Iron studies

Components of iron studies

Ferritin is the storage form of iron. It is an acute phase protein so can be falsely elevated or normal.

Transferrin is the main iron transport protein. It increases to maximise use of iron and decreases if iron overload.

Serum iron is the level of iron bound to transferrin. Levels are highly variable.

Transferrin saturation is the proportion of transferrin occupied by iron. High TSAT is good to pickup iron overload but low is not particularly sensitive to iron deficiency as things such as pregnancy, OCP use and chronic illness can lower TSAT even in the absence of iron deficiency.

Practicalities for requesting iron studies

  • Do a fasting morning sample – serum iron has diurnal variation and may rise with food ingestion
  • Do not test during acute illness
  • Do not assume microcytic anaemias are IDA – check ferritin levels
    • Low ferritin is diagnostic of IDA (but a normal/high does not exclude IDA)

Causes of raised ferritin

  • 90% are reactive
    • Liver disease
    • Alcohol excess
    • Inflammatory disorders
    • Malignancy

< 10% are due to iron overload

Indications for iron studies

  • Iron overload (haemochromatosis)
    • can be asymptomatic in early presentation
    • presentation: lethargy, joint pains, deranged liver enzymes, erectile dysfunction, cardiomyopathy
  • Iron deficiency
    • investigating cause of anaemia
    • iron malabsorption – unintentional weight loss, chronic diarrhoea, coeliac disease
    • distinguishing low iron stores from functional iron deficiency e.g. CKD
  • Response to medical treatment
    • monitoring patients requiring repeated transfusions or venesection
    • assessing response to iron therapy
    • assessing response to iron chelators


  • Iron deficiency
    • Reduced: Ferritin, Iron, Transferrin saturation
    • Increased: Transferrin/TIBC, Unsaturated iron binding capacity
    • Can be normal: Transferrin/TIBC
  • Anaemia of chronic disease/Inflammatory response
    • Reduced: Iron, Transferrin/TIBC, Unsaturated iron binding capacity, Transferrin saturation
    • Increased: Ferritin
    • Can be normal: Unsaturated iron binding capacity
  • Haemochromatosis with iron overload
    • Reduced: Transferrin/TIBC, Unsaturated iron binding capacity
    • Increased: Ferritin, Iron, Transferrin saturation
  • Secondary iron overload (repeated transfusions)
    • Reduced/Normal: Transferrin/TIBC, Unsaturated iron binding capacity
    • Increased: Ferritin, Iron, Transferrin saturation
  • Iron poisoning
    • Reduced: Unsaturated iron binding capacity
    • Increased: Iron, Transferrin saturation
    • Normal: Ferritin, Transferrin/TIBC

Components of an iron study

  • Ferritin
    • Intracellular storage form of iron
    • Acute phase protein – rises in inflammation, liver disease, malignancy (and hence can mask low iron stores)
  • Serum iron
    • Ferric ions (Fe3+) bound to serum transferrin
    • Concentration is highly variable and affected by dietary iron intake, inflammation and infection
  • Transferrin
    • Main iron transport protein in plasma
    • Increases in iron deficiency to maximise utilisation of available iron
  • Total Iron Binding Capacity (TIBC)
    • Alternative test to Transferrin. Reflects the availability of iron binding sites on transferrin
  • Transferrin saturation
    • Typically, transferrin is 30% saturated with iron
    • Rises with iron overload
    • Falls with iron deficiency
    • Does not quantitatively reflect iron stores


  • Elevated transferrin saturation in isolation
    • repeat on a fasting sample to ensure diet is not the cause
    • if persistently raised, offer HFE gene analysis (after pre-test counselling)
    • ensure not taking oral iron supplements
  • Acute hepatic injury
    • can cause high ferritin, iron, transferrin and transferrin saturation and can incorrect appear as iron overload