What laboratory tests are included in a comprehensive anemia profile?

Anemia Profile Laboratory Tests

A comprehensive anemia profile should include a complete blood count (CBC) with red cell indices (MCV, MCH, RDW), reticulocyte count, serum ferritin, transferrin saturation (calculated from serum iron and TIBC), and vitamin B12 and folate levels. 1

Core Hematologic Tests

Complete Blood Count with Red Cell Indices

• Hemoglobin and hematocrit serve as screening tests but are late indicators of deficiency states 1
• Mean corpuscular volume (MCV) measures average red blood cell size (normal 80-100 fL) and is essential for classifying anemia as microcytic, normocytic, or macrocytic 1
• Red cell distribution width (RDW) is critical for detecting mixed deficiencies, with elevated RDW >14.0% suggesting iron deficiency anemia 1
• Mean corpuscular hemoglobin (MCH) provides sensitive indication of iron deficiency, with low levels indicating iron depletion 1

Reticulocyte Count

• Reticulocyte count distinguishes between production defects versus hemolysis or blood loss, with elevated reticulocytes indicating increased red blood cell production 1
• This test serves as a useful screen for hemolytic processes or acute blood loss 2

Peripheral Blood Smear

• Review of peripheral blood smear is recommended as many anemias have characteristic red cell morphology that guides diagnosis 3, 2
• In some cases, bone marrow examination may be needed 3

Iron Status Assessment

Primary Iron Tests

• Serum ferritin is the most powerful single test for diagnosing iron deficiency, with levels <30 μg/L indicating iron deficiency 1
• Transferrin saturation represents iron available for erythropoiesis, with <20% indicating functional or absolute iron deficiency 1
• Serum iron and total iron-binding capacity (TIBC) are measured together to calculate transferrin saturation, with low serum iron and high TIBC indicating iron deficiency 1

Critical Interpretation Caveat

• Ferritin is an acute-phase reactant and may be falsely elevated in inflammatory conditions, requiring a higher threshold (<100 μg/L) to diagnose iron deficiency in these patients 1
• C-reactive protein (CRP) should be measured alongside ferritin to assess for inflammation that could confound interpretation 1

Vitamin Deficiency Testing

Vitamin B12 and Folate

• Serum vitamin B12 and folate levels are essential components of the anemia profile 3, 1
• Methylmalonic acid (MMA) is a sensitive marker for B12 deficiency, often elevated early in the condition 4
• Homocysteine levels are also elevated in B12 deficiency, providing additional confirmatory evidence 4
• Unlike iron studies, inflammatory conditions do not significantly affect interpretation of B12 testing 4

Additional Investigations in Specific Contexts

When Baseline Tests Are Inconclusive

• Erythrocyte protoporphyrin concentration detects earlier changes in iron status than hemoglobin or hematocrit, with elevated levels indicating iron deficiency 1
• Soluble transferrin receptor (sTfR) may help distinguish iron deficiency anemia from anemia of chronic disease, particularly in patients with liver disease or inflammatory conditions 1
• Reticulocyte hemoglobin content (CHr) and percent hypochromic red blood cells (PHRBC) are specialized tests with high sensitivity and specificity for functional iron deficiency, though they require expensive equipment 1

Cancer-Specific Anemia Workup

• Thorough drug exposure history to identify chemotherapy-related causes 3
• Assessment of occult blood loss and renal insufficiency 3
• Baseline erythropoietin level 3
• Serum thyroid-stimulating hormone level where indicated 3
• Direct antiglobulin testing (Coombs test) for patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or history of autoimmune disease 3
• Hemoglobinopathy screening where indicated 3

Common Pitfalls to Avoid

• Do not rely solely on MCV for classification, as coexisting conditions (e.g., combined iron and B12 deficiency) may neutralize MCV changes 1
• Do not misinterpret ferritin without considering inflammatory status, as this leads to incorrect diagnosis in patients with chronic disease 1
• Do not fail to investigate underlying causes of deficiencies, particularly gastrointestinal bleeding in iron deficiency, which is found in 60-70% of patients with iron deficiency anemia referred for endoscopy 1, 5