What laboratory tests are used to diagnose iron deficiency anemia?

Laboratory Tests for Diagnosing Iron Deficiency Anemia

No single test is universally accepted for diagnosing iron deficiency anemia; a combination of hematological and biochemical tests is required for accurate diagnosis, with serum ferritin being the most powerful diagnostic test when combined with other parameters. 1

Initial Screening Tests

• Hemoglobin concentration and hematocrit are the most commonly used initial screening tests due to their low cost, ease of performance, and rapid results 2
• Complete Blood Count (CBC) is the recommended first step in evaluating for iron deficiency anemia 1, 3
• Hemoglobin is preferred over hematocrit as it is more reproducible across laboratories and is not affected by storage time or patient-specific variables like serum glucose 2
• These tests are late indicators of iron deficiency but essential for determining iron-deficiency anemia 2

Red Cell Indices

• Mean Corpuscular Volume (MCV) - typically low in iron deficiency (microcytosis) 2, 3
• Mean Corpuscular Hemoglobin (MCH) - reduced in iron deficiency 3
• Mean Corpuscular Hemoglobin Concentration (MCHC) - reduced in iron deficiency 3
• Red Cell Distribution Width (RDW) - elevated (>14.0%) with microcytosis strongly suggests iron deficiency anemia 1

Biochemical Tests for Iron Status

• Serum ferritin - the most sensitive test for iron stores; levels <25 ng/ml in males and <11 ng/ml in females indicate insufficient iron stores 2, 1
• Transferrin saturation - represents iron available to bone marrow for erythropoiesis; less affected by inflammation than ferritin 2
• Erythrocyte protoporphyrin concentration - detects early changes in iron status 2

Advanced or Specialized Tests

• Reticulocyte hemoglobin content (CHr) - early marker of iron-deficient erythropoiesis; increases within days of iron therapy initiation 4
• Percent hypochromic red blood cells (PHRBC) - can identify functional iron deficiency but is time-sensitive and requires specialized equipment 2
• Serum transferrin receptor levels - less affected by inflammation and chronic disease 5

Diagnostic Algorithm

1. Start with CBC including hemoglobin, hematocrit, and red cell indices 1, 3
2. If anemia is present (hemoglobin below lower limit of normal), proceed with iron studies 6
3. Measure serum ferritin as the primary marker of iron stores 1
4. Add transferrin saturation to improve diagnostic accuracy 2
5. In cases of inflammation or chronic disease, use higher ferritin threshold (<100 μg/L) to diagnose iron deficiency 1

Special Considerations

• In inflammatory states, ferritin may be falsely elevated as an acute phase reactant 1
• For cases with ferritin levels between 46-99 ng/mL, additional tests like total iron-binding capacity, transferrin saturation, and serum transferrin receptor levels may be necessary 5
• Bone marrow examination remains the gold standard but is invasive, painful, and costly 4
• In patients with chronic kidney disease, interpretation of ferritin levels is difficult due to its role as an acute-phase reactant 2

Common Pitfalls to Avoid

• Relying solely on hemoglobin and hematocrit for diagnosis, as they are late indicators of iron deficiency 2
• Failing to consider inflammation when interpreting ferritin levels 1
• Not recognizing that iron deficiency anemia in men and postmenopausal women often indicates gastrointestinal bleeding that requires further investigation 2
• Assuming anemia in elderly patients is due to iron deficiency when chronic disease or inflammatory conditions are common causes 2

By following this comprehensive approach to laboratory testing, clinicians can accurately diagnose iron deficiency anemia and initiate appropriate treatment to improve patient outcomes.