{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T12:04:25Z","timestamp":1770552265494,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T00:00:00Z","timestamp":1445472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Fonds Nuts Ohra, the Netherlands"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Sickle cell disease (<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (<jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content>s) on magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>). Both local vaso\u2010occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (<jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>) have been proposed to be involved in the aetiology. We performed an explorative study to investigate the associations between <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content>s and markers of endothelial dysfunction and <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content> by quantifying <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content> volume on 3\u00b70\u00a0Tesla <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>. We included 40 children with Hb<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content> or HbS\u03b2<jats:sup>0<\/jats:sup>thalassaemia, with a mean age of 12\u00b71\u00a0\u00b1\u00a02\u00b76\u00a0years. Boys demonstrated an increased risk for <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content>s (odds ratio 4\u00b75, 95% confidence interval 1\u00b72\u201317\u00b74), unrelated to glucose\u20106\u2010phosphate dehydrogenase deficiency. In patients with <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content>s, lower fetal haemoglobin (HbF) was associated with a larger <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content> volume (regression coefficient\u00a0=\u00a0\u22120\u00b762, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00\u00b725, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b704). Lower <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels were associated with lower <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content> in the white matter (regression coefficient\u00a0=\u00a00\u00b707, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00\u00b715, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b703), suggesting that endothelial dysfunction could potentially hamper <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>. The findings of our explorative study suggest that a high level of HbF may be protective for <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content>s and that endothelial dysfunction may contribute to the development of <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content>s by reducing <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.13819","type":"journal-article","created":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T13:38:04Z","timestamp":1445607484000},"page":"274-284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease"],"prefix":"10.1111","volume":"172","author":[{"given":"Veronica","family":"van der Land","sequence":"first","affiliation":[{"name":"Department of Paediatric Haematology, Immunology and Infectious Diseases Emma Children's Hospital Academic Medical Centre Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri J. 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M.","family":"Mutsaerts","sequence":"additional","affiliation":[{"name":"Department of Radiology Academic Medical Centre Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Engelen","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Emma Children's Hospital Academic Medical Centre Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harri\u00ebt","family":"Heijboer","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology, Immunology and Infectious Diseases Emma Children's Hospital Academic Medical Centre Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Roest","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Haematology University Medical Centre Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine J.","family":"Hollestelle","sequence":"additional","affiliation":[{"name":"Department Immunopathology and Blood Coagulation Sanquin Diagnostic Services Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taco W.","family":"Kuijpers","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology, Immunology and Infectious Diseases Emma Children's Hospital Academic Medical Centre Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul. 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