What tests are used to diagnose anemia?

Diagnostic Tests for Anemia

The complete blood count (CBC) is the primary test for diagnosing anemia, with hemoglobin measurement being preferred over hematocrit due to its greater reproducibility across laboratories and lower susceptibility to storage time and patient-specific variables. 1

Initial Diagnostic Approach

Complete Blood Count (CBC)

• Hemoglobin concentration: Primary measure for diagnosing anemia 2, 1
• Red blood cell (RBC) count: Helps confirm anemia diagnosis
• Hematocrit: Less reliable than hemoglobin but still useful 2
• Red cell indices:
  • Mean Corpuscular Volume (MCV): Helps classify anemia as microcytic, normocytic, or macrocytic
  • Mean Corpuscular Hemoglobin (MCH)
  • Mean Corpuscular Hemoglobin Concentration (MCHC)
  • Red Cell Distribution Width (RDW): Indicates variation in red cell size

Reticulocyte Count

• Evaluates bone marrow response to anemia
• Low count suggests defective red cell production or insufficient iron
• Can be expressed as absolute count or reticulocyte index (adjusted for degree of anemia) 2

Iron Status Assessment

Iron deficiency is a common cause of anemia and requires specific testing:

• Serum ferritin: Primary marker for tissue iron stores 2, 1

  • <15 μg/L: Highly specific for iron deficiency (specificity 0.99) 1
  • <30 μg/L: Indicates absent/low iron stores in non-inflammatory states 1
  • <45 μg/L: Optimal cutoff for clinical practice (specificity 0.92) 1
  • Note: Ferritin is an acute-phase reactant and may be elevated in inflammation regardless of iron status 2

• Transferrin saturation: More reliable marker of iron availability for erythropoiesis

  • <20% suggests iron deficiency 1
  • Less affected by inflammation than ferritin 2

• Total Iron Binding Capacity (TIBC): Increased in iron deficiency 1

Additional Tests for Specific Causes

• Vitamin B12 and folate levels: To assess for deficiency-related anemia 1

  • Consider methylmalonic acid and homocysteine if B12 deficiency is suspected despite normal B12 levels

• Inflammatory markers: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)

  • Help distinguish anemia of chronic disease from iron deficiency anemia 1
  • May be useful when evaluating elevated ferritin levels 2

• Peripheral blood smear: Evaluates red cell morphology and can help identify specific causes 1

• Additional tests when indicated:

  • Liver function tests
  • Thyroid function tests
  • Kidney function tests (especially in suspected chronic kidney disease)
  • Hemoglobin electrophoresis (for suspected hemoglobinopathies)

Special Considerations

Interpreting CBC Parameters

• Low MCV (<84.10 fL) has good discriminating power for iron deficiency anemia (AUC 0.77) 3
• Low MCHC (<337.5 g/L) is also a good discriminator for iron deficiency anemia (AUC 0.80) 3
• CBC parameters alone have limited utility for diagnosing iron deficiency without anemia 3

Chronic Kidney Disease

• Patients with CKD (GFR <60 mL/min/1.73 m²) require careful evaluation due to decreased erythropoietin production 1
• Anemia in CKD is typically normochromic and normocytic 2
• Finding iron deficiency in non-dialysis CKD patients without obvious causes should prompt evaluation for gastrointestinal bleeding 2

Common Pitfalls to Avoid

1. Relying solely on hematocrit: Hemoglobin is more reliable and less affected by storage time and patient variables like serum glucose 2

2. Misinterpreting ferritin in inflammatory states: Always consider inflammation when interpreting ferritin levels, as they may be falsely elevated 2, 1

3. Failing to investigate abnormalities in multiple cell lines: Abnormalities in two or more cell lines (white blood cells, hemoglobin, platelets) warrant careful evaluation and possible hematology consultation 2

4. Not considering timing of sample collection: Tests like percent hypochromic red blood cells (PHRBC) are time-sensitive and less useful if samples are shipped to central labs 2

5. Overlooking the need for comprehensive testing: CBC alone may not be sufficient; iron studies, vitamin levels, and other tests are often needed for complete evaluation 1