What labs are used to diagnose and manage anemia?

Laboratory Evaluation for Anemia

Begin with a complete blood count (CBC) including hemoglobin, white blood cells, and platelets, as hemoglobin is the most reproducible measure across laboratories and should be used to define anemia rather than hematocrit. 1, 2

Initial Diagnostic Tests

Essential First-Line Labs

• Hemoglobin concentration is preferred over hematocrit because it has lower variability between laboratories and is not affected by sample storage time or patient variables like serum glucose 1

  • Anemia is defined as hemoglobin <12 g/dL in women and <13 g/dL in men 2

• Complete blood count (CBC) with differential assesses bone marrow function across all cell lines 1

  • Abnormalities in two or more cell lines warrant hematology consultation 1

• Mean corpuscular volume (MCV) classifies anemia morphologically 1, 2

  • MCV <80 fL indicates microcytic anemia
  • MCV 80-100 fL indicates normocytic anemia
  • MCV >100 fL indicates macrocytic anemia 2

• Red cell distribution width (RDW) identifies mixed deficiencies when MCV appears normal 1, 2

  • Elevated RDW suggests coexisting iron deficiency even with normal MCV 1, 2

• Reticulocyte count (absolute or reticulocyte index) evaluates bone marrow response to anemia 1, 2

  • Low reticulocyte count indicates production defect (deficiencies, bone marrow failure) 2
  • Elevated reticulocytes suggest hemolysis or acute blood loss 2

Iron Status Assessment

Core Iron Studies

Serum ferritin is the most powerful test for iron deficiency and the best surrogate marker for tissue iron stores. 1

• Without inflammation: Ferritin <30 μg/L indicates iron deficiency 1, 2

  • In some populations, <25 ng/mL in males and <11 ng/mL in females may be used 1
  • Ferritin <12 μg/dL is diagnostic of iron deficiency 1

• With inflammation present: Ferritin up to 100 μg/L may still indicate iron deficiency 1, 2

  • Ferritin >100 μg/L makes iron deficiency unlikely 1
  • Ferritin acts as an acute-phase reactant and can be falsely elevated in inflammation, malignancy, or hepatic disease 1

• Transferrin saturation represents iron available for erythropoiesis 1, 2

  • <20% indicates functional or absolute iron deficiency 2
  • <30% may support diagnosis when ferritin is equivocal 1
  • More reliable than ferritin in chronic kidney disease patients because it is less affected by inflammation 1

Inflammatory Markers

• C-reactive protein (CRP) should be measured when interpreting iron studies to assess inflammatory contribution 1, 2
  • Helps distinguish between iron deficiency anemia and anemia of chronic disease 1

Additional Nutritional Studies

When low MCV or inadequate reticulocyte response is present despite normal iron studies:

• Vitamin B12 levels to evaluate for macrocytic anemia or combined deficiency 1
• Folate levels to assess for deficiency causing macrocytic anemia 1

Hemolysis Evaluation

When reticulocyte count is elevated, assess for hemolysis:

• Haptoglobin (decreased in hemolysis) 1
• Lactate dehydrogenase (LDH) (elevated in hemolysis) 1
• Indirect bilirubin (elevated in hemolysis) 1

Common Pitfalls to Avoid

• Do not rely on MCV alone for classification, as coexisting deficiencies can neutralize MCV changes and result in falsely normal values 1, 2

  • Always check RDW to identify mixed deficiencies 1, 2

• Do not interpret ferritin without assessing inflammatory status, as inflammation falsely elevates ferritin levels 1, 2

  • Always measure CRP when ferritin is 30-100 μg/L 1, 2

• Do not assume normal hemoglobin/hematocrit excludes iron deficiency, as these are late markers that decrease only with severe depletion 1, 3

  • Iron studies should accompany CBC to avoid missing early iron deficiency 3

• Do not overlook gastrointestinal bleeding when iron deficiency is found in men or postmenopausal women not on erythropoietic agents 1

  • This warrants careful GI assessment 1

Specialized Tests (When Available)

• Percent hypochromic red blood cells (PHRBC) and reticulocyte hemoglobin content (CHr) may identify functional iron deficiency with greater sensitivity than ferritin and transferrin saturation 1

  • Not widely available and require specialized equipment 1
  • PHRBC is time-sensitive and less useful if samples are shipped 1

• Soluble transferrin receptor may help distinguish iron deficiency anemia from anemia of chronic disease 2