Iron overload across the spectrum of non‐transfusion‐dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions

• Published in: British journal of haematology Vol. 176; no. 2; pp. 288 - 299
• Main Authors: Porter, John B., Cappellini, Maria Domenica, Kattamis, Antonis, Viprakasit, Vip, Musallam, Khaled M., Zhu, Zewen, Taher, Ali T.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2017; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Aged; anaemia; Biomarkers; Biomarkers - blood; Blood diseases; Blood Transfusion; Child; Double-Blind Method; Erythroblasts - pathology; Erythrocytes; Erythropoiesis; Female; Ferritin; Ferritins - blood; Growth Differentiation Factor 15 - blood; Hematology; Hemoglobin; Hepcidin; Hepcidins - blood; Humans; ineffective erythropoiesis; Iron; Iron - blood; Iron - metabolism; iron overload; Iron Overload - etiology; Liver; Liver - metabolism; Male; Metabolism; Middle Aged; non‐transfusion‐dependent thalassaemia; Receptors, Transferrin - blood; Red Cells and Iron; Research Paper; Saturation; Splenectomy; Thalassemia - blood; Thalassemia - complications; Thalassemia - therapy; Transferrin - metabolism; Transferrins; Transfusion; Young Adult; iron overload; ineffective erythropoiesis; anaemia; non-transfusion-dependent thalassaemia
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.14373

Summary 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%.