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.
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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 |
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