What is the workup for normocytic anemia?

Workup for Normocytic Anemia

The diagnostic workup for normocytic anemia should begin with a complete blood count with indices, reticulocyte count, serum ferritin, and transferrin saturation to determine the underlying cause and guide appropriate treatment. 1, 2

Initial Laboratory Evaluation

• Complete Blood Count (CBC) with indices - Confirms normocytic anemia (MCV 80-100 fL)
• Reticulocyte count - Critical for differentiating between production defects and blood loss/hemolysis
• Iron studies:
  • Serum ferritin (most useful marker for iron stores)
  • Transferrin saturation (<20% suggests iron deficiency)
  • Total Iron-Binding Capacity (TIBC)
• Peripheral blood smear - Provides morphological information about RBCs

Diagnostic Algorithm Based on Reticulocyte Count

High Reticulocyte Count (Blood Loss or Hemolysis)

1. Hemolysis workup:

   • Lactate dehydrogenase (LDH)
   • Haptoglobin (decreased in hemolysis)
   • Unconjugated bilirubin
   • Direct Coombs test (for immune-mediated hemolysis)
   • Examine for jaundice and hepatosplenomegaly 2

2. Blood loss evaluation:

   • Fecal occult blood test
   • Endoscopic evaluation if GI blood loss suspected
   • Imaging studies based on suspected source

Low/Normal Reticulocyte Count (Production Problem)

1. Anemia of inflammation/chronic disease:

   • Ferritin >100 μg/L (may be elevated due to inflammation)
   • Transferrin saturation <20%
   • Inflammatory markers (CRP, ESR)
   • Evaluate for underlying chronic conditions 1, 2

2. Chronic kidney disease:

   • BUN, creatinine, eGFR
   • Urinalysis

3. Bone marrow disorders:

   • Complete metabolic panel
   • Vitamin B12 and folate levels
   • TSH (thyroid function)
   • Consider bone marrow biopsy if other tests inconclusive 3

Special Considerations

• Anemia of chronic disease vs. iron deficiency: Use the pattern of iron studies to differentiate:

  Parameter	Iron Deficiency	Anemia of Chronic Disease
  Serum iron	Low	Low
  TIBC	High	Low/Normal
  Ferritin	<30 μg/L	>100 μg/L
  Transferrin saturation	<15%	<20%

• Mixed disorders: Patients may have both iron deficiency and anemia of chronic disease, particularly with inflammatory conditions. In these cases, ferritin may be 30-100 μg/L with transferrin saturation <20% 1

• Hemolytic anemia: Look for increased reticulocyte count, decreased haptoglobin, elevated LDH, and unconjugated hyperbilirubinemia 2

Common Pitfalls to Avoid

1. Overlooking mild anemia - Even mild normocytic anemia warrants investigation as it may indicate serious underlying disease

2. Misinterpreting ferritin in inflammatory states - Ferritin is an acute phase reactant and may be falsely elevated in inflammation; use transferrin saturation or soluble transferrin receptor for more accurate assessment 1

3. Premature diagnosis of iron deficiency - Anemia of chronic disease is often mistaken for iron deficiency and inappropriately treated with iron supplements 4

4. Failure to consider multiple causes - Normocytic anemia may have multiple contributing factors, especially in elderly patients 3

5. Overlooking drug-induced causes - Many medications can cause normocytic anemia through various mechanisms 4

The most recent evidence emphasizes the importance of a systematic approach to diagnosing normocytic anemia, with particular attention to the reticulocyte count as a key differentiating factor between production problems and blood loss/hemolysis 2. This approach allows for efficient diagnosis and targeted treatment of the underlying cause, which is the primary goal in managing normocytic anemia.