What labs should I order for a patient with suspected Iron Deficiency Anemia (IDA)?

Laboratory Workup for Suspected Iron Deficiency Anemia

Order a complete blood count (CBC) with hemoglobin, serum ferritin, and celiac disease serology (tissue transglutaminase antibody with IgA level) as your initial laboratory evaluation for suspected IDA. 1

Essential Initial Labs

Confirm Anemia

• Hemoglobin threshold: <13 g/dL in men or <12 g/dL in non-pregnant women 1
• The CBC will also provide mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), which typically show microcytosis and hypochromia in IDA, though MCH may be more reliable than MCV 1

Confirm Iron Deficiency

• Serum ferritin is the single most powerful test for iron deficiency 1
• Use ferritin <45 ng/mL as your diagnostic cutoff (not the traditional <15 ng/mL), as this provides optimal sensitivity and specificity 1
• This higher threshold is particularly important because ferritin is an acute phase reactant and can be falsely elevated in inflammation, chronic kidney disease, or other inflammatory states 1

Screen for Celiac Disease

• Order tissue transglutaminase (TTG) antibody with total IgA level in all patients with suspected IDA 1
• Celiac disease is found in 3-5% of IDA cases and is a well-recognized cause even in asymptomatic patients 1
• The IgA level is critical because IgA deficiency is relatively common and will cause falsely negative TTG results 1

Additional Labs When Ferritin is Equivocal

If ferritin is between 45-100 ng/mL and you suspect iron deficiency in the context of inflammation or chronic disease:

• Transferrin saturation <30% supports iron deficiency 1
• Serum iron and total iron-binding capacity (TIBC) can help clarify the diagnosis 1
• Consider measuring serum transferrin receptor if available, as it is less affected by inflammation 1

Other Essential Initial Tests

• Urinalysis or urine microscopy to exclude renal causes of blood loss 1
• Reticulocyte count as part of the anemia workup 1

Important Caveats

When Iron Studies Are Equivocal

• A therapeutic trial of iron with hemoglobin rise ≥10 g/L within 2 weeks is highly suggestive of absolute iron deficiency, even if iron studies are borderline 1
• This response essentially confirms the diagnosis retrospectively 1

Don't Forget These Scenarios

• In patients with microcytosis but normal iron studies, particularly those of appropriate ethnic background, order hemoglobin electrophoresis to exclude thalassemia 1
• Ferritin can be falsely normal in iron deficiency when there is concurrent inflammation, chronic kidney disease, liver disease, or malignancy 1

What NOT to Order Routinely

• Avoid routine gastric biopsies for atrophic gastritis during endoscopy 1
• Bone marrow biopsy is rarely necessary and only considered when diagnosis remains unclear after all other testing 1, 2

Clinical Context Matters

The laboratory confirmation of IDA should prompt urgent gastrointestinal investigation in most adults, as IDA can be the presenting sign of GI malignancy 1. The specific approach to further workup (endoscopy, etc.) depends on patient demographics, with men and postmenopausal women requiring more aggressive investigation than premenopausal women 1.