Iron Studies
 

Iron Overload

 
 
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Overview

  • Iron overload refers to an excess of total body iron stores. This may be due to haemochromatosis, or one of several secondary causes.

Aetiology

    • Causes of Iron Overload

    • Haemochromatosis
    • Iron loading anaemias - thalassaemias, sideroblastic anaemia, congenital dyserythropoietic anaemia
    • Multiple blood transfusions
    • Excessive iron administration
  • Hereditary haemochromatosis is the classic cause of iron overload, with the potential for iron deposition in major organs including the skin, liver, pancreas and heart. The main gene defect causing haemochromatosis is mutation of the C282Y HFE gene (type I haemochromatosis). Other genes defects that cause haemochromatosis are haemojuvelin (IIa), hepcidin (IIb), transferrin receptor 2 (III) and ferroportin 1 (IV).
  • Frequent blood transfusion can result in iron overload, as one unit of packed red blood cells contains approximately 250mg of iron. Overload can also be caused by excessive iron administration; this is mainly through parenteral means as oral intake is unlikely to be sufficient to cause significantly elevated stores.
  • Iron loading anaemias such as sideroblastic anaemia, thalassaemia and congenital dyserythropoietic anaemia tend to cause significant anaemia with clinical iron overload, even in the absence of frequent blood transfusions.

Manifestations

    • Clinical Features of Iron Overload

    • History

    • Fatigue
    • Cardiac involvement - palpitations, exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, peripheral oedema
    • Hepatic involvement - jaundice, ascites, haematemesis, malaena, confusion
    • Endocrine involvement - diabetes mellitus, evidence of hypopituitarism or hypogonadism
    • Joint involvement - arthralgias
    • Examination

    • Bronze discolouration of skin
    • Hepatomegaly
    • Signs of heart failure - raised JVP, displaced apex beat, third heart sound, murmurs, crepitations, ascites, pedal oedema
    • Signs of decompensated liver disease - jaundice, leukonychia, palmar erythema, spider naevi, gynaecomastia, caput medusae, ascites, splenomegaly

Diagnosis

    • Markers of Iron Overload

    • Elevated ferritin
    • Elevated transferrin saturation
  • Elevated ferritin is a key marker of iron overload. Ferritin is also an acute phase reactant, and as such an isolated elevation of ferritin is not necessarily an indicator of iron overload. Ferritin levels >200 ug/L in premenopausal women or >300 ug/L in men and postmenopausal women are concerning for true iron overload.
  • Transferrin saturations >50% in women or >60% in men are indicative of iron overload.
 
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