What is the management of elevated ferritin levels?

Management of Elevated Ferritin Levels

The management of elevated ferritin requires a systematic diagnostic approach to determine the underlying cause, as iron overload is not the most common etiology of hyperferritinemia in the general population. 1

Initial Evaluation

• Always measure both serum ferritin and transferrin saturation (TS) together rather than relying on a single test to properly evaluate iron status 1
• Consider the following common causes of elevated ferritin:
  • Inflammatory conditions (alcoholic liver disease, viral hepatitis, NAFLD) 1
  • Malignancy (especially hematologic) 2
  • Chronic inflammatory conditions (rheumatologic diseases) 1
  • Iron overload disorders (hereditary hemochromatosis) 1
  • Metabolic syndrome, obesity, and diabetes 3

Diagnostic Algorithm

1. Step 1: Assess both transferrin saturation and ferritin levels

   • If TS ≥ 45% and/or elevated ferritin: Proceed to HFE genotype testing 1
   • If TS < 45% and normal ferritin: No further evaluation needed 1

2. Step 2: Evaluate for non-iron overload causes if TS < 45%

   • Check inflammatory markers (CRP, ESR) 1
   • Assess liver enzymes (ALT, AST) 1
   • Screen for metabolic syndrome, alcohol use 3
   • Consider malignancy workup if clinically indicated 2

3. Step 3: For patients with elevated TS ≥ 45%

   • Perform HFE gene mutation analysis (C282Y, H63D) 1
   • Results interpretation:
     • C282Y/C282Y homozygotes: Hereditary hemochromatosis 1
     • C282Y/H63D compound heterozygotes: Possible iron overload 1
     • Other genotypes: Consider non-HFE iron overload or secondary causes 1

Management Based on Ferritin Level and Cause

For Hereditary Hemochromatosis:

• Ferritin < 1000 μg/L: Therapeutic phlebotomy to achieve ferritin < 50 μg/L 1
• Ferritin > 1000 μg/L:
  • Evaluate for liver disease (increased risk of cirrhosis) 1
  • Consider liver biopsy if ferritin > 1000 μg/L with elevated liver enzymes and platelets < 200,000/μL (80% risk of cirrhosis) 1
  • Initiate therapeutic phlebotomy 1

For Secondary Causes:

• Inflammatory conditions: Treat the underlying condition rather than the elevated ferritin 1
• Metabolic syndrome/NAFLD: Weight loss, lifestyle modifications 3
• Alcohol-related: Alcohol cessation 3

For Chronic Kidney Disease:

• In hemodialysis patients with elevated ferritin (500-1200 μg/L) but low transferrin saturation (<25%), intravenous iron may still be beneficial for anemia management 1
• Monitor for adverse events when administering IV iron with elevated ferritin 1

Special Considerations

• Extremely high ferritin (>10,000 μg/L): Consider adult-onset Still's disease, hemophagocytic lymphohistiocytosis, or malignancy 2

• Referral criteria: Consider specialist referral if:

  • Ferritin > 1000 μg/L 3
  • Cause remains unclear after initial workup 3
  • Evidence of organ damage 1

• Iron chelation therapy: For transfusional iron overload with ferritin consistently > 1000 μg/L, consider deferasirox therapy 4

  • Monitor renal function, liver enzymes, and auditory/visual function 4
  • Interrupt therapy if ferritin falls below 500 μg/L 4
  • Adjust dose based on ferritin trends to avoid overchelation 4

Monitoring

• For patients with iron overload: Monitor serum ferritin monthly and adjust therapy every 3-6 months based on trends 4
• For patients with secondary causes: Monitor based on the underlying condition 1
• For patients on iron chelation: Monitor complete blood count, liver function, renal function, and ferritin monthly 4

Common Pitfalls to Avoid

• Assuming elevated ferritin always indicates iron overload; in fact, inflammatory conditions are more common causes 1, 2
• Initiating phlebotomy without confirming iron overload diagnosis 3
• Failing to consider multiple causes, as 41% of patients with hyperferritinemia have more than one underlying condition 5
• Overlooking the need for liver biopsy in patients with ferritin > 1000 μg/L and abnormal liver tests 1
• Using ferritin alone without transferrin saturation to diagnose iron overload 1