Iron deficiency

Iron deficiency is common in Australia, affecting up to 20% of people during their lifetime. Iron deficiency can stem from multiple causes, including low intake of iron-rich foods, reduced absorption or excessive loss of iron, which is usually due to blood loss1-3.

It is important to be able to accurately diagnose iron deficiency. Incorrect interpretation of iron studies can lead to unnecessary, and potentially harmful, investigations.

If iron deficiency is present, screening questions can be used to determine if dietary intake is insufficient, or menorrhagia is the likely cause. If this is not the case, the patient will require further investigation for the next most common cause – gastrointestinal blood loss.

Who is at risk?

  • Menstruating women (9-11% are iron deficient)
  • Pregnant women (up to 25% may be iron deficient)
  • Elderly, aged >65 years

Symptoms

  • Fatigue
  • Lethargy, irritability
  • Headache
  • Exercise intolerance, exertional dyspnoea, angina
  • Symptoms related to cause (eg menorrhagia, haemoptysis, melena, rectal bleeding, change in bowel habit)

Diagnosing iron deficiency

Iron deficiency progresses in stages. In the first stage, iron stores can be depleted without causing anemia. Symptoms may occur at this stage (with low iron stores, but no anemia), in particular fatigue and reduced exercise tolerance.

Further iron loss will initially cause normocytic anemia. Many patients in Australia present at this stage. Ongoing loss will result in microcytic hypochromic anemia.

Iron studies and full blood examination are preformed to diagnose iron deficiency. Iron studies need to be interpreted in the context of the clinical scenario, as an inflammatory process can impact on interpretation of the results.

Interpretation of iron studies in iron deficiency

Test Interpretation Iron Deficient state Inflammatory response
Ferritin (single best test) Accurately reflects iron stores

Commonly elevated in inflammatory states including chronic disease

>100 μg/L excludes deficiency

Low

(<30 μg/L *)

 

 

High

 

Serum Iron Not clinically useful due to significant variation within the same day. Levels may be suppressed in inflammation Low Low
Serum transferrin (or TIBC – total iron binding capacity) Iron binds to transferrin. TIBC is a measure of transferrin. High Low
Transferrin saturation (serum iron/TIBC) Transferrin levels are reduced with inflammation Low Low
Soluble transferrin receptor Directly linked to rate of erythropoiesis and inversely to iron stores. Not affected by inflammation. Not available with routine iron studies (specific request) – useful if concurrent inflammation and  suspicion of low iron stores High Normal

* A lower cutoff of <15 μg/L may miss some patients (75% sensitive). Value of <30 μg/L are over 90% sensitive in diagnosing iron deficiency.

In some cases it can be difficult to clearly establish if anemia is due to inflammation alone, or there is co-existent iron deficiency. If the inflammatory cause is transient, iron studies may be repeated once the inflammation has subsided. In the setting of chronic inflammation, if iron studies are equivocal, one option is to give iron replacement and observe for a response – a rise in haemoglobin in response to iron replacement is supportive of iron deficiency.

Common causes of iron deficiency in Australia3-4

  • Diet
  • Women
  • Heavy menstrual loss
  • Pregnancy/lactation
  • Malabsorption (celiac, H pylori gastritis, Inflammatory bowel disease)
  • Gastrointestinal losses (peptic ulcer disease, IBD, bowel cancer/large adenomas, NSAID induced ulcers)
  • Chronic disease including heart failure, chronic kidney disease (and haemodialysis)

This is not an exhaustive list of all differentials, rather a summary of the more likely causes.

Treating iron deficiency

Oral supplementation (100-200 mg daily)

  • Side effects can include metallic taste, constipation and nausea
  • Cheap, easy to administer
  • Should be given in divided doses when using >1 tablet/day to avoid saturation of uptake

Parenteral

  • Ferinject intravenous preparation (500mg to 1g) allows shortest infusion time (~15 minutes)
  • Circumvents problems of absorption and poor compliance

Approach to iron deficiency in pre-menopausal women

Initial screening for gastrointestinal (GI) symptoms and menorrhagia (or recent pregnancy/ongoing lactation) should be done. If there are no GI symptoms, and menstrual loss is high, it is reasonable to supplement iron intake and monitor ferritin. Further investigation is warranted if iron levels fail to increment.

Likelihood of gastrointestinal blood loss

Some studies document up to 15% of patients presenting with asymptomatic iron deficiency were found to have a high risk lesion such as malignancy or advanced adenoma. However, this was <4% in those aged less than 45 years5.

If gastrointestinal symptoms are present, or no apparent cause for low iron is present on history, further investigation with gastroscopy and colonoscopy is recommended. FOBT is not useful in this scenario – it is not sensitive nor specific enough to definitively exclude GI causes for low iron.

References:
1. Guyatt GH, Oxman AD, Ali M et al. J Gen Int Med 1992; 7(2): 1945.
2. Camaschella C. Iron deficiency anemia. N Eng J Med. 2015; 372 (19): 1832-43.
3. Weiss G and Goodnough L. Anemia of Chronic Disease. N Eng J Med 2005; 352: 1011-1023.
4. Khadem G, Scott IA, Klein K. Evaluation of iron deficiency anemia in tertiary hospital settings: room for improvement? Int J Med. 2012; 42 (6): 658-64.
5. Ho CH, Chau WK, Hsu HC et al. Predictive risk factors and prevalence of malignancy in patients with iron deficiency in Taiwan. Am J Haematol. 2005; 78 (2): 108.


Ola Niewiadomski updatedAUTHOR | Dr Ola Niewiadomski
Dr Niewiadomski is a gastroenterologist who has a broad range of interests in all areas of gastroenterology including inflammatory bowel disease, irritable bowel syndrome, ensoscopic procedures and hepatology.
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PH | 03 9417 7768  FAX | 03 9415 1069                                               EMAIL | dr.ola@prontonmail.com

 

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