What is the diagnostic approach for iron deficiency anemia?

Diagnostic Approach for Iron Deficiency Anemia

The diagnosis of iron deficiency anemia requires a minimum workup including complete blood count with red cell indices (RDW and MCV), reticulocyte count, serum ferritin, transferrin saturation, and C-reactive protein. 1, 2

Diagnostic Parameters

Initial Assessment

• Hemoglobin levels below WHO thresholds indicate anemia:
  • Men: <13.0 g/dL
  • Non-pregnant women: <12.0 g/dL
  • Pregnant women: <11.0 g/dL
  • Children (varies by age): 11.0-12.0 g/dL 1

Key Diagnostic Tests

1. Complete Blood Count (CBC):

   • Hemoglobin and hematocrit (late indicators of iron deficiency)
   • Red cell indices: MCV (mean corpuscular volume) and RDW (red cell distribution width)
   • Typically shows microcytic (low MCV) and hypochromic pattern 1, 2

2. Iron Status Parameters:

   • Serum ferritin: Most sensitive test for iron stores
     • <30 μg/L indicates iron deficiency without inflammation
     • 30-100 μg/L with elevated CRP may still indicate iron deficiency with concurrent inflammation 1, 2
   • Transferrin saturation: <20% suggests iron deficiency 2
   • C-reactive protein (CRP): Essential to interpret ferritin in context of inflammation 1, 2

3. Additional Tests (when diagnosis remains unclear):

   • Reticulocyte count: Low or normal indicates inappropriate response to anemia
   • Serum vitamin B12 and folate: To rule out other causes of anemia
   • Percentage of hypochromic red cells
   • Reticulocyte hemoglobin content
   • Soluble transferrin receptor 1

Diagnostic Algorithm

1. Step 1: Confirm anemia based on hemoglobin levels using WHO criteria
2. Step 2: Assess MCV and RDW
   • Microcytic (low MCV) with high RDW suggests iron deficiency
   • Note: Normal MCV doesn't exclude iron deficiency, especially when macrocytosis and microcytosis coexist 1
3. Step 3: Evaluate iron parameters
   • Check serum ferritin, transferrin saturation, and CRP
   • Interpret ferritin based on inflammatory status:

     Inflammatory Status	Ferritin Threshold
     No inflammation	<30 μg/L
     With inflammation	<100 μg/L

4. Step 4: Consider reticulocyte count
   • Low/normal reticulocytes suggest deficiency or bone marrow disease
   • Increased reticulocytes suggest hemolysis 1

Diagnostic Challenges and Pitfalls

• Coexisting conditions: Iron deficiency may coexist with anemia of chronic disease, making diagnosis more complex 1, 2
• Inflammation effect: Inflammation elevates ferritin (acute phase reactant), potentially masking iron deficiency 1, 2
• Relying solely on hemoglobin/hematocrit: These are late indicators and may miss early iron deficiency 1, 3
• Normal MCV: Iron deficiency can present with normal MCV when microcytosis and macrocytosis coexist 1
• Multiple etiologies: Several causes of iron deficiency often coexist in a single patient 4

Special Considerations

• In patients with chronic inflammatory conditions (IBD, chronic kidney disease, heart failure), use higher ferritin thresholds (up to 100 μg/L) to diagnose iron deficiency 1, 2
• Consider consulting a hematologist when the cause of anemia remains unclear despite extensive workup 1
• After diagnosing iron deficiency anemia, investigate underlying causes (blood loss, malabsorption, increased requirements) 5
• Avoid assuming low iron intake as the cause without proper investigation 1

By following this systematic approach, iron deficiency anemia can be accurately diagnosed, allowing for appropriate treatment and investigation of underlying causes.