What labs are used to diagnose anemia?

Laboratory Diagnosis of Anemia

Initial Diagnostic Test

A complete blood count (CBC) with hemoglobin measurement is the essential first test for diagnosing anemia, with hemoglobin <12 g/dL in women and <13 g/dL in men defining anemia. 1 Hemoglobin is preferred over hematocrit because it is more reproducible across laboratories and not affected by sample storage time or patient variables like serum glucose. 2

Core Laboratory Panel for Anemia Diagnosis

Complete Blood Count with Indices

• Hemoglobin and hematocrit detect anemia but are late indicators that only decrease with severe iron depletion. 2, 3
• Mean corpuscular volume (MCV) classifies anemia as microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL). 2, 1
• Red cell distribution width (RDW) >14% with microcytosis strongly suggests iron deficiency anemia and indicates coexisting deficiencies when elevated. 1, 4
• White blood cell and platelet counts assess bone marrow function; abnormalities in two or more cell lines warrant hematology consultation. 2

Reticulocyte Count

• Reticulocyte index distinguishes production defects (low/normal count suggesting iron, B12, or folate deficiency) from hemolysis or blood loss (elevated count). 2, 1
• A normal reticulocyte index ranges between 1.0 and 2.0. 2

Peripheral Blood Smear

• Visual review confirms RBC size, shape, and color, providing critical morphologic information that indices alone cannot capture. 2, 5

Iron Status Assessment

First-Line Iron Studies

• Serum ferritin is the primary diagnostic test for iron deficiency, with <30 μg/L indicating iron deficiency in non-inflammatory states. 1, 4
• In patients with inflammation, malignancy, or hepatic disease, use a higher threshold of ferritin <100 μg/L to diagnose iron deficiency. 4
• Transferrin saturation <20% indicates functional or absolute iron deficiency and is less affected by inflammation than ferritin. 2, 1

Interpreting Iron Studies with Inflammation

• C-reactive protein (CRP) should be measured when ferritin is 30-100 μg/L to assess whether inflammation is elevating ferritin levels. 1
• Ferritin acts as an acute-phase reactant and may be elevated irrespective of true iron stores in inflammatory conditions. 2

Advanced Iron Markers (When Available)

• Soluble transferrin receptor helps distinguish iron deficiency anemia from anemia of chronic disease. 1
• Percent hypochromic red blood cells (PHRBC) and reticulocyte hemoglobin content (CHr) have sensitivities and specificities equal to or greater than ferritin and transferrin saturation but require specialized equipment. 2

Vitamin Deficiency Testing

Macrocytic Anemia Workup

• Serum vitamin B12 and folate levels are essential when MCV >100 fL. 2, 6
• Methylmalonic acid (MMA) is a sensitive early marker for B12 deficiency, often elevated before clinical symptoms appear. 6
• Homocysteine is also elevated in B12 deficiency, providing additional confirmatory evidence. 6

Additional Testing Based on Clinical Context

Celiac Disease Screening

• Celiac serology should be performed in all patients with confirmed iron deficiency anemia, as 2-3% have celiac disease. 4

Hemoglobinopathy Evaluation

• Hemoglobin electrophoresis is indicated when microcytosis is present with normal or elevated ferritin, particularly in patients of appropriate ethnic background (Mediterranean, African, Southeast Asian descent). 4

Chronic Disease Assessment

• In patients with normocytic anemia and elevated ferritin (>100 μg/L) with low transferrin saturation (<20%), consider anemia of chronic disease. 1

Critical Pitfalls to Avoid

• Do not rely on CBC alone without iron studies. Normal hemoglobin and hematocrit do not exclude iron depletion, as these decrease only with severe deficiency. 3
• Do not interpret ferritin in isolation. A "normal" ferritin (30-100 μg/L) may still represent iron deficiency in the presence of inflammation. 4
• Do not assume normal MCV excludes iron deficiency. Coexisting conditions (e.g., combined iron and B12 deficiency) may neutralize MCV changes, but RDW will be elevated. 1
• Do not accept dietary history alone as the cause. In men and postmenopausal women with iron deficiency, gastrointestinal bleeding from lesions is found in 62% of cases. 2, 4
• Do not skip reticulocyte count. This distinguishes production defects from hemolysis/blood loss and guides further workup. 2, 1