Iron Overload

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Iron overload occurs when excess iron accumulates in the body. Those receiving iron therapy are vulnerable to iron overload as we lack major mechanisms for iron excretion (minor ones are cell desquamation and occult blood loss). Excess iron is deposited in body organs (the heart, liver and endocrine glands in particular), causing organ damage. Probably, iron saturates the liver first and then accumulates in other organs[1].

Hereditary haemochromatosis

This is a genetic condition where individuals show increased iron absorption and organ deposition. There are various types, including the HFE gene mutations, which are relatively common in Northern European populations.

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Repeated red blood cell transfusions

Iron excess can occur from as little as 10 transfusions. It is a common problem in transfusion-dependent patients - for example, those with thalassaemia major, sickle cell disease and myelodysplastic syndromes[3]. Beta thalassaemia major patients may have the greatest iron overload because their iron absorption is also increased[1].

Other causes of iron overload

  • Liver disease.
  • Excessive iron intake or supplementation.
  • Porphyria cutanea tarda.
  • Aceruloplasminaemia (rare).
  • Usually there are no symptoms until organ damage (possibly irreversible) has occurred. Therefore, awareness and monitoring of those at risk are important.
  • Early symptoms of hereditary haemochromatosis include fatigue and arthritis (often arthritis of the hands, particularly the index and middle fingers)[4].
  • In patients with thalassaemia, cardiac iron overload may present as reduced exercise tolerance or with features of right-sided heart failure.
  • It may present as an incidental finding - eg, unexplained raised serum ferritin levels or unexplained liver disease may trigger investigation for haemochromatosis.

Identifying the cause

This may be known - eg, multiple transfusions. See also separate Hereditary Haemochromatosis article, which details investigation of suspected hereditary haemochromatosis.

Guidelines for the investigation of people with suspected hereditary haemochromatosis can also be found in the European Association for the Study of the Liver Clinical Practice Guidelines for HFE Hemochromatosis (April 2010)[5].

Assessment of iron load[1]

  • Ferritin levels give an indication of body iron stores. However, they are also affected by other conditions (ferritin is an acute-phase protein), so trends are more important than individual measurements[6].
  • Liver iron may be assessed by:
    • MRI scan, either with the R2 (Ferriscan®) method, or using the T2* (pronounced "T2-star") technique.
    • Liver biopsy (invasive).
  • Cardiac investigations:
    • T2* MRI scan is a useful technique for evaluating cardiac iron overload. It is important because cardiac iron load does not always correlate with liver iron or ferritin levels. Measurement of cardiac iron enables appropriate adjustment of chelation treatment, which should help to prevent cardiac complications.
    • Echocardiography (echo) and electrocardiography (ECG) - to monitor cardiac function and detect complications early.
    • Where MRI is not available, monitor ferritin levels, liver iron status, echo and ECG carefully.

Hereditary haemochromatosis can be treated by venesection to remove iron. In those with refractory anaemias where repeated venesection is not an option, iron chelation can be used. Chelating agents form chelator-iron complexes which are then safely excreted in urine or stools.

Chelation treatment should normally be managed by a consultant haematologist with experience in this field.

Chelation drugs

Iron chelators currently used are desferrioxamine, deferiprone and desferasirox[7]:

  • Desferrioxamine has been important first-line treatment for chronic iron overload over a period of 30 years. It is usually given subcutaneously over 8-12 hours, 3-7 times a week, often with a pump at night. It has led to significant life expectancy gains for those with conditions such as thalassaemia major[3]. However, the infusion regime is demanding and so compliance can be difficult.
  • Deferiprone and deferasirox are newer, oral chelators with slightly different chelating properties[8]. Compared with desferrioxamine, deferiprone is more efficient in removing cardiac iron. Less is known about the effect of deferasirox on cardiac iron[1].
  • New strategies have emerged involving combination therapy. Using desferrioxamine and deferiprone together has advantages above monotherapy - eg, in reducing cardiac iron load[9, 10].
  • Cardiac disease:
    • Cardiac failure:
      • In thalassaemia, it tends to present with gradually reduced physical activity and features of right ventricular dysfunction - eg, fatigue and abdominal pain[1].
    • Arrhythmias.
    • Pericarditis.
  • Liver damage.
  • Endocrine disorders, including diabetes.
  • Infections - Yersinia spp. and Klebsiella spp.

The prognosis depends on the underlying condition and the degree of iron overload - for example:

  • For thalassaemia major (one of the most severe forms of iron overload):
    • Without chelation, the iron overload causes death in the teenage years or 20s.
    • With chelation treatment, life expectancy is vastly improved. With optimal treatment, heart failure usually presents in the 30s or 40s[1].
    • Recent developments in chelation may improve the prognosis.
  • For hereditary haemochromatosis:
    • Early treatment can confer normal life expectancy.
    • Untreated patients tend to develop complications during their 40s (with a wide age range).

Some complications can be reversed - for example:

  • Recent experience with thalassaemia patients found that intensive chelation can in some cases reduce cardiac iron overload and may even completely remove it, together with resolution of heart failure[1].
  • Some complications of hereditary haemochromatosis are reversible after venesection treatment[4].

Further reading & references

  • McLeod C, Fleeman N, Kirkham J, et al; Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation. Health Technol Assess. 2009 Jan;13(1):iii-iv, ix-xi, 1-121.
  • Wood MJ, Skoien R, Powell LW; The global burden of iron overload. Hepatol Int. 2009 Jul 29.
  • Toliyat T, Jorjani M, Khorasanirad Z; An extended-release formulation of desferrioxamine for subcutaneous administration. Drug Deliv. 2009 Jul 30.
  1. Aessopos A, Berdoukas V, Tsironi M; The heart in transfusion dependent homozygous thalassaemia today--prediction, prevention and management. Eur J Haematol. 2008 Feb;80(2):93-106. Epub 2007 Dec 10.
  2. Kohgo Y, Ikuta K, Ohtake T, et al; Body iron metabolism and pathophysiology of iron overload. Int J Hematol. 2008 Jul;88(1):7-15. doi: 10.1007/s12185-008-0120-5. Epub 2008 Jul 2.
  3. Roberts DJ, Rees D, Howard J, et al; Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004450.
  4. The Haemochromatosis Society
  5. Management of HFE Hemochromatosis; European Association for the Study of the Liver (April 2010)
  6. Vermylen C; What is new in iron overload? Eur J Pediatr. 2008 Apr;167(4):377-81. Epub 2007 Sep 26.
  7. British National Formulary; NICE Evidence Services (UK access only)
  8. Neufeld EJ; Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood. 2006 May 1;107(9):3436-41.
  9. Tanner MA, Galanello R, Dessi C, et al; A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation. 2007 Apr 10;115(14):1876-84. Epub 2007 Mar 19.
  10. Daar S, Pathare AV; Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload. Ann Hematol. 2006 May;85(5):315-9. Epub 2006 Feb 1.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Chloe Borton
Current Version:
Peer Reviewer:
Dr Adrian Bonsall
Document ID:
496 (v4)
Last Checked:
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