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Iron deficiency without anaemia

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Non-anaemic iron deficiency

Iron deficiency without anaemia is common (1).

Patients may present with unexplained, non-specific symptoms.

Ferritin is an indicator of iron stores and is the most sensitive and specific biomarker for assessing iron defiency

  • WHO defines low ferritin as levels <15 µg/L for adults and <12 µg/L for children (2)
    • note though that, in clinical practice, when ferritin levels dip below 30 µg/L, iron deficiency can be ascertained
    • ferritin is an acute-phase reactant that is increased in serum during chronic inflammation

Transferrin saturation (TSAT) levels below 20% are also diagnostic of iron deficiency (2)

  • in chronic inflammatory conditions when ferritin levels are 100-300 µg/L, TSAT should be used to diagnose iron deficiency

Iron deficiency anemia (hemoglobin <=130 g/L in males and <=120 g/L in females) is a late manifestation of iron deficiency, both of which are common medical conditions in everyday clinical practice (3)

  • 10-20% of menstruating women have iron deficiency, and 3-5% of them are frankly anemic

Iron studies will usually show a low ferritin and low transferrin saturation with a normal haemoglobin concentration.

The cause of the iron deficiency should be identified and managed.

  • iron deficiency can occur secondary to:
    • inadequate dietary intake, increased requirements (e.g. pregnancy and breastfeeding),
    • impaired absorption (e.g. coeliac disease, bariatric surgery), or
    • blood loss (e.g. menstrual, blood donation, gastrointestinal)
    • drug-induced causes of iron deficiency should be considered:
      • particularly regarding anticoagulants, over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet drugs

  • iron studies assist in the differential diagnosis of iron deficiency
    • a reduced ferritin is the most reliable initial marker to diagnose iron deficiency without anaemia
      • note that although WHO defines low serum ferritin as less than 12 microgram/L in adults, a concentration of less than 30 microgram/L has a high sensitivity (92%) and specificity (98%) for iron deficiency,correlating with the absence of iron stores in the bone marrow (1)
      • changes in iron status before the development of anaemia may be suggested on a full blood count by falling values for mean cell haemoglobin and mean corpuscular volume and an increased red cell distribution width

There is limited evidence about the benefits of giving iron to people who do not have anaemia. If there is iron deficiency, most people can be given oral iron supplements (1,2,3)

  • should be treated when identified, with a target ferritin of 100 µg/L (2)
    • treatment should be continued until ferritin levels have normalised and symptoms have resolved
    • patients should be offered dietary advice and oral iron replacement
    • consider IV replacement should be considered for symptomatic patients with treatment-resistant iron deficiency without anaemia
    • monitor ferritin levels every 6-12 months following treatment, especially in heavily menstruating women and those considering pregnancy

Reference:

  • (1) Balendran S, Forsyth C. Non-anaemic iron deficiency. Aust Prescr. 2021 Dec;44(6):193-196.
  • (2) Al-Naseem A, Sallam A, Choudhury S, Thachil J. Iron deficiency without anaemia: a diagnosis that matters. Clin Med (Lond). 2021 Mar;21(2):107-113.
  • (3) Soppi ET. Iron deficiency without anemia - a clinical challenge Clinical Case Reports 2018; 6(6): 1082-1086.

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