What lab values indicate iron deficiency?

Laboratory Values Indicating Iron Deficiency

Serum ferritin concentration is the most specific indicator available of depleted iron stores, with levels ≤15 μg/L confirming iron deficiency in adults. 1

Primary Diagnostic Tests

Serum Ferritin

• Without inflammation:

  • <30 μg/L indicates iron deficiency 1
  • <15 μg/L indicates absolute iron deficiency with high specificity (98%) 1
  • <12 μg/L has even higher specificity (100%) but lower sensitivity (61%) 1
  • Recent research suggests ≤50 ng/mL may indicate early iron deficiency 2

• With inflammation/chronic disease:

  • <100 μg/L suggests iron deficiency 1
  • 30-100 μg/L with inflammation likely indicates combined iron deficiency and anemia of chronic disease 1

Transferrin Saturation

• <16% indicates iron deficiency 1
• Calculated as: (serum iron concentration/TIBC) × 100 1
• Less sensitive than ferritin but useful when combined with other tests 1

Additional Diagnostic Parameters

Erythrocyte Protoporphyrin

• 30 μg/dL of whole blood or >70 μg/dL of red blood cells in adults 1

• 80 μg/dL of red blood cells in children aged 1-2 years 1

• Earlier indicator of iron-deficient erythropoiesis than anemia 1

Complete Blood Count Parameters

• Mean Corpuscular Volume (MCV): Low values indicate microcytic anemia 1
• Red Blood Cell Distribution Width (RDW): >14.0% with low MCV suggests iron-deficiency anemia 1
• Hemoglobin/Hematocrit: Late indicators of iron deficiency 1
  • Values below 5th percentile for age/sex/pregnancy status 1

Total Iron-Binding Capacity (TIBC)

• Typically elevated in iron deficiency 1
• Less sensitive than ferritin for detecting iron deficiency 1

Diagnostic Algorithm

1. First-line testing: Serum ferritin + transferrin saturation

   • If ferritin ≤15 μg/L: Confirms iron deficiency
   • If ferritin >15 μg/L but <100 μg/L with inflammation: Consider iron deficiency

2. If results are equivocal (ferritin 30-100 μg/L):

   • Check inflammatory markers (CRP, ESR)
   • Consider soluble transferrin receptor (sTfR) measurement (high in iron deficiency, normal/low in anemia of chronic disease) 1

3. Additional testing for anemia characterization:

   • Complete blood count with MCV and RDW
   • Erythrocyte protoporphyrin concentration

Important Caveats

• Ferritin limitations: As an acute-phase reactant, ferritin can be falsely elevated in inflammatory conditions, infections, liver disease, and malignancies 1

• Transferrin saturation limitations:

  • Diurnal variation (higher in morning, lower at night) 1
  • Day-to-day variation within individuals 1
  • Affected by recent meals (serum iron increases after eating) 1

• Diagnostic challenges in specific populations:

  • Pregnant women (especially 2nd/3rd trimester) 3
  • Patients with chronic inflammatory conditions (IBD, CKD, heart failure) 3
  • Post-bariatric surgery patients 3

• When to suspect combined iron deficiency and anemia of chronic disease:

  • Ferritin 30-100 μg/L
  • Transferrin saturation <16%
  • Evidence of inflammation 1

Remember that early iron deficiency may be present without anemia, and proper diagnosis is essential for preventing progression to iron-deficiency anemia and associated morbidity.