Diagnostic Laboratory Tests for Anemia
The essential laboratory tests for diagnosing anemia include a complete blood count (CBC) with hemoglobin measurement, reticulocyte count, iron studies (serum ferritin and transferrin saturation), and assessment of red cell morphology. 1
Initial Diagnostic Approach
Primary Laboratory Tests
- Hemoglobin measurement: Preferred over hematocrit due to better reproducibility across laboratories and less susceptibility to storage time or patient variables like serum glucose 1
- Complete Blood Count (CBC) including:
- White blood cell count
- Hemoglobin level
- Platelet count
- Red cell indices (MCV, MCH, MCHC)
- Red blood cell distribution width (RDW)
- Reticulocyte count: Evaluates bone marrow response to anemia; can be reported as absolute count or reticulocyte index (adjusted for degree of anemia) 1
Iron Status Assessment
- Serum ferritin: Surrogate marker for tissue iron stores
- Transferrin saturation: Represents iron available for erythropoiesis
- Mean corpuscular volume (MCV): Late marker of iron deficiency 1
Diagnostic Algorithm Based on MCV Classification
Microcytic Anemia (MCV < 80 fL)
- Iron studies:
- Serum ferritin (<30 μg/L indicates iron deficiency)
- Transferrin saturation (low in iron deficiency)
- RDW (elevated in iron deficiency)
- Hemoglobin electrophoresis: If thalassemia is suspected 2
Normocytic Anemia (MCV 80-100 fL)
- Reticulocyte count:
- Additional tests if hemolysis suspected:
- Serum haptoglobin (decreased)
- Lactate dehydrogenase (elevated)
- Bilirubin (elevated) 2
Macrocytic Anemia (MCV > 100 fL)
- Vitamin B12 and folate levels
- Liver function tests
- Thyroid function tests
- Reticulocyte count 4
Advanced or Specialized Testing
- Soluble transferrin receptor (sTfR): Helps differentiate between anemia of chronic disease and iron deficiency 2
- Inflammatory markers (CRP, ESR): To assess for underlying inflammation that may affect iron parameters 2
- Percent hypochromic red blood cells (PHRBC) and content of hemoglobin in red blood cells (CHr): May have better sensitivity/specificity than ferritin and transferrin saturation for functional iron deficiency, but less widely available 1
Important Clinical Considerations
- Abnormalities in two or more cell lines (white blood cells, red blood cells, platelets) warrant hematology consultation 1
- In patients with chronic kidney disease, ferritin interpretation is complicated by its role as an acute-phase reactant 1
- Ferritin may appear normal in iron deficiency with concurrent inflammation; values <100 μg/L should be considered suspicious in inflammatory states 2
- CBC parameters alone without iron studies may miss early iron depletion 5
Diagnostic Cut-off Values
- Iron deficiency: Ferritin <30 μg/L (more stringent values: <25 ng/ml in males, <11 ng/ml in females) 1, 6
- Iron deficiency anemia: Ferritin <30 μg/L with hemoglobin <120 g/L in women 6
- CBC parameters for iron deficiency anemia 6:
- RBC count: <4.04 × 10¹²/L
- MCV: <84.10 fL
- MCHC: <337.5 g/L
- MCH: <29.15 pg
- Hematocrit: <35.5%
Remember that a single laboratory value should not be used in isolation to diagnose anemia, and the pattern of abnormalities across multiple parameters provides the most accurate diagnosis.