What is the next step in managing a patient with microcytic anemia and normal kidney function?

Next Step: Check Serum Ferritin

The next step is to measure serum ferritin, as it is the most powerful and specific test for diagnosing iron deficiency anemia in a patient with microcytic anemia (MCV 74) and normal kidney function. 1, 2

Diagnostic Algorithm

Initial Laboratory Interpretation

Your patient presents with:

• Elevated RBC count (6.26) with microcytosis (MCV 74) and low MCH (24.4)
• This pattern suggests either iron deficiency anemia or thalassemia trait 1
• The elevated red cell count with microcytosis specifically points toward thalassemia trait rather than iron deficiency, though iron deficiency must still be ruled out first 1

Step 1: Serum Ferritin (Most Critical Test)

• Ferritin <12 μg/dL is diagnostic of iron deficiency 1
• Ferritin 12-100 μg/dL may still indicate iron deficiency if inflammation, malignancy, or liver disease is present (ferritin is an acute phase reactant) 1
• Ferritin >100 μg/dL essentially excludes iron deficiency 1
• A practical cut-off of 45 μg/L provides optimal sensitivity and specificity 3

Step 2: Additional Testing Based on Ferritin Results

If ferritin confirms iron deficiency (<12-45 μg/dL):

• Check transferrin saturation (<30% supports iron deficiency) 1
• Measure RDW: elevated RDW (>14.0%) with low MCV indicates iron deficiency, while RDW ≤14.0% with low MCV suggests thalassemia minor 2, 3
• Start oral iron therapy (ferrous sulfate 200 mg three times daily) and expect hemoglobin rise ≥10 g/L within 2 weeks to confirm diagnosis 1, 3
• Investigate the source of iron loss: evaluate for GI blood loss, malabsorption (including celiac disease screening), or inadequate dietary intake 3

If ferritin is normal or elevated (>45-100 μg/dL):

• Consider thalassemia (especially given the elevated RBC count with severe microcytosis) 1, 2
• Order hemoglobin electrophoresis to identify hemoglobinopathies 2
• Consider anemia of chronic disease if inflammatory markers are elevated 2
• Rule out sideroblastic anemia if ferritin and transferrin saturation are both elevated 2

Step 3: If Diagnosis Remains Unclear

Two definitive approaches when doubt persists:

• Therapeutic trial of oral iron for 3 weeks: hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency 1, 3
• Bone marrow aspiration: identifies ring sideroblasts (pathognomonic for sideroblastic anemia) or genetic disorders of iron metabolism 1, 2

Common Pitfalls to Avoid

• Do not assume ethnicity explains microcytosis—always confirm hemoglobinopathies with laboratory testing, not ethnic background alone 1
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency 3
• Do not miss genetic disorders: if ferritin is low-normal with low transferrin saturation, or if there's family history of refractory anemia, consider genetic disorders like IRIDA 2, 3
• Do not ignore inflammation: ferritin can be falsely elevated in infection, malignancy, or liver disease, potentially masking concurrent iron deficiency 1

Treatment Considerations Once Diagnosed

For confirmed iron deficiency:

• First-line: ferrous sulfate 200 mg three times daily for at least 3 months after anemia correction to replenish stores 3, 4
• Alternative formulations (ferrous gluconate, ferrous fumarate) if not tolerated; add ascorbic acid to enhance absorption 3
• Monitor hemoglobin at 2 weeks (expect ≥10 g/L rise), then at 3-month intervals for one year 3
• IV iron if malabsorption present, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 3

For thalassemia or genetic disorders:

• Avoid unnecessary iron therapy 3
• Consider genetic counseling and specific management based on type 2