title: Iron overload across the spectrum of non-transfusion-dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions.
abstract: Non-transfusion-dependent thalassaemias (NTDT) 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 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non-splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor-15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra-hepatic iron distribution are more likely in previously transfused, splenectomised and iron-overloaded NTDT patients with TfSat >70%.
authors.affiliation: University College London, London, UK.
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.affiliation: Università di Milano, Ca Granda Foundation IRCCS, Milan, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.affiliation: First Department of Pediatrics, University of Athens, Athens, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
authors.affiliation: Department of Pediatrics and Thalassemia Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Musallam
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: Zewen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Ali T
authors.initials: AT
authors.lastname: Taher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001803:Blood Transfusion; D002648:Child; D004311:Double-Blind Method; D004900:Erythroblasts / Q000473:pathology; D004920:Erythropoiesis; D005260:Female; D005293:Ferritins / Q000097:blood; D055436:Growth Differentiation Factor 15 / Q000097:blood; D064451:Hepcidins / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism; D019190:Iron Overload / Q000209:etiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000097:blood; D013156:Splenectomy; D013789:Thalassemia / Q000097:blood / Q000150:complications* / Q000628:therapy; D014168:Transferrin / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D064451:Hepcidins; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins; D007501:Iron
keywords: anaemia; ineffective erythropoiesis; iron overload; non-transfusion-dependent thalassaemia