What labs are recommended for a comprehensive anemia workup?

Comprehensive Anemia Workup Laboratory Testing

A complete anemia workup should include CBC with indices, reticulocyte count, peripheral blood smear, iron studies (serum iron, TIBC, ferritin, transferrin saturation), vitamin B12 and folate levels, and additional targeted testing based on morphologic classification. 1

Initial Laboratory Assessment

The initial laboratory evaluation for anemia should include:

• Complete Blood Count (CBC) with indices
  • Hemoglobin (Hb) and hematocrit (Ht)
  • Red blood cell (RBC) count
  • Mean corpuscular volume (MCV)
  • Mean corpuscular hemoglobin concentration (MCHC)
  • Red cell distribution width (RDW)
• Reticulocyte count
• Peripheral blood smear examination

These tests help classify anemia into microcytic, normocytic, or macrocytic categories based on MCV, which guides further testing 1, 2.

Secondary Testing Based on MCV Classification

For Microcytic Anemia (Low MCV):

• Iron studies:
  • Serum iron
  • Total iron binding capacity (TIBC)
  • Ferritin
  • Transferrin saturation (should be <15% in iron deficiency)
• Hemoglobin electrophoresis (if thalassemia suspected)

For Normocytic Anemia (Normal MCV):

• Iron studies (as above)
• Inflammatory markers (ESR, CRP)
• Renal function tests
• Liver function tests
• Thyroid function tests

For Macrocytic Anemia (High MCV):

• Vitamin B12 level
• Serum folate and RBC folate
• Homocysteine level (elevated in both B12 and folate deficiency)
• Methylmalonic acid (elevated specifically in B12 deficiency)
• Liver function tests
• Thyroid function tests
• Reticulocyte count

Additional Testing Based on Clinical Suspicion

• Hemolysis workup if suspected:
  • Lactate dehydrogenase (LDH)
  • Haptoglobin
  • Indirect bilirubin
  • Direct Coombs test
• Bone marrow aspiration and biopsy with cytogenetic analysis if myelodysplastic syndrome (MDS) is suspected, particularly when anemia is accompanied by other cytopenias 1

Key Diagnostic Parameters for Common Anemias

Iron Deficiency Anemia:

• Low MCV (microcytic)
• Low serum iron
• High TIBC
• Ferritin < 30 μg/L
• Transferrin saturation < 15% 1

Anemia of Chronic Disease:

• Normal MCV
• Low serum iron
• Low/Normal TIBC
• Ferritin > 100 μg/L
• Transferrin saturation < 20% 1

Important Considerations

1. Measuring both B12 and folate levels simultaneously is recommended as deficiencies can coexist 1.

2. Relying solely on hemoglobin and hematocrit without iron studies can miss iron depletion before it progresses to anemia 3.

3. RDW (red cell distribution width) improves classification accuracy and helps distinguish iron deficiency from thalassemia or anemia of chronic disease 2.

4. Before treating folate deficiency, it is essential to rule out B12 deficiency first, as treating folate deficiency alone may mask B12 deficiency and precipitate subacute combined degeneration of the spinal cord 1.

5. Patients with unexplained anemia require close follow-up every 6 months, as some may develop a primary bone marrow disorder or worsening cytopenias 1.

Pitfalls to Avoid

• Failing to measure both serum iron and ferritin can lead to missed diagnoses, as normal hemoglobin levels don't exclude iron depletion 3.

• Overlooking the need for B12 testing when folate deficiency is identified can lead to neurological complications 1.

• Not considering age and sex-specific reference ranges for hemoglobin (Hb <13.5 g/dL in males and <12.0 g/dL in females) 1, 4.

• Neglecting to assess reticulocyte count, which is crucial for distinguishing between ineffective erythropoiesis and increased red cell destruction/loss 1.

• Failing to conduct follow-up testing after initiating treatment (recommended within 3 months) 1.