What is the initial step in testing for iron deficiency?

Initial Testing for Iron Deficiency

Serum ferritin is the single most powerful initial test for diagnosing iron deficiency, with a cutoff of <45 ng/mL recommended for patients with anemia, though <12-15 ng/mL is diagnostic in the absence of inflammation. 1

Primary Diagnostic Approach

First-Line Test: Serum Ferritin

• Serum ferritin <45 ng/mL is the recommended threshold for diagnosing iron deficiency in patients with anemia, based on strong evidence from the American Gastroenterological Association (AGA) 1
• Ferritin <12 μg/dL is definitively diagnostic of iron deficiency in patients without inflammatory conditions 1
• Ferritin is superior to other tests because it directly reflects total body iron stores 1

Important Caveats with Ferritin

• Ferritin >100 μg/dL essentially rules out iron deficiency, even in inflammatory states 1
• Ferritin can be falsely elevated in patients with concurrent chronic inflammation, malignancy, hepatic disease, or chronic kidney disease 1
• In these inflammatory conditions, additional laboratory tests beyond ferritin may be needed to confirm the diagnosis 1

Supplementary Iron Studies (When Ferritin is Equivocal)

When ferritin levels are borderline (12-100 μg/dL) or when inflammation is suspected:

• Transferrin saturation <20-30% supports iron deficiency diagnosis 1, 2
• Calculate as: (serum iron/total iron binding capacity) × 100 1, 2
• Other supportive tests include elevated total iron-binding capacity and serum transferrin receptor levels 1

Complete Blood Count Findings

While not diagnostic alone, CBC parameters provide supportive evidence:

• Microcytic, hypochromic anemia (low MCV) is characteristic but occurs late in iron deficiency 1
• Elevated red cell distribution width (RDW) may indicate combined deficiency (e.g., with folate) 1
• Hemoglobin and hematocrit are late indicators, occurring only after iron stores are depleted 1

Common Pitfall to Avoid

Do not assume microcytosis equals iron deficiency—thalassemia, hemoglobinopathies, and anemia of chronic disease can also cause microcytosis 1. Hemoglobin electrophoresis should be performed in patients of appropriate ethnic background with microcytosis before extensive GI investigation 1.

Functional Confirmation

• A hemoglobin rise ≥10 g/L within 2 weeks of oral iron therapy is highly suggestive of absolute iron deficiency, even if initial iron studies were equivocal 1
• This therapeutic trial can serve as a diagnostic test when laboratory results are unclear 1

Algorithm Summary

1. Start with serum ferritin as the initial test 1
2. If ferritin <45 ng/mL (or <12-15 ng/mL without inflammation): iron deficiency confirmed 1
3. If ferritin 12-100 ng/mL with suspected inflammation: add transferrin saturation 1
4. If ferritin >100 ng/mL: iron deficiency essentially excluded 1
5. If diagnosis remains uncertain: consider therapeutic trial of oral iron with hemoglobin recheck in 2 weeks 1