How to manage elevated ferritin with low iron levels in a patient?

Management of Elevated Ferritin with Low Iron in a 74-Year-Old Patient

This patient has functional iron deficiency in the setting of inflammation, and should be investigated for the underlying inflammatory cause before considering iron supplementation. 1

Clinical Interpretation of Laboratory Findings

Your patient presents with a classic pattern of anemia of chronic disease (ACD) with possible functional iron deficiency:

• Low serum iron (10 μmol/L) with elevated ferritin (533 μg/L) indicates iron sequestration in storage sites rather than true iron depletion 1
• Transferrin saturation of 19% falls just below the 20% threshold, suggesting inadequate iron availability for erythropoiesis despite adequate stores 1
• Mild anemia (Hgb 112 g/L) with normal MCV indicates this is not classic iron deficiency anemia 1
• The laboratory comment correctly identifies inflammation, tissue damage, renal impairment, or hyperthyroidism as potential causes 1

Distinguishing Functional Iron Deficiency from Inflammatory Block

The critical distinction is whether this represents functional iron deficiency (treatable with iron) versus pure inflammatory iron block (not treatable with iron until inflammation resolves). 1

Key Differentiating Features:

• Functional iron deficiency: Serial ferritin levels decrease during therapy but remain elevated (>100 ng/mL); responds to IV iron 1
• Inflammatory iron block: Abrupt increase in ferritin with sudden drop in transferrin saturation; does not respond to iron until inflammation resolves 1

In your patient with ferritin 533 μg/L and transferrin saturation 19%, both conditions remain possible. 1

Recommended Diagnostic Workup

Before considering iron therapy, investigate for underlying inflammatory or pathologic conditions:

• Inflammatory markers: CRP, ESR to quantify inflammation 1
• Renal function: Creatinine, eGFR (given age and anemia pattern) 1
• Liver function tests: AST, ALT, GGT (ferritin is elevated in liver disease) 1, 2
• Thyroid function: TSH (hyperthyroidism mentioned in lab comment) 1
• Malignancy screening: Age-appropriate cancer screening, as malignancy is the most common cause of markedly elevated ferritin 2
• Chronic inflammatory conditions: Consider rheumatologic diseases, chronic infections 1, 2

Management Algorithm

If Inflammation is Identified:

Treat the underlying inflammatory condition first. 1 Iron supplementation will be ineffective until inflammation is controlled, and ferritin is an acute-phase reactant that will remain elevated regardless of iron therapy. 1

If No Clear Inflammatory Cause or Persistent Anemia Despite Treatment:

Consider a therapeutic trial of IV iron if the patient has symptomatic anemia or requires erythropoiesis-stimulating agents (ESAs). 1

The DRIVE study provides the strongest evidence for this approach: 1

• Patients with ferritin 500-1200 ng/mL and transferrin saturation <25% received IV ferric gluconate 125 mg over 8 consecutive sessions
• Hemoglobin increased significantly more in the IV iron group (16±13 vs 11±14 g/L, P=0.028) 1
• Baseline ferritin was not predictive of iron responsiveness 1

Specific protocol if proceeding with therapeutic trial: 1

• Administer weekly IV iron 50-125 mg for 8-10 doses
• Monitor hemoglobin response
• If no erythropoietic response occurs, inflammatory block is most likely and discontinue iron until inflammation resolves 1

Safety Considerations:

Withhold iron therapy if: 1

• Ferritin exceeds 1000 ng/mL 1
• Transferrin saturation exceeds 50% 1

The safety of administering IV iron with ferritin >500 ng/mL remains uncertain, as studies were not powered to assess safety outcomes including infections, cardiovascular events, and death. 1 Balance the probability of hemoglobin improvement against perceived individual risk. 1

Common Pitfalls to Avoid

• Do not assume elevated ferritin always means iron overload - ferritin is an acute-phase reactant and rises with inflammation, malignancy, liver disease, and tissue damage 1, 2
• Do not give oral iron - it is unlikely to overcome functional iron deficiency in the setting of inflammation; IV iron is required if supplementation is indicated 3
• Do not ignore the underlying cause - treating iron parameters without addressing inflammation will be ineffective and potentially harmful 1
• Do not use ferritin alone to guide therapy - always interpret ferritin together with transferrin saturation, hemoglobin level, inflammatory markers, and clinical context 1