What labs are drawn to diagnose anemia?

Laboratory Workup for Diagnosing Anemia

Start with a complete blood count (CBC) with hemoglobin measurement, as hemoglobin is more reproducible than hematocrit and serves as the primary diagnostic criterion for anemia. 1

Initial Essential Tests

Core Screening Panel

• Hemoglobin concentration: The gold standard for diagnosing anemia—more reliable than hematocrit because it's unaffected by sample storage time or patient variables like serum glucose 1
• Complete blood count (CBC) with differential: Assesses all three cell lines (white blood cells, hemoglobin, platelets) to evaluate bone marrow function 1
• Mean corpuscular volume (MCV): Classifies anemia as microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) 1
• Peripheral blood smear: Visual review is critical to confirm red blood cell size, shape, and color 1

Iron Status Assessment

• Serum ferritin: The primary test for iron deficiency, with <12 μg/dL being diagnostic in the absence of inflammation 2
  • In patients with inflammation, malignancy, or hepatic disease, use a higher threshold of <100 μg/L 2
  • Without inflammation: ferritin <30 μg/L indicates iron deficiency 1
  • With inflammation: ferritin up to 100 μg/L may still represent iron deficiency 1
• Transferrin saturation: More reliable than ferritin in inflammatory states, as it's less affected by inflammation 1
  • <15% with ferritin <30 ng/mL indicates absolute iron deficiency 1
  • <20% with ferritin >100 μg/L suggests anemia of chronic disease 1
  • <30% helps confirm diagnosis when ferritin is equivocal 2
• C-reactive protein (CRP): Essential to interpret ferritin levels, as ferritin acts as an acute-phase reactant 1

Secondary Tests Based on Initial Results

Bone Marrow Response Evaluation

• Reticulocyte count (absolute or reticulocyte index): Evaluates bone marrow's response to anemia 1
  • Low count: suggests decreased RBC production (iron deficiency, B12/folate deficiency, bone marrow dysfunction) 1
  • High count: indicates blood loss or hemolysis 1
  • Normal reticulocyte index ranges 1.0-2.0 1

Additional Red Cell Parameters

• Red cell distribution width (RDW): Elevated RDW >14.0% with microcytosis strongly suggests iron deficiency anemia 2
  • High RDW indicates mixed cell sizes, helpful when microcytosis and macrocytosis coexist 1

Extended Workup When Cause Unclear

• Vitamin B12 and folate levels: For macrocytic anemia or when other tests are inconclusive 1
• Hemoglobin electrophoresis: When microcytosis is present in patients of appropriate ethnic background to rule out thalassemia 2
• Haptoglobin and lactate dehydrogenase: If hemolysis is suspected 1
• Celiac disease screening (tissue transglutaminase antibody): 2-3% of iron deficiency anemia patients have celiac disease 2

Algorithmic Approach by MCV Classification

Microcytic Anemia (MCV <80 fL)

1. Check ferritin and transferrin saturation first 1
2. If iron studies suggest iron deficiency, proceed with iron supplementation 2
3. If iron studies are normal, consider hemoglobin electrophoresis for thalassemia 2

Normocytic Anemia (MCV 80-100 fL)

1. Check reticulocyte count immediately 1
2. Low reticulocyte count: evaluate for chronic disease, renal insufficiency, or bone marrow failure 1
3. High reticulocyte count: investigate for hemorrhage or hemolysis 1

Macrocytic Anemia (MCV >100 fL)

1. Measure vitamin B12 and folate levels 1
2. Consider medication review (hydroxyurea, diphenytoin) 1
3. Evaluate for myelodysplastic syndrome if other causes excluded 1

Critical Pitfalls to Avoid

• Don't rely solely on hemoglobin/hematocrit: These are late indicators of iron deficiency and miss early stages 1, 2
• Don't assume dietary insufficiency alone: Complete the full diagnostic workup even with positive dietary history 2
• Don't overlook inflammation: Normal ferritin doesn't exclude iron deficiency in inflammatory conditions—use the 100 μg/L threshold 2
• Don't skip celiac screening: This is frequently missed even without GI symptoms 2
• Don't accept minor upper GI findings alone: Complete both upper and lower GI evaluation in appropriate patients 2
• Avoid "milking" the finger: Excessive squeezing during capillary blood sampling contaminates with tissue fluid, causing falsely low readings 1

Special Population Considerations

Chronic Kidney Disease Patients

• Predialysis hemoglobin measurements are preferred 1
• Ferritin interpretation is complicated by inflammation—consider C-reactive protein measurement 1
• Insufficient erythropoietin production is the most common cause of low reticulocyte response when iron, folate, and B12 are replete 1

Inflammatory Bowel Disease Patients

• Screen all patients with full blood count, serum ferritin, and CRP 1
• Distinguish between iron deficiency anemia and anemia of chronic disease using the ferritin thresholds adjusted for inflammation 1