What is the appropriate management for a patient with macrocytic anemia, elevated ferritin, and low iron levels?

Anemia of Chronic Inflammation with Functional Iron Deficiency

This patient has anemia of chronic inflammation (also called anemia of chronic disease) with functional iron deficiency, characterized by low-normal serum iron (89 μg/dL), markedly elevated ferritin (787 ng/mL), and macrocytic anemia (MCV 96.8 fL). The elevated ferritin with relatively low serum iron indicates iron sequestration due to inflammatory processes, not true iron deficiency. 1

Diagnostic Interpretation

The laboratory pattern is pathognomonic for anemia of inflammation:

• Ferritin >300 ng/mL with low-normal iron strongly suggests inflammatory anemia, not iron deficiency anemia. 1 When ferritin exceeds 300 ng/mL, iron sequestration in the reticuloendothelial system (mediated by hepcidin upregulation) is the primary mechanism. 1
• The macrocytic component (MCV 96.8 fL) requires additional evaluation for B12/folate deficiency, though this can coexist with inflammatory anemia. 2
• The markedly elevated RDW (46.6 fL) indicates significant red cell size heterogeneity, consistent with mixed pathology or chronic disease. 3

Essential Next Steps

Obtain transferrin saturation (TSAT) immediately to confirm functional iron deficiency:

• TSAT <20% with ferritin >300 ng/mL definitively establishes anemia of inflammation. 1
• If TSAT is available and <20%, this confirms iron is sequestered but not truly deficient. 1

Check vitamin B12, folate, and thyroid function to address the macrocytic component:

• The macrocytosis may represent a separate deficiency that requires correction. 1, 3
• Thyroid dysfunction commonly coexists with anemia in elderly patients. 1

Evaluate for underlying inflammatory conditions:

• Check C-reactive protein (CRP) to quantify inflammation. 1
• Assess renal function (creatinine, GFR) as chronic kidney disease commonly causes this pattern. 1
• Consider cardiac evaluation if heart failure is suspected, as this is a common cause of this anemia pattern in elderly patients. 1

Management Algorithm

Do NOT give oral iron supplementation—it will be ineffective and potentially harmful:

• Oral iron cannot overcome hepcidin-mediated blockade of intestinal absorption in inflammatory states. 1
• Ferritin is already elevated at 787 ng/mL; adding more iron risks toxicity without benefit. 1

If transferrin saturation is <20% AND the patient is symptomatic (hemoglobin 10.0 g/dL):

• Consider intravenous iron (iron sucrose or ferric carboxymaltose) as it bypasses intestinal hepcidin blockade. 1 Multiple randomized controlled trials (FAIR-HF, CONFIRM-HF) demonstrated that IV iron improves hemoglobin, functional status, and quality of life even with ferritin >300 ng/mL when TSAT is low. 1
• Monitor ferritin and keep it below 500 ng/mL to avoid iron overload toxicity. 1, 3

Treat the underlying inflammatory condition:

• The anemia will not fully resolve without addressing the root cause of inflammation. 1
• If heart failure is present, optimizing cardiac management improves anemia outcomes. 1
• If chronic kidney disease (CKD) is present, consider erythropoietin-stimulating agents in addition to IV iron. 1

Critical Pitfalls to Avoid

Do not misinterpret elevated ferritin as iron overload:

• Ferritin acts as an acute phase reactant in inflammation, generating falsely elevated values. 1, 3
• The key is the transferrin saturation—if low, iron is sequestered but functionally unavailable. 1, 3

Do not prescribe oral iron based on "low iron" alone:

• The serum iron of 89 μg/dL is low-normal, not truly deficient. 1
• Oral iron will not be absorbed due to hepcidin upregulation and may cause gastrointestinal side effects without benefit. 1

Do not overlook combined deficiencies:

• The macrocytosis suggests possible B12 or folate deficiency that requires separate treatment. 3, 2
• Treating only one component will leave the patient partially corrected. 3

Do not delay investigation of the underlying cause:

• In elderly patients with new anemia of inflammation, malignancy, occult infection, and autoimmune disease must be excluded. 4, 5