What laboratory tests are needed to diagnose anemia?

Laboratory Tests for Diagnosing Anemia

Start with a complete blood count (CBC) including hemoglobin, red cell indices (MCV, MCH, MCHC), white blood cell count with differential, platelet count, and absolute reticulocyte count, followed immediately by iron studies (serum ferritin and transferrin saturation) and vitamin B12 and folate levels. 1, 2

Essential Initial Laboratory Panel

Hemoglobin measurement is the cornerstone test and is preferred over hematocrit because it demonstrates better reproducibility across laboratories, has lower within-assessment and between-assessment coefficients of variation, and is not affected by sample storage time or patient-specific variables like serum glucose. 3

The complete initial workup must include:

• Complete blood count (CBC) with white blood cells, hemoglobin, platelets, and red cell indices (MCV, MCH, MCHC, RDW) to assess bone marrow function and characterize the anemia 3, 1

• Absolute reticulocyte count to evaluate bone marrow response to anemia—a low count indicates impaired red cell production while an elevated count suggests increased production from hemorrhage or hemolysis 3, 1, 2

• Serum ferritin as the single most useful marker for iron stores, with levels <30 μg/L confirming iron deficiency in the absence of inflammation 1, 2

• Transferrin saturation (TSAT) with values <15-16% supporting iron deficiency; this marker is less affected by inflammation than ferritin 1, 2

• Vitamin B12 and folate levels to evaluate for macrocytic anemia and nutritional deficiencies 3, 1, 2

Interpreting Red Cell Indices for Anemia Classification

The MCV guides your diagnostic approach algorithmically:

• Microcytic anemia (MCV < 80 fL): Most commonly indicates iron deficiency anemia, which is the most prevalent cause of anemia globally; other causes include thalassemia, anemia of chronic disease, and sideroblastic anemia 3, 1, 2

• Normocytic anemia (MCV 80-100 fL): May indicate hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency—the reticulocyte count becomes the key follow-up test 3, 1, 2

• Macrocytic anemia (MCV > 100 fL): Most commonly suggests vitamin B12 or folate deficiency; non-megaloblastic causes include alcoholism, myelodysplastic syndrome, and certain drugs like hydroxyurea 3, 1, 2

Critical Additional Assessments

If abnormalities appear in two or more cell lines (white cells, red cells, or platelets), immediately consult hematology as this suggests bone marrow dysfunction requiring specialized evaluation. 3, 1

Important Caveats for Iron Studies

• Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease, requiring clinical context for accurate interpretation 1, 2

• In patients with elevated ferritin despite suspected iron deficiency, measure C-reactive protein to assess the contribution of inflammation to the elevated ferritin level 3, 1

• MCH (mean corpuscular hemoglobin) is more reliable than MCHC for detecting iron deficiency because it is less dependent on storage conditions and counting equipment 2

When to Investigate Further

• In adult men and postmenopausal women with confirmed iron deficiency, investigate for gastrointestinal bleeding as the underlying cause 3, 1, 2

• If the initial workup is unrevealing or additional cytopenias are present, consider bone marrow aspiration and biopsy 1

• For anemia of chronic inflammation (elevated ferritin with low TSAT), treat the underlying condition; erythropoietin therapy may be considered in specific situations such as chronic kidney disease 1, 2

Practical Laboratory Ordering Strategy

Order these tests simultaneously at the initial visit to avoid delays:

• CBC with differential, platelets, and red cell indices 1, 2
• Absolute reticulocyte count 1, 2
• Serum ferritin 1, 2
• Transferrin saturation (or serum iron and total iron-binding capacity) 1, 2
• Vitamin B12 level 1, 2
• Folate level 1, 2

This comprehensive initial panel allows you to characterize the anemia morphologically and kinetically, identify the most common causes (iron deficiency, vitamin deficiencies, chronic disease), and determine the bone marrow's response—all from a single blood draw. 1, 2