Laboratory Workup for Iron Deficiency Anemia
Order hemoglobin/hematocrit and serum ferritin as your initial diagnostic tests—these two tests alone can confirm iron deficiency anemia in most cases. 1
Initial Essential Tests
Complete blood count (CBC) with hemoglobin/hematocrit: Anemia is defined as hemoglobin <13 g/dL in men, <12 g/dL in non-pregnant women, and <11 g/dL in pregnant women 2, 1
Serum ferritin: This is the single most specific test for iron deficiency 2, 1
Red cell indices from the CBC (automatically included): Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW) provide supporting evidence, with microcytosis and hypochromia being characteristic findings 2, 1
Additional Tests When Ferritin is Equivocal (15-99 µg/L)
When ferritin falls in the intermediate range or you suspect false-normal ferritin due to inflammation, order:
Transferrin saturation (TSAT): Calculated as serum iron/total iron-binding capacity × 100 2, 3
Total iron-binding capacity (TIBC): Elevated TIBC (>70 µmol/L) supports iron deficiency 4
Serum iron: Low serum iron combined with elevated TIBC strengthens the diagnosis 2, 4
Tests for Special Circumstances
C-reactive protein (CRP): Order this when you suspect inflammation is falsely elevating ferritin, since ferritin is an acute-phase reactant 2, 1
Serum transferrin receptor (sTfR): Useful to distinguish iron deficiency from anemia of chronic disease in patients with inflammatory conditions 1
Hemoglobin electrophoresis: Order in patients with microcytosis but normal iron studies, particularly in those of appropriate ethnic background, to rule out thalassemia trait 2
Tissue transglutaminase (TTG) antibodies: Test for celiac disease in patients with unexplained iron deficiency (assuming they haven't been gluten-free for at least 6 weeks) 2
Diagnostic Confirmation Strategy
- Therapeutic trial of oral iron: A hemoglobin rise ≥10 g/L within 2 weeks is highly suggestive of absolute iron deficiency, even if iron studies are equivocal 2, 1
Common Pitfalls to Avoid
Don't rely on ferritin alone in inflammatory states: Ferritin can be falsely normal or elevated in patients with infection, inflammation, liver disease, or malignancy 2
Don't miss functional iron deficiency: Some patients have ferritin >30 µg/L but still have inadequate iron for erythropoiesis—check TSAT in these cases 2
Don't order excessive tests initially: The combination of hemoglobin and ferritin is sufficient for diagnosis in most straightforward cases 1
Don't forget IgA deficiency: If TTG is negative but celiac disease is still suspected, check IgA levels since IgA deficiency can cause false-negative TTG results 2