What laboratory tests are used to diagnose anemia?

Laboratory Tests for Diagnosing Anemia

A comprehensive anemia workup should include a complete blood count with red cell indices, reticulocyte count, serum ferritin, transferrin saturation, and additional tests for vitamin deficiencies to accurately diagnose the type and cause of anemia. 1

Initial Laboratory Assessment

• Complete blood count (CBC) is essential and should include:

  • Hemoglobin concentration
  • Hematocrit
  • Red blood cell count
  • Red cell indices (MCV, MCH, MCHC)
  • White blood cell count with differential
  • Platelet count 2, 1

• Reticulocyte count is crucial to assess bone marrow response to anemia and distinguish between decreased production versus increased destruction/loss of red blood cells 2, 1

• Iron studies are necessary for proper evaluation:

  • Serum ferritin (most sensitive test for iron stores)
  • Transferrin saturation (TSAT)
  • Serum iron level 2, 1

Classification-Based Testing

• For microcytic anemia (MCV < 80 fL):

  • Iron studies are essential (ferritin, TSAT)
  • Consider hemoglobin electrophoresis if thalassemia is suspected 1

• For normocytic anemia (MCV 80-100 fL):

  • Reticulocyte count to determine if there is appropriate bone marrow response
  • C-reactive protein to assess for inflammation
  • Kidney function tests to evaluate for renal causes 1

• For macrocytic anemia (MCV > 100 fL):

  • Vitamin B12 levels
  • Serum folate levels 1

Additional Specialized Tests

• Vitamin B12 and folate levels should be measured when macrocytic anemia is present or when deficiencies are suspected 2, 1

• C-reactive protein or other inflammatory markers help distinguish between iron deficiency anemia and anemia of chronic disease 1

• For suspected hemolysis:

  • Lactate dehydrogenase (LDH)
  • Haptoglobin
  • Bilirubin 1

Common Pitfalls in Anemia Diagnosis

• Relying solely on hemoglobin and hematocrit can miss early iron deficiency, as these parameters decrease only in severe iron depletion 3

• Normal MCV does not rule out iron deficiency, as early iron deficiency can present with normal MCV but elevated red cell distribution width (RDW) 1, 3

• Serum ferritin is an acute phase reactant and may be falsely elevated in inflammatory conditions, potentially masking iron deficiency 1

• Failure to measure reticulocyte count can lead to misclassification of the anemia mechanism (production vs. destruction/loss) 1, 4

Diagnostic Algorithm

1. Start with CBC with red cell indices and reticulocyte count 2, 1
2. Classify anemia based on MCV:
   • Microcytic: Prioritize iron studies
   • Normocytic: Evaluate reticulocyte count, inflammatory markers
   • Macrocytic: Test for B12 and folate deficiencies 1
3. Assess iron status with ferritin and transferrin saturation 2, 1
4. If diagnosis remains unclear after initial testing, consider:
   • Bone marrow examination
   • Hemolysis workup
   • Specialized tests for rare causes 1, 4

Special Considerations

• In pregnancy, anemia is defined as hemoglobin <11.0 g/dL in the first trimester and <10.5 g/dL in later trimesters 5

• In chronic kidney disease, additional testing for erythropoietin deficiency may be needed 2, 1

• When inflammation is present, traditional cutoffs for ferritin may not apply; higher thresholds (e.g., <100 μg/L) may be needed to diagnose iron deficiency 1