Greater Glasgow and Clyde Medicines

Diagnosis of IDA - Iron Studies

The GGC guideline on the Treatment of Iron Deficiency Anaemia (IDA) has been updated and is available on StaffNet here. An abbreviated version of this guideline is also available in the Therapeutics Handbook here.

In order to ensure iron is prescribed appropriately, the following information on the diagnosis of IDA should be considered. If haemoglobin is low (anaemia), blood iron studies can identify if this is caused by iron deficiency.

Key messages:

  • Serum ferritin (SF) is the most useful test for iron deficiency.
  • Serum iron, transferrin levels and transferrin saturation (TSAT) are labile measurements and not reliable indicators of low iron stores. Their role should be limited to investigation of high SF values and possible iron overload.
  • Low SF (<15micrograms/L) provides absolute evidence of iron deficiency.
  • Ferritin levels can be elevated by inflammatory processes and can mask iron deficiency.
  • SF >100micrograms/L generally rules out IDA even in the presence of inflammatory disease.
  • If SF results are equivocal, practitioners should consider monitoring the haemoglobin (Hb) concentration in response to a trial of oral iron.

Iron studies in IDA (Refer to full guideline (on StaffNet) for GGC laboratory reference ranges) 

Serum ferritin (SF): a measure of iron storage in the body 

In the absence of inflammation, SF is the most specific test that correlates to total body iron stores. SF is the first iron study to fall and show iron deficiency. Iron deficiency is confirmed by a level below the reference interval. The normal range in an individual should take into account the variation due to age, gender and possibly ethnic origin.

A normal SF cannot exclude iron deficiency. SF shows an acute phase response such that levels may be raised by inflammation or by tissue damage. Rises may be seen in acute and chronic inflammatory disorders, infection, liver disease, renal disease and malignancy. In these patients, SF can be falsely elevated to values inappropriately high for the amount of iron in the body stores. Iron deficiency however is unlikely to be an important contributor to anaemia if SF is >100micrograms/L.

Serum iron: a measure of the amount of iron in the blood  

Highly variable and is affected by dietary iron intake, inflammation, infection and diurnal changes. Low levels cannot be interpreted in isolation because it might be seen in infection, inflammation and malignancy as well as iron deficiency.

Transferrin: carrier protein transporting iron to bone marrow 

Increases in iron deficiency to maximise utilisation of available iron.

Transferrin saturation (TSAT): measures the degree of circulating transferrin loaded with iron 

Indicator of iron immediately available to support erythropoiesis. TSAT rises in iron overload and falls in iron deficiency, but does not quantitatively reflect iron stores. Poorly specific as pregnancy, oral contraceptive use and chronic illness can result in low TSAT without iron deficiency. A short term rise in serum iron due to recent dietary iron intake can cause raised TSAT even when the patient is iron deficient.

Red cell indices: measure of the colour and size of red blood cells 

Iron deficiency impairs haem synthesis with resultant reduction in Hb content in the red blood cells (RBCs). Red blood cell indices might show a reduced mean cell haemoglobin (MCH), which corresponds to hypochromia, and a reduced mean cell volume (MCV), corresponding to microcytosis. However, not all patients with IDA will have hypochromic microcytic RBCs as they become abnormal only in long-standing iron deficiency. Red cell indices cannot be relied upon to diagnose IDA as hypochromic microcytic red cells are also seen in thalassaemia (globin deficiency leading to reduced Hb levels) and in some patients with the anaemia of chronic disease.

Interpretation of iron studies: case scenarios

(Refer to diagnostic and treatment algorithm in full guideline (on StaffNet) for further information and GGC laboratory reference ranges)

Scenario one

55 year old female with rheumatoid arthritis (RA) on maintenance methotrexate. Currently prescribed an NSAID for a flare of RA. Hb 90g/L (previous month 100g/L), erythrocyte sedimentation rate (ESR) 80mm/hr, ferritin 85micrograms/L.

  • Ferritin may be increased secondary to inflammatory processes and levels up to 100micrograms/L do not rule out IDA. Additional iron studies unlikely to provide diagnostic information.
  • Recheck full blood count and ferritin once acute flare resolved.
  • Some RA patients with persisting anaemia and inconclusive ferritin levels have iron deficiency as a contributory factor. Consider monitoring Hb concentration in response to a trial of oral iron.

Scenario two

81 year old male, Hb 105g/L, ferritin 50micrograms/L. Presents with fatigue and reduced exercise tolerance.

  • In elderly patients, iron deficiency is likely with ferritin values between 15-50micrograms/L and a level of 50-100 micrograms/L is equivocal for iron deficiency.
  • Consider monitoring symptoms and Hb concentration in response to a trial of oral iron.
  • If Hb rises in response to oral iron then consideration should be given to investigation of the cause of iron deficiency.

Scenario three

39 year old female, Hb 125g/L, ferritin 8micrograms/L, MCV and MCH normal. 

  • This is known as latent iron deficiency i.e. not anaemic but reduced body iron stores.
  • Seen in 20% of young women in the West of Scotland.
  • Menstrual blood loss or effects of pregnancies are the usual cause.
  • Seldom requires investigation unless gastrointestinal symptoms present.

 

Originally published 15/03/19 and updated 07/12/2020. Medicines Update blogs are correct at the time of publication.