How to manage a patient with normocytic anemia, elevated ferritin, and normal folate and B12 levels?

Management of Normocytic Anemia with Elevated Ferritin

This patient has borderline low B12 (134 pg/mL, which is below the deficiency threshold of <150 pmol/L or <203 pg/mL) and should receive B12 replacement therapy before any other intervention, despite the normocytic picture. 1

Critical Laboratory Interpretation

Your patient's labs reveal:

• Mild normocytic anemia (Hgb 13.73 g/dL is borderline low for males, normal MCV 95.1 fL) 1
• B12 deficiency (134 pg/mL is below the 150 pmol/L threshold) 1
• Adequate iron stores (ferritin 179 ng/mL, iron 53 μg/dL, TIBC 210 μg/dL give transferrin saturation of 25%) 2
• Adequate folate (6.8 ng/mL is above the 4.4 μg/L deficiency threshold) 1

The key insight: B12 and folate deficiency can present with normocytic anemia in 9.2% of cases, not just macrocytic anemia. 3 This is a common clinical pitfall where providers miss vitamin deficiencies because they expect to see elevated MCV.

Immediate Diagnostic Steps

Order these tests now:

• Methylmalonic acid (MMA) - if >271 nmol/L, this confirms B12 deficiency even with borderline serum levels 1
• Reticulocyte count - to differentiate production failure from hemolysis/hemorrhage 1, 4
• Peripheral blood smear - look for hypersegmented neutrophils (suggests megaloblastic process), dysplastic features, or other abnormalities 4
• TSH and free T4 - hypothyroidism causes normocytic anemia and can coexist with B12 deficiency 1
• CRP - your ferritin of 179 ng/mL could represent inflammation masking concurrent iron deficiency 1

Red flag to watch: If the reticulocyte count is low/normal with this clinical picture, you're dealing with a production problem (B12 deficiency, hypothyroidism, or bone marrow issue). If elevated, consider hemolysis or recent bleeding. 1

Treatment Algorithm

Step 1: Treat B12 deficiency first

• Administer vitamin B12 1 mg intramuscularly three times weekly for 2 weeks, then 1 mg every 2-3 months for life 1
• Critical: Never start folate before B12 replacement - this can precipitate subacute combined degeneration of the spinal cord, a devastating neurological complication 1
• If neurological symptoms are present (paresthesias, ataxia, cognitive changes), use hydroxocobalamin 1 mg IM on alternate days until no further improvement 1

Step 2: Monitor response

• Recheck CBC in 4 weeks - expect hemoglobin increase of at least 2 g/dL if B12 deficiency was the primary cause 1
• If hemoglobin doesn't improve adequately, proceed to Step 3

Step 3: Evaluate for occult causes

Given the elevated ferritin (179 ng/mL) with borderline anemia:

• Check transferrin saturation - your calculated value of 25% (iron 53/TIBC 210) is borderline low, suggesting possible functional iron deficiency despite elevated ferritin 2, 1
• Evaluate for chronic disease/inflammation - ferritin acts as an acute phase reactant and can be falsely elevated up to 100 μg/L in inflammatory states while true iron deficiency exists 2, 1
• Consider gastrointestinal evaluation if anemia persists - occult GI blood loss is the most common cause of anemia in adult males, even with normal iron studies initially 2

Special Considerations for This Case

The elevated ferritin paradox: Your patient's ferritin of 179 ng/mL seems reassuring, but in the presence of inflammation (check CRP), this level doesn't exclude iron deficiency. Transferrin saturation <30% with ferritin <100 μg/L in inflammatory conditions suggests functional iron deficiency. 2, 1

Why normocytic with B12 deficiency? When B12 deficiency coexists with iron deficiency or chronic disease, the microcytic effect of iron deficiency can mask the macrocytic effect of B12 deficiency, resulting in a "normal" MCV. The red cell distribution width (RDW) would be elevated in this scenario. 1

Medication review: Ask specifically about methotrexate, hydroxyurea, azathioprine, or chronic NSAID use - these can cause normocytic anemia and affect vitamin metabolism. 1

When to Refer to Hematology

Refer immediately if: 1, 4

• Any other cytopenias develop (thrombocytopenia, leukopenia)
• Peripheral smear shows dysplastic features or blasts
• No response to B12 replacement after 4 weeks
• Unexplained persistent anemia after treating reversible causes

Bottom line: Start B12 replacement now based on the low serum level, confirm with MMA if needed, and reassess in 4 weeks. The normocytic picture doesn't exclude vitamin deficiency and shouldn't delay treatment. 1, 3