What is the cause of microcytic anemia in a patient with normal ferritin levels, elevated vitamin B12 levels, and normal folate levels, and how should it be managed?

Interpretation: This is NOT Iron Deficiency Anemia

Your patient's labs show normal iron stores (ferritin 211 μg/L) with adequate transferrin saturation (27%), which essentially rules out iron deficiency as the cause of microcytic anemia. 1, 2

Key Laboratory Interpretation

• Ferritin >100 μg/L makes iron deficiency almost certainly not present - your patient's ferritin of 211 μg/L is well above this threshold 2
• Transferrin saturation of 27% is above the <20% cutoff for iron deficiency (normal is typically >20%) 3, 1
• The combination of microcytosis with normal-to-elevated ferritin and adequate transferrin saturation points away from iron deficiency 4, 5

Differential Diagnosis to Pursue

You must now investigate alternative causes of microcytic anemia:

1. Thalassemia Trait (Most Likely)

• Order hemoglobin electrophoresis immediately - this is essential when microcytosis exists with normal iron studies 1, 6
• Look for elevated hemoglobin A2 levels (>3.5%), which confirms beta-thalassemia trait 4
• Check if RDW is normal or near-normal (≤14.0%), which favors thalassemia over iron deficiency 1, 6
• Elevated red blood cell count with microcytosis strongly suggests thalassemia trait rather than iron deficiency 2

2. Anemia of Chronic Disease/Inflammation

• Although less likely with your patient's transferrin saturation of 27%, check inflammatory markers (CRP, ESR) 3
• Anemia of chronic disease typically shows transferrin saturation <16-20% with ferritin >100 μg/L 3
• Your patient's TSAT of 27% makes this diagnosis less probable 3

3. Sideroblastic Anemia (Consider if Above Negative)

• If hemoglobin electrophoresis is normal and no inflammatory disease is found, consider bone marrow examination to look for ring sideroblasts 2
• Sideroblastic anemia shows elevated ferritin and transferrin saturation even before transfusions, with pathognomonic ring sideroblasts on bone marrow 2

4. Genetic Disorders of Iron Metabolism (Rare)

• Consider genetic testing for disorders like SLC11A2, STEAP3, SLC25A38, or ALAS2 defects if extreme microcytosis (MCV <70 fL) or positive family history 1, 6
• These conditions may present with paradoxically normal or elevated ferritin despite functional iron deficiency 1

Critical Management Points

DO NOT give iron supplementation - with ferritin of 211 μg/L, iron therapy is not indicated and could lead to iron overload 1, 2

Next immediate steps:

1. Order hemoglobin electrophoresis 1, 6
2. Review complete blood count for RDW and red cell count 1, 6
3. Check inflammatory markers (CRP, ESR) if not already done 3
4. Obtain detailed family history of anemia or ethnic background suggesting hemoglobinopathy 1

Common Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency - up to 20-30% of microcytic anemia cases have alternative diagnoses 7
• Do not presume thalassemia based on ethnicity alone - laboratory confirmation with hemoglobin electrophoresis is mandatory 2
• Do not overlook combined deficiencies - although B12 (760) and folate (9.3) are normal here, always verify these don't coexist with other causes 1, 6
• Ferritin is an acute phase reactant - while 211 μg/L is high enough to exclude iron deficiency even with inflammation, be aware this can mask concurrent iron deficiency in borderline cases (30-100 μg/L range) 3, 2