What are the basic investigations for diagnosing anemia?

Basic Investigations for Anemia

The initial workup for anemia should include a complete blood count (CBC) with red cell indices, absolute reticulocyte count, serum ferritin, transferrin saturation (TSAT), and vitamin B12 and folate levels. 1, 2

Essential First-Line Tests

Complete Blood Count with Indices

• Hemoglobin concentration is the preferred measure over hematocrit due to better reproducibility across laboratories and lack of influence from sample storage time or patient glucose levels 2
• Mean corpuscular volume (MCV) classifies anemia into three categories: microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) 1, 2
• Red cell distribution width (RDW) indicates variation in red cell size; elevated RDW with normal MCV can suggest early iron deficiency or mixed nutritional deficiencies 1
• White blood cell count with differential and platelet count are essential to identify abnormalities in multiple cell lines, which warrant hematology consultation 2

Reticulocyte Count

• Absolute reticulocyte count assesses bone marrow response to anemia 3, 1, 2
• A low or normal reticulocyte count indicates impaired erythropoiesis (production problem) 1
• An elevated reticulocyte count suggests increased red cell production in response to hemolysis or blood loss 1, 2

Iron Studies

• Serum ferritin is 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) values <15-16% support iron deficiency and are less affected by inflammation than ferritin 1, 2
• Total iron-binding capacity provides additional context for iron status 3

Vitamin Levels

• Vitamin B12 and folate levels are essential for evaluating macrocytic anemia and should be obtained in the initial workup 3, 1, 2

Peripheral Blood Smear

• Microscopic examination of red cell morphology provides critical diagnostic information 3, 4
• In some cases, bone marrow examination may be necessary when the initial workup is unrevealing or when additional cytopenias are present 3, 2

Rationale for Each Test

Why MCV Matters

• Microcytic anemia (MCV <80 fL) most commonly indicates iron deficiency anemia, the most prevalent cause of anemia globally 1, 2
• Normocytic anemia (MCV 80-100 fL) may indicate hemorrhage, hemolysis, or anemia of chronic inflammation 1, 2
• Macrocytic anemia (MCV >100 fL) suggests vitamin B12 or folate deficiency 1, 2

Why Ferritin and TSAT Are Critical

• Ferritin <30 μg/L confirms iron deficiency without inflammation 1, 2
• Important caveat: Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease, requiring clinical context for interpretation 1, 2
• TSAT <30% combined with ferritin <500 ng/mL indicates iron deficiency even in the presence of inflammation 3

Why Reticulocyte Count Is Essential

• Distinguishes between production defects (low reticulocyte count) and destruction/loss problems (high reticulocyte count) 1, 2
• Guides whether to investigate bone marrow failure versus hemolysis or bleeding 3, 2

Additional Context-Specific Tests

When Iron Deficiency Is Confirmed

• Investigate the underlying cause: gastrointestinal bleeding in adult men and postmenopausal women, menstrual losses in premenopausal women 1, 2
• Thorough drug exposure history to identify NSAID use, aspirin, or anticoagulants 3

When Anemia of Chronic Disease Is Suspected

• C-reactive protein can help assess the contribution of inflammation to elevated ferritin 2
• Elevated ferritin with low TSAT suggests anemia of chronic inflammation 2

When Hemolysis Is Suspected

• Haptoglobin, lactate dehydrogenase (LDH), and bilirubin are necessary 1
• Direct antiglobulin testing (Coombs test) for patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or history of autoimmune disease 3

Additional Investigations in Specific Contexts

• Thyroid-stimulating hormone (TSH) when indicated 3
• Hemoglobin electrophoresis if hemoglobinopathies like thalassemia trait are suspected, particularly in patients with appropriate ethnic background 1
• Assessment for occult blood loss and renal insufficiency in cancer patients receiving chemotherapy 3

Common Pitfalls to Avoid

• Do not accept ferritin alone in patients with inflammation; use TSAT to confirm iron deficiency 1, 2
• Do not stop at finding one abnormality in the upper GI tract (like peptic ulcer or esophagitis) without investigating the colon, as dual pathology occurs in 10-15% of patients 3
• Do not overlook dietary history, but do not presume borderline deficient diets as the sole cause without full investigation 3
• Do not delay hematology consultation when abnormalities in two or more cell lines are present 2