What laboratory tests are used to diagnose iron deficiency anemia?

Laboratory Tests for Diagnosing Iron Deficiency Anemia

The most essential laboratory tests for diagnosing iron deficiency anemia include serum ferritin as the primary marker of iron stores, complete blood count (CBC), and transferrin saturation. 1

Initial Screening Tests

• Complete Blood Count (CBC) is the recommended first step in evaluating for iron deficiency anemia 1
• Hemoglobin concentration should be used to define anemia based on the lower limit of the normal range for the laboratory performing the test 2
• Red Cell Distribution Width (RDW) - elevated (>14.0%) with microcytosis strongly suggests iron deficiency anemia 1
• Microcytosis (low MCV) is characteristic of iron deficiency but may be absent in combined deficiencies or present in other conditions like thalassemia 2

Definitive Iron Status Tests

• Serum ferritin is the most powerful test for diagnosing iron deficiency 2, 1
  • Levels <12 μg/dl are diagnostic of iron deficiency 2
  • In males, levels <25 ng/ml and in females <11 ng/ml indicate insufficient iron stores 1
  • In inflammatory states, higher ferritin threshold (<100 μg/L) should be used to diagnose iron deficiency 1
• Transferrin saturation of <30% helps confirm the diagnosis 2
• Erythrocyte protoporphyrin concentration detects early changes in iron status 1

Diagnostic Algorithm

1. Start with CBC to identify anemia and assess red cell indices 1
2. Measure serum ferritin as the primary marker of iron stores 1
3. Add transferrin saturation to improve diagnostic accuracy 1
4. In cases with suspected inflammation or chronic disease:
   • Use higher ferritin threshold (<100 μg/L) to diagnose iron deficiency 2, 1
   • Consider additional tests like percent hypochromic red blood cells (PHRBC) 1

Advanced or Specialized Tests

• Bone marrow aspiration with iron staining is the definitive test for confirming true iron deficiency when other tests are inconclusive 2
• Serum transferrin binding receptor/ferritin ratio shows promise in distinguishing between anemia of chronic disease and iron deficiency 2

Common Pitfalls to Avoid

• Relying solely on hemoglobin and hematocrit for diagnosis, as they are late indicators of iron deficiency 1
• Failing to consider inflammation when interpreting ferritin levels - ferritin may be elevated above 12-15 μg/dl in patients with concurrent chronic inflammation, malignancy, or hepatic disease 2, 1
• Not recognizing that iron deficiency anemia in men and postmenopausal women often indicates gastrointestinal bleeding that requires further investigation 2, 1
• Assuming microcytosis is always due to iron deficiency when it could be caused by thalassemia or other hemoglobinopathies 2

Special Considerations

• CBC parameters can be useful discriminators for iron deficiency anemia when ferritin testing is not available, particularly in resource-limited settings 3
• Five CBC parameters have higher discriminating powers for iron deficiency anemia: RBC count, MCV, MCHC, MCH, and hematocrit 3
• In patients with chronic kidney disease, interpretation of ferritin levels is difficult due to its role as an acute-phase reactant 1