What is the initial workup for a patient presenting with normocytic anemia?

Initial Workup for Normocytic Anemia

The initial workup for normocytic anemia should include complete blood count with reticulocyte count, peripheral blood smear examination, iron studies (ferritin, transferrin saturation), and assessment of renal function to determine the underlying cause and guide appropriate treatment. 1

Step-by-Step Diagnostic Approach

1. Confirm Anemia and Classification

• Verify hemoglobin levels (<13.5 g/dL in adult males and <12.0 g/dL in adult females) 1
• Confirm normocytic status (MCV 80-100 fL)
• Review RBC distribution width (RDW) to help differentiate causes

2. First-line Laboratory Tests

• Complete blood count (CBC) with indices
• Reticulocyte count - critical for determining if anemia is due to decreased production or increased destruction/loss 1
  • Low reticulocyte count: suggests bone marrow production problem
  • High reticulocyte count: suggests hemolysis or blood loss
• Peripheral blood smear - to evaluate RBC morphology 2
• Iron studies:
  • Serum ferritin
  • Transferrin saturation (TSAT)
  • Total iron-binding capacity (TIBC)
• Renal function tests - BUN, creatinine (especially if creatinine ≥2 mg/dL) 3

3. Additional Testing Based on Clinical Suspicion

• Inflammatory markers: ESR, CRP (for anemia of chronic disease)
• Hemolysis evaluation if suspected:
  • Lactate dehydrogenase (LDH)
  • Haptoglobin
  • Unconjugated bilirubin
  • Direct Coombs test 2
• Nutritional assessment:
  • Vitamin B12 and folate levels 1
• Thyroid function tests (hypothyroidism can cause normocytic anemia) 3
• Stool guaiac test for occult blood (if iron deficiency is detected) 3

Diagnostic Algorithm Based on Reticulocyte Count

Low Reticulocyte Count

• Anemia of chronic disease/inflammation

  • Normal/elevated ferritin
  • Low TSAT
  • Normal/slightly elevated RDW 1

• Anemia of chronic kidney disease

  • Evaluate if creatinine ≥2 mg/dL
  • EPO deficiency likely (EPO level measurement usually not indicated) 3

• Bone marrow disorders

  • Consider if abnormalities in multiple cell lines
  • Bone marrow examination indicated if:
    • Abnormalities in multiple cell lines
    • Presence of immature granulocytes
    • Unexplained persistent anemia 1

High Reticulocyte Count

• Acute blood loss

  • Recent history of bleeding
  • Hemodynamic changes

• Hemolytic anemia

  • Elevated LDH, decreased haptoglobin
  • Increased unconjugated bilirubin
  • Positive Coombs test (if autoimmune) 4

Common Pitfalls to Avoid

1. Inadequate investigation: Failing to evaluate for underlying causes beyond the obvious 1

2. Misdiagnosis: Confusing anemia of chronic disease with iron deficiency anemia, leading to inappropriate iron supplementation 5

3. Premature bone marrow examination: Bone marrow studies should be reserved for cases where non-invasive testing fails to identify the cause or when multiple cell lines are affected 6

4. Overlooking kidney disease: Anemia can develop with serum creatinine as low as 2.0 mg/dL due to EPO deficiency 3

5. Missing concurrent nutritional deficiencies: Even in normocytic anemia, deficiencies of iron, B12, or folate may be present 1

By following this systematic approach to normocytic anemia workup, clinicians can efficiently identify the underlying cause and initiate appropriate treatment to improve patient outcomes and quality of life.