What laboratory tests should be ordered for a patient with anemia?

Laboratory Workup for Anemia

Order a complete blood count (CBC) with red cell indices (MCV, MCH), serum ferritin, and consider additional tests based on the MCV pattern to determine the underlying cause.

Initial Essential Tests

Start with these core laboratory tests for any patient with suspected anemia:

• Complete Blood Count (CBC) with red cell indices including:

  • Hemoglobin (Hb) - defines anemia if <13 g/dL in men or <12 g/dL in women 1, 2
  • Mean Corpuscular Volume (MCV) - classifies anemia type
  • Mean Corpuscular Hemoglobin (MCH) - more reliable than MCV for iron deficiency 1

• Serum Ferritin - the most specific test for iron deficiency 1, 3

  • <15 μg/L is highly specific for iron deficiency (specificity 0.99)
  • <45 μg/L warrants investigation, especially with inflammation 1, 2
  • Note: Ferritin is an acute phase reactant and may be falsely elevated with inflammation, chronic kidney disease, or liver disease 1, 2

• Reticulocyte Count - distinguishes between production vs. destruction/loss 3, 4

Algorithm Based on MCV Classification

For Microcytic Anemia (Low MCV)

Order these additional tests:

• Iron panel (if not already done):

  • Serum iron
  • Total iron-binding capacity (TIBC)
  • Transferrin saturation 3, 5

• Hemoglobin electrophoresis - if microcytosis with normal iron studies, particularly in patients of Mediterranean, African, or Southeast Asian descent to rule out thalassemia 1

For Macrocytic Anemia (High MCV)

Order:

• Vitamin B12 level 3, 5
• Folate level 3, 5
• Consider methylmalonic acid or homocysteine if B12 deficiency suspected but levels borderline 6

For Normocytic Anemia (Normal MCV)

Order:

• Peripheral blood smear 3, 4
• Iron studies (ferritin, iron, TIBC, transferrin saturation)
• Lactate dehydrogenase (LDH) 3
• Haptoglobin 3
• Bilirubin (total and indirect) 3
• Consider renal function tests (creatinine, BUN) to evaluate for chronic kidney disease 7

Additional Considerations for Iron Deficiency Anemia

Once iron deficiency anemia is confirmed (Hb <13 g/dL in men or <12 g/dL in women AND ferritin <45 ng/mL), perform non-invasive testing:

• H. pylori testing (stool antigen or urea breath test) 2
• Celiac disease serologies (tissue transglutaminase IgA with total IgA) 2
• Fecal occult blood test 4

Critical Pitfalls to Avoid

Ferritin interpretation errors: The most common mistake is using ferritin <15 μg/L as the only threshold. In patients with chronic inflammation, chronic kidney disease, or liver disease, iron deficiency can exist with ferritin levels up to 100-150 μg/L. Use the <45 μg/L cutoff in these contexts 1, 2.

Missing thalassemia: Don't pursue extensive GI workup in patients with microcytic anemia and normal iron studies without first checking hemoglobin electrophoresis, especially in appropriate ethnic populations 1.

Over-reliance on MCV alone: MCH is actually more sensitive and reliable for detecting iron deficiency than MCV, as it's less affected by storage conditions and laboratory variation 1.

What NOT to Routinely Order

• Avoid routine endoscopic biopsies for celiac disease and H. pylori if non-invasive testing is negative 2
• Don't order serum transferrin receptor (sTfR) as a first-line test - most hospitals don't offer it and it's mainly useful in complex cases with chronic disease 1