Laboratory Tests to Reassess Iron Deficiency Anemia
Order a complete blood count with red cell indices (MCV, MCH, RDW), reticulocyte count, serum ferritin, transferrin saturation, and CRP to reassess iron deficiency anemia. 1, 2
Minimum Essential Laboratory Panel
The core reassessment workup should include:
- Complete blood count (CBC) with hemoglobin, hematocrit, and differential white blood cell count 1, 2
- Red cell indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW) 1, 2
- Reticulocyte count to assess bone marrow response and distinguish production defects from hemolysis or ongoing blood loss 1, 2
- Serum ferritin as the most powerful single test for iron deficiency 1, 2
- Transferrin saturation (TfS) to evaluate iron available for erythropoiesis 1, 2
- C-reactive protein (CRP) to assess for inflammation that confounds ferritin interpretation 1, 2
Interpreting Iron Studies Based on Inflammatory Status
The diagnostic thresholds for iron deficiency depend critically on whether inflammation is present:
- Without inflammation: Serum ferritin <30 μg/L confirms iron deficiency 1
- With inflammation: Serum ferritin up to 100 μg/L may still indicate iron deficiency because ferritin is an acute-phase reactant 1
- Transferrin saturation <20% indicates functional or absolute iron deficiency regardless of inflammatory status 1, 2
- Ferritin >100 μg/L with transferrin saturation <20% suggests anemia of chronic disease 1
- Ferritin 30-100 μg/L in the presence of inflammation likely represents mixed iron deficiency and anemia of chronic disease 1
Extended Workup When Initial Tests Are Inconclusive
If the cause of anemia remains unclear after the minimum workup, add:
- Vitamin B12 and folate levels to exclude nutritional deficiencies, particularly if MCV is elevated or normal despite suspected iron deficiency 1
- Haptoglobin and lactate dehydrogenase to evaluate for hemolysis if reticulocyte count is elevated 1
- Percentage of hypochromic red cells and reticulocyte hemoglobin content for more sensitive detection of functional iron deficiency, though these require specialized equipment 1, 2
- Soluble transferrin receptor (sTfR) to distinguish iron deficiency from anemia of chronic disease, particularly in inflammatory conditions 1, 2
- Creatinine and urea to assess for renal contribution to anemia 1
Key Interpretation Principles
Understanding how to interpret these tests together is essential:
- RDW >14% suggests iron deficiency even when MCV appears normal due to coexisting macrocytosis and microcytosis neutralizing each other 1, 2
- MCH is more reliable than MCV for detecting iron deficiency as it is less dependent on storage conditions and counting equipment 1, 2
- Low or "normal" reticulocyte count with anemia indicates inappropriate bone marrow response, suggesting deficiency states or primary bone marrow disease 1
- Elevated reticulocyte count excludes deficiencies and points toward hemolysis or acute blood loss 1
- Microcytosis with normal iron studies warrants hemoglobin electrophoresis to exclude thalassemia, particularly in appropriate ethnic backgrounds 1
Common Pitfalls to Avoid
- Do not rely on hemoglobin and hematocrit alone as they are late indicators of iron deficiency and will miss early depletion 1, 2, 3
- Do not interpret ferritin without measuring CRP as inflammation falsely elevates ferritin, leading to missed diagnoses in patients with chronic disease 1, 2, 4
- Do not assume normal MCV excludes iron deficiency as combined deficiencies (iron plus B12/folate) can produce a normal MCV with elevated RDW 1, 2
- Do not fail to measure transferrin saturation as it is less affected by inflammation than ferritin and may be the only abnormal test in functional iron deficiency 1, 2
- Do not order bone marrow examination before completing the extended biochemical workup and consulting hematology 1