UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The Pathophysiology of Transfusional Iron Overload

Porter, JB; Garbowski, M; (2014) The Pathophysiology of Transfusional Iron Overload. Hematology/Oncology Clinics of North America , 28 (4) pp. 683-701. 10.1016/j.hoc.2014.04.003. Green open access

[thumbnail of Porter and Garbowski 2014.pdf]
Preview
Text
Porter and Garbowski 2014.pdf - Accepted Version

Download (522kB) | Preview

Abstract

The pathophysiological consequences of transfusional iron overload (TIO) as well as the benefits of iron chelation are best described in Thalassemia Major (TM), although TIO is increasingly seen in other clinical settings. These consequences broadly reflect the levels and distribution of excess storage iron in the heart, endocrine tissues and liver. MRI-visible storage iron does not directly damage cells, but its intracellular turnover contributes to labile iron pools that generate harmful free radicals. TIO also increases the risk of infection, due to increased availability of labile iron to microorganisms. Although storage iron accumulates firstly and predominantly in the liver, heart failure from myocardial iron loading typically precedes the hepatic complications of cirrhosis and hepatocellular carcinoma by at least two decades. With improved chelation, decreased cardiomyopathy and increasing survival, hepatic complications are more commonly encountered. Storage iron distribution reflects the pattern of transferrin-independent iron uptake (NTBI), which in animal models has been linked to L-type calcium channels. The propensity of iron overload to distribute extra-hepatically differs between underlying clinical conditions. Thus Sickle Cell Disease (SCD) patients have a lower risk of myocardial and endocrine iron deposition than TM and also have disproportionately low NTBI levels. Conversely, DiamondBlackfan Anemia (DBA) patients are prone to extra-hepatic iron deposition, and have high levels of NTBI, consistent with low transferrin iron utilization. We suggest that extra-hepatic iron distribution, and hence toxicity, is influenced by balance between generation of NTBI from red cell catabolism and the utilization of transferrin iron by the erythron.

Type: Article
Title: The Pathophysiology of Transfusional Iron Overload
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.hoc.2014.04.003
Publisher version: https://doi.org/10.1016/j.hoc.2014.04.003
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Iron overload, Pathophysiology, Mechanism, Thalassemia, Sickle cell disease, Blood transfusion, NTBIExtra-hepatic iron distribution
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10072254
Downloads since deposit
228Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item