What is the best course of treatment for a patient with normocytic anemia, low iron, low iron saturation, elevated ferritin, and significantly elevated vitamin B12?

Treatment Approach for Normocytic Anemia with Functional Iron Deficiency and Elevated B12

This patient requires intravenous iron supplementation as first-line therapy, as the combination of low transferrin saturation (20.59%) with elevated ferritin (181 ng/mL) indicates functional iron deficiency (anemia of inflammation), which responds poorly to oral iron. 1

Understanding the Laboratory Pattern

Your patient presents with a classic pattern of functional iron deficiency (also called iron-restricted erythropoiesis):

• Transferrin saturation <20% indicates insufficient iron available for red blood cell production 1, 2
• Elevated ferritin (181 ng/mL) with low iron saturation suggests iron sequestration due to inflammation, where hepcidin upregulation prevents iron release from stores 1
• Normocytic anemia (MCV 91.5) with hemoglobin 8.6 g/dL represents moderate anemia requiring intervention 1
• Markedly elevated B12 (1737 pg/mL) is likely a red herring and does not require treatment in this context 3

Primary Treatment: Intravenous Iron

Intravenous iron is superior to oral iron when ferritin >100 ng/mL with low transferrin saturation, as inflammation-mediated hepcidin upregulation blocks intestinal iron absorption 1:

• Iron sucrose 200 mg IV infusions or ferric carboxymaltose are preferred formulations 1
• Studies in similar patients show hemoglobin increases of 1-3 g/dL within 6-10 weeks of IV iron therapy 1
• No test dose required for iron sucrose or ferric carboxymaltose 1

Why Not Oral Iron?

• Only 21% of patients with functional iron deficiency respond to oral iron after 4 weeks, compared to 65% with IV iron 1
• Oral iron further increases hepcidin levels, paradoxically worsening iron absorption 1
• The elevated ferritin indicates iron is present but sequestered, not absent 1

The Elevated B12: Clinical Significance

Do not treat the elevated B12 level—it is not causing the anemia and supplementation is contraindicated:

• Elevated B12 can occur with inflammation and does not indicate toxicity 3
• Importantly, B12 deficiency can mask iron deficiency by reducing erythropoiesis and falsely elevating iron parameters 3, 4
• However, your patient has the opposite scenario: very high B12 with clear functional iron deficiency 3
• The research showing B12 deficiency masking iron deficiency actually supports that once B12 is replete (as in your patient), the iron deficiency becomes apparent and requires treatment 3, 4

Monitoring Strategy

Recheck hemoglobin at 2-4 weeks, then complete iron panel at 8-10 weeks after IV iron 2:

• Do not recheck ferritin immediately after IV iron—it will be falsely elevated 2
• Target transferrin saturation >20% and ferritin 100-300 ng/mL 1
• If hemoglobin remains <10 g/dL after 8 weeks despite adequate iron repletion, consider erythropoietin-stimulating agents 1

Essential Workup Before Treatment

Rule out underlying causes of inflammation and blood loss:

• Evaluate for chronic kidney disease (check creatinine/GFR) as this commonly causes functional iron deficiency 1
• Screen for gastrointestinal pathology including malignancy if any GI symptoms present 1
• Check inflammatory markers (CRP) to confirm inflammatory state 1
• Thyroid function testing should be performed as hypothyroidism can contribute to anemia 1

Common Pitfalls to Avoid

• Do not prescribe oral iron first when ferritin is elevated—this wastes time and the patient will likely not respond 1
• Do not supplement B12 despite the low reticulocyte count (1.97%)—the elevated B12 level indicates adequate stores 3
• Do not wait for ferritin to drop below 100 before treating—functional iron deficiency requires treatment even with ferritin 100-300 ng/mL when transferrin saturation is low 1
• Avoid checking ferritin within 8 weeks of IV iron as it will remain artificially elevated 2