{"value":"2020-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}