What is the initial step in anemia workup and subsequent management?

Initial Anemia Workup and Management

The initial step in anemia workup should include a complete blood count (CBC) with red blood cell indices, reticulocyte count, serum ferritin, transferrin saturation, and C-reactive protein (CRP). 1 This core panel provides essential information to classify the anemia and guide subsequent management.

Diagnostic Algorithm for Anemia Workup

Step 1: Initial Laboratory Assessment

• Complete blood count (CBC) with indices
• Reticulocyte count
• Serum ferritin
• Transferrin saturation (TfS)
• C-reactive protein (CRP)

Step 2: Classification Based on MCV

While MCV-based classification has limitations 2, it provides a useful initial framework:

Microcytic Anemia (MCV <80 fL)

• Most common causes:
  • Iron deficiency anemia
  • Thalassemia
  • Anemia of chronic disease (can be microcytic)
  • Sideroblastic anemia

Normocytic Anemia (MCV 80-100 fL)

• Most common causes:
  • Acute blood loss
  • Hemolysis
  • Anemia of chronic disease/inflammation
  • Renal insufficiency
  • Bone marrow failure

Macrocytic Anemia (MCV >100 fL)

• Most common causes:
  • Vitamin B12 deficiency
  • Folate deficiency
  • Medication effects (e.g., thiopurines)
  • Alcoholism
  • Myelodysplastic syndrome

Step 3: Evaluate Reticulocyte Count

• Low/normal reticulocytes: Indicates decreased RBC production (deficiencies, bone marrow dysfunction)
• High reticulocytes: Indicates blood loss or hemolysis 1

Step 4: Iron Status Interpretation

• Absolute iron deficiency:

  • Serum ferritin <30 μg/L (in absence of inflammation)
  • Transferrin saturation <20% 1

• Iron deficiency with inflammation:

  • Serum ferritin 30-100 μg/L
  • Transferrin saturation <20%
  • Elevated CRP 1

• Anemia of chronic disease:

  • Serum ferritin >100 μg/L
  • Transferrin saturation <20%
  • Elevated inflammatory markers 1

Additional Testing Based on Initial Results

For Microcytic Anemia

• If iron deficiency confirmed: Consider GI workup to rule out blood loss 1
• If normal iron studies: Consider hemoglobinopathy evaluation

For Normocytic Anemia

• If low reticulocytes: Evaluate renal function, check for inflammation
• If high reticulocytes: Check for hemolysis (haptoglobin, LDH, bilirubin) 1

For Macrocytic Anemia

• Vitamin B12 and folate levels
• Thyroid function tests
• Liver function tests
• Medication review 1

Management Approach

Iron Deficiency Anemia

• Oral iron supplementation (first-line)
• IV iron if oral intolerance, malabsorption, or urgent need 1
• Identify and treat underlying cause

B12 Deficiency

• Cyanocobalamin supplementation
• For severe deficiency: IM injections required 3
• Monitor for hypokalemia during initial treatment 3

Anemia of Chronic Disease

• Treat underlying condition
• Consider iron supplementation if functional iron deficiency present 1

Common Pitfalls to Avoid

1. Relying solely on MCV for diagnosis: MCV-guided classification can lead to missed diagnoses in up to 90% of macrocytic anemia cases 2

2. Misinterpreting ferritin levels: Ferritin is an acute phase reactant and may be falsely elevated in inflammatory states 1

3. Overlooking mixed deficiencies: Multiple causes of anemia can coexist, particularly in elderly patients

4. Delaying B12 treatment: Neurologic damage from B12 deficiency can become irreversible if treatment is delayed 3

5. Missing underlying malignancy: Iron deficiency anemia in adults should prompt investigation for GI sources of blood loss 1

6. Inadequate monitoring: Follow-up testing is essential to confirm response to therapy and adjust treatment as needed

By following this systematic approach to anemia evaluation, clinicians can efficiently identify the underlying cause and implement appropriate management strategies to improve patient outcomes.