What is the initial hematologic workup for iron deficiency anemia?

Initial Hematologic Workup for Iron Deficiency Anemia

The initial hematologic workup for iron deficiency anemia should include a complete blood count with red cell indices, serum ferritin, transferrin saturation, and screening for celiac disease. 1, 2

Core Laboratory Tests

First-Line Tests

• Complete Blood Count (CBC) with differential
  • Hemoglobin and hematocrit levels
  • Red cell indices (MCV, MCH, MCHC)
  • Red cell distribution width (RDW)
  • Peripheral blood smear examination

Iron Studies

• Serum ferritin (most specific test for iron deficiency)

  • <15 μg/L: highly specific for iron deficiency (specificity 0.99) 1
  • <30 μg/L: indicates absent/low iron stores in non-inflammatory states 1, 2
  • <45 μg/L: optimal cutoff for clinical practice (specificity 0.92) 1
  • 30-100 μg/L with inflammation: may still indicate iron deficiency 1, 2

  • 150 μg/L: unlikely to be iron deficiency even with inflammation 1

• Transferrin saturation (<20% suggests iron deficiency) 1, 2

• Serum iron and total iron-binding capacity (TIBC) 1

Additional Tests

• Celiac disease screening (3-5% of IDA cases are due to celiac disease) 1
  • Serological testing first
  • Small bowel biopsy only if serology is positive

Interpretation of Results

Diagnostic Criteria

• Iron deficiency without inflammation: Ferritin <30 μg/L 1, 2
• Iron deficiency with inflammation: Ferritin 30-100 μg/L with transferrin saturation <20% 1, 2
• Anemia of chronic disease: Ferritin >100 μg/L and transferrin saturation <20% 1
• Combined iron deficiency and anemia of chronic disease: Ferritin 30-100 μg/L 1, 2

Therapeutic Trial

• A good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) strongly suggests iron deficiency, even with equivocal iron studies 1

Special Considerations

Inflammatory Conditions

• In patients with inflammatory conditions (e.g., IBD, chronic infections), ferritin acts as an acute phase reactant and may be falsely elevated despite iron deficiency 1, 2
• In these cases:
  • Use higher ferritin cutoffs (up to 100 μg/L)
  • Consider additional markers like transferrin saturation
  • Check C-reactive protein (CRP) to assess inflammation 2

Chronic Kidney Disease

• For patients with eGFR <60 mL/min/1.73m², consider:
  • Erythropoietin level measurement
  • Different diagnostic thresholds for iron studies 1, 2

Common Pitfalls to Avoid

1. Relying solely on hemoglobin/hematocrit: These decrease only in severe iron deficiency and can miss early depletion 3

2. Misinterpreting ferritin in inflammatory states: Ferritin can be falsely elevated in inflammation despite iron deficiency 2

3. Overlooking non-anemic iron deficiency: Iron stores can be depleted (hypoferritinemia) before anemia develops 1

4. Failing to investigate mild anemia: Even mild anemia, especially in men and postmenopausal women, warrants thorough investigation 2

5. Not considering hemoglobinopathies: In patients with microcytosis and normal iron studies, consider hemoglobin electrophoresis, particularly in appropriate ethnic backgrounds 1

Next Steps After Initial Workup

• If iron deficiency anemia is confirmed, proceed with:
  • Gastrointestinal evaluation (bidirectional endoscopy) for men and postmenopausal women 1
  • Initiation of iron replacement therapy while awaiting further investigations 1
  • Follow-up CBC in 4-8 weeks to assess response to treatment 2

By following this structured approach to the hematologic workup of iron deficiency anemia, clinicians can accurately diagnose the condition and identify its underlying cause, leading to appropriate treatment and improved patient outcomes.