What labs are necessary to investigate iron deficiency anemia?

Laboratory Tests for Investigating Iron Deficiency Anemia

Serum ferritin is the most powerful test for diagnosing iron deficiency anemia and should be included in the initial laboratory evaluation along with complete blood count and transferrin saturation. 1, 2, 3

Initial Laboratory Evaluation

• Complete Blood Count (CBC) is the recommended first step in evaluating for iron deficiency anemia, providing information on hemoglobin levels and red cell indices 2, 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 1, 3
• Red cell indices (MCV, MCH, MCHC) provide sensitive indication of iron deficiency in the absence of chronic disease or hemoglobinopathy 1, 2
• Elevated red cell distribution width (RDW >14.0%) with microcytosis strongly suggests iron deficiency anemia 3

Essential Iron Studies

• Serum ferritin is the most sensitive test for iron stores; levels <25 ng/ml in males and <11 ng/ml in females indicate insufficient iron stores 1, 3
• Transferrin saturation represents iron available to bone marrow for erythropoiesis and is less affected by inflammation than ferritin 1, 2
• Reticulocyte count helps evaluate the appropriateness of bone marrow response to anemia 1

Additional Useful Tests

• Percent hypochromic red blood cells (PHRBC) and content of hemoglobin in reticulocytes (CHr) can identify functional iron deficiency but require specialized equipment 1, 4
• Reticulocyte hemoglobin content (CHr) is an early marker of iron-deficient erythropoiesis and can predict response to iron therapy 4

Diagnostic Algorithm

1. Measure hemoglobin to confirm anemia 1, 3
2. Assess red cell indices (MCV, MCH, MCHC, RDW) to characterize the anemia 1, 3
3. Measure serum ferritin as the primary marker of iron stores 1, 2
4. Add transferrin saturation to improve diagnostic accuracy 1, 3
5. Screen all patients for celiac disease, particularly premenopausal women 1, 2

Special Considerations

• In inflammatory states, ferritin may be falsely elevated as an acute phase reactant; use a higher ferritin threshold (<100 μg/L) to diagnose iron deficiency when inflammation is present 2, 3
• In patients with chronic kidney disease, interpretation of ferritin levels is difficult due to its role as an acute-phase reactant 1
• Consider measuring C-reactive protein to assess the contribution of inflammation to elevated serum ferritin levels 1

Common Pitfalls to Avoid

• Relying solely on hemoglobin and hematocrit for diagnosis, as they are late indicators of iron deficiency 3, 5
• Failing to consider inflammation when interpreting ferritin levels 2, 3
• Not recognizing that iron deficiency anemia in men and postmenopausal women often indicates gastrointestinal bleeding that requires further investigation 1, 6
• Ordering CBC alone without examining the indicators of iron status may lead to missed diagnoses, as individuals with normal CBC parameters can still have reduced serum iron and ferritin levels 5