{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:24:50Z","timestamp":1790645090693,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T00:00:00Z","timestamp":1480896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Non\u2010transfusion\u2010dependent thalassaemias (<jats:styled-content style=\"fixed-case\">NTDT<\/jats:styled-content>) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 <jats:styled-content style=\"fixed-case\">NTDT<\/jats:styled-content> patients with \u03b2 thalassaemia intermedia (<jats:italic>n<\/jats:italic>\u00a0=\u00a095), haemoglobin (Hb) E\/\u03b2 thalassaemia (<jats:italic>n<\/jats:italic>\u00a0=\u00a049) and Hb H syndromes (<jats:italic>n<\/jats:italic>\u00a0=\u00a022). Liver iron concentration (<jats:styled-content style=\"fixed-case\">LIC<\/jats:styled-content>), serum ferritin (<jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>), transferrin saturation (TfSat) and non\u2010transferrin\u2010bound iron (<jats:styled-content style=\"fixed-case\">NTBI<\/jats:styled-content>) were elevated and correlated across diagnostic subgroups. <jats:styled-content style=\"fixed-case\">NTBI<\/jats:styled-content> correlated with soluble transferrin receptor (<jats:styled-content style=\"fixed-case\">sTfR<\/jats:styled-content>), labile plasma iron (<jats:styled-content style=\"fixed-case\">LPI<\/jats:styled-content>) and nucleated red blood cells (<jats:styled-content style=\"fixed-case\">NRBC<\/jats:styled-content>s), with elevations generally confined to previously transfused patients. Splenectomised patients had higher <jats:styled-content style=\"fixed-case\">NTBI<\/jats:styled-content>, TfSat, <jats:styled-content style=\"fixed-case\">NRBC<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content> relative to <jats:styled-content style=\"fixed-case\">LIC<\/jats:styled-content>, than non\u2010splenectomised patients. <jats:styled-content style=\"fixed-case\">LPI<\/jats:styled-content> elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (<jats:styled-content style=\"fixed-case\">sTfR<\/jats:styled-content>, growth differentiation factor\u201015, <jats:styled-content style=\"fixed-case\">NRBC<\/jats:styled-content>s) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with &gt;20 prior transfusions, and correlated inversely with TfSat, <jats:styled-content style=\"fixed-case\">NTBI<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> LPI<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NRBC<\/jats:styled-content>s. Hepcidin\/<jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content> ratios were low, consistent with hepcidin suppression relative to iron overload. Increased <jats:styled-content style=\"fixed-case\">NTBI<\/jats:styled-content> and, by implication, risk of extra\u2010hepatic iron distribution are more likely in previously transfused, splenectomised and iron\u2010overloaded <jats:styled-content style=\"fixed-case\">NTDT<\/jats:styled-content> patients with TfSat &gt;70%.<\/jats:p>","DOI":"10.1111\/bjh.14373","type":"journal-article","created":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T06:49:21Z","timestamp":1480920561000},"page":"288-299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Iron overload across the spectrum of non\u2010transfusion\u2010dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions"],"prefix":"10.1111","volume":"176","author":[{"given":"John B.","family":"Porter","sequence":"first","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Domenica","family":"Cappellini","sequence":"additional","affiliation":[{"name":"Universit\u00e0 di Milano Ca Granda Foundation IRCCS Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Kattamis","sequence":"additional","affiliation":[{"name":"First Department of Pediatrics University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vip","family":"Viprakasit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Thalassemia Center Siriraj Hospital Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled M.","family":"Musallam","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zewen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali T.","family":"Taher","sequence":"additional","affiliation":[{"name":"American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,12,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.4033"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112125"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2004.10.003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3468"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0807"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1182\/asheducation-2009.1.26","article-title":"Hb H disease: clinical course and disease modifiers","author":"Fucharoen S.","year":"2009","journal-title":"Hematology the Education Program of the American Society of Hematology"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011734"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-11"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.2.561.561"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2010.08.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-13"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2996"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010174"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2012.10.006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80240-8"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.047852"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a013482"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2013.01.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.097220"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703424104"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.10842"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21275"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-471441"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)92175-5"},{"key":"e_1_2_9_26_1","first-page":"3","article-title":"Iron metabolism in thalassemia","volume":"23","author":"Pootrakul P.","year":"1988","journal-title":"Birth Defects Original Article Series"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13081"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67396-5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.9.3199"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-011-1385-y"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-01-0177"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.13098"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07848.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07810.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08486.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-412692"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13119"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/358283"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1629"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1182\/asheducation-2007.1.79","article-title":"Hemoglobin E syndromes","author":"Vichinsky E.","year":"2007","journal-title":"Hematology\/the Education Program of the American Society of Hematology"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011742"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11755"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(12)70003-6"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0560083"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.14373","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.14373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T05:32:37Z","timestamp":1694323957000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.14373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,5]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1111\/bjh.14373"],"URL":"https:\/\/doi.org\/10.1111\/bjh.14373","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,5]]},"assertion":[{"value":"2016-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-12-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}