What diagnostic tests are indicated when Iron Deficiency Anemia (IDA) is a consideration?

Diagnostic Testing for Iron Deficiency Anemia

When IDA is suspected, confirm iron deficiency with serum ferritin (the single most useful marker) before proceeding with investigations to identify the underlying cause, which should include urinalysis, coeliac disease screening, and bidirectional endoscopy in at-risk populations. 1

Initial Laboratory Confirmation

Essential Iron Studies

• Serum ferritin is the most powerful and specific test for iron deficiency 1

  • Ferritin <15 μg/L is diagnostic of absent iron stores 1
  • Ferritin <30 μg/L generally indicates low body iron stores 1, 2
  • Critical caveat: Ferritin is an acute phase protein and can be falsely elevated in inflammation, malignancy, or hepatic disease 1
  • In inflammatory states, ferritin <100 μg/L may still indicate iron deficiency 3

• Transferrin saturation <20-30% supports the diagnosis when ferritin is equivocal 1, 2

• Hemoglobin concentration below the lower limit of normal for your laboratory's reference range defines anemia 1

  • WHO defines anemia as Hb <130 g/L in men, <120 g/L in non-pregnant women, <110 g/L in pregnant women (2nd/3rd trimester) 1

Complete Blood Count Parameters

• Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) typically show microcytosis and hypochromia 1

  • Important pitfall: Normal MCV does not exclude iron deficiency, especially in early stages or combined deficiencies 3, 4
  • MCH may be more sensitive than MCV for detecting iron deficiency 1

• Red cell distribution width (RDW) may be elevated, particularly in combined deficiencies 1

Therapeutic Trial as Diagnostic Tool

• A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy is highly suggestive of absolute iron deficiency, even when iron studies are equivocal 1

Investigations to Identify Underlying Cause

Mandatory Initial Workup

All patients with confirmed IDA require the following investigations 1:

• Urinalysis or urine microscopy to exclude renal tract blood loss 1

• Coeliac disease screening (serological testing for tissue transglutaminase antibodies)

  • Found in 3-5% of IDA cases 1
  • Can also be diagnosed on small bowel biopsy during gastroscopy 1

• Detailed history focusing on:

  • Dietary iron intake 1
  • Menstrual blood loss patterns 2
  • NSAID/aspirin use 1, 2
  • Gastrointestinal symptoms 1
  • Previous gastric surgery 1, 5

Gastrointestinal Endoscopy

In men and postmenopausal women with newly diagnosed IDA, gastroscopy and colonoscopy should be first-line GI investigations 1:

• Bidirectional endoscopy is standard because GI malignancies (colorectal and gastric cancer) commonly present with IDA 1
• CT colonography is a reasonable alternative if colonoscopy is not suitable 1
• Premenopausal women <40 years may not require bidirectional endoscopy unless red flags are present 5

Further Investigation When Initial Workup is Negative

If bidirectional endoscopy is negative and IDA persists or recurs despite iron therapy 1:

• Capsule endoscopy is the preferred test for small bowel examination (highly sensitive for mucosal lesions) 1
• CT/MR enterography are complementary for inflammatory and neoplastic small bowel disease 1
• Further renal tract investigation if not already completed 1

Tests NOT Currently Recommended

• Faecal immunochemical testing (FIT) for risk stratification in IDA patients has insufficient evidence at present, though this may change 1

Key Clinical Pitfalls to Avoid

• Do not rely on hemoglobin and hematocrit alone—they decrease only with severe iron depletion and can miss early iron deficiency 4
• Do not assume normal ferritin excludes iron deficiency in patients with inflammation, chronic disease, malignancy, or liver disease 1, 3
• Do not delay iron replacement therapy while awaiting investigations unless colonoscopy is imminent 1
• Do not assume dietary insufficiency or menstrual loss is the cause without completing appropriate investigations, as GI pathology including cancer must be excluded 1