Introduction
Iron deficiency is commonly associated with anaemia, but reduced iron stores can occur even when haemoglobin levels remain within the normal range. This condition, known as iron deficiency without anaemia (IDWA) or non-anaemic iron deficiency, can be overlooked because a normal haemoglobin result may create a false sense of reassurance.
Iron plays an essential role beyond haemoglobin production, including oxygen transport, cellular energy metabolism and neurological function. Recognising iron deficiency before anaemia develops is therefore important for timely evaluation and management.
Why Does Iron Deficiency Occur Without Anaemia?
Iron deficiency develops when the body's iron stores become insufficient to meet its requirements. In the early stages, stored iron is depleted, but haemoglobin production may remain adequate. Anaemia generally develops later if the deficiency persists.
Common contributing factors include:
Menstrual blood loss: Heavy or prolonged menstrual bleeding can gradually deplete iron stores.
Inadequate dietary intake: Diets low in iron-rich foods, including certain restrictive or poorly balanced diets, may contribute.
Increased physiological requirements: Pregnancy, adolescence and periods of rapid growth increase iron requirements.
Gastrointestinal blood loss: Occult bleeding, gastrointestinal conditions or frequent blood donation may contribute to iron depletion.
Impaired absorption: Conditions such as coeliac disease, inflammatory bowel disease and previous gastrointestinal surgery can affect iron absorption.
Identifying the underlying cause is as important as correcting the deficiency.
Clinical Features: What Should Clinicians Look For?
Patients may be asymptomatic or present with nonspecific symptoms. Possible clinical features include:
Persistent fatigue or reduced energy
Poor concentration and difficulty with mental tasks
Reduced exercise tolerance
Headaches or dizziness
Hair shedding or hair loss
Restless legs symptoms
These symptoms are not specific to iron deficiency and should be interpreted alongside clinical history and laboratory findings.
Diagnosis: Do Not Rely on Haemoglobin Alone
A normal haemoglobin concentration does not exclude iron deficiency. Assessment should include a complete blood count (CBC) and iron studies, particularly serum ferritin and transferrin saturation (TSAT).
Key investigations include:
Haemoglobin (Hb): Helps determine whether anaemia is present.
Serum ferritin: Reflects the body's iron stores. A ferritin level below 30 µg/L generally supports iron deficiency in adults without inflammation.
Transferrin saturation (TSAT): A TSAT below 20% may support iron deficiency, particularly when interpreted alongside ferritin.
Inflammatory markers: C-reactive protein (CRP) may help interpret ferritin when inflammation is suspected.
Ferritin is an acute-phase reactant and may appear normal or elevated in inflammatory conditions despite depleted or unavailable iron. In these situations, ferritin should not be interpreted in isolation; TSAT and the clinical context become particularly important.
Management: Address the Cause and Replenish Iron Stores
Management should be individualised according to the severity of deficiency, symptoms, underlying cause and patient-specific factors.
1. Identify and manage the underlying cause
Assess for menstrual or gastrointestinal blood loss, inadequate dietary intake, malabsorption and increased physiological requirements. Persistent or unexplained iron deficiency warrants further investigation.
2. Consider iron replacement
Oral iron is commonly used as the initial treatment when replacement is indicated and the patient can tolerate it. Gastrointestinal adverse effects, including nausea, constipation and abdominal discomfort, may affect adherence.
Intravenous iron may be considered in selected patients, such as those with malabsorption, intolerance or inadequate response to oral treatment, or specific clinical circumstances requiring more rapid replacement.
3. Monitor treatment response
Repeat iron studies are important to assess whether iron stores are recovering. The timing of reassessment should be individualised according to the treatment plan and clinical context. Persistent deficiency should prompt reassessment of adherence, ongoing blood loss, absorption and the original diagnosis.