What is the management for elevated ferritin levels?

Management of Elevated Ferritin Levels

The management of elevated ferritin levels should focus on identifying the underlying cause, with referral to a specialist recommended for ferritin levels >1000 μg/L or when the cause remains unclear despite initial workup. 1, 2

Diagnostic Approach

Initial Evaluation

• Serum ferritin and transferrin saturation are the first diagnostic steps to identify the cause of hyperferritinaemia 1, 3
• Thresholds for iron overload suspicion:
  • Men: >300 μg/L
  • Women: >200 μg/L 1

Secondary Causes to Rule Out

• Alcohol consumption
• Metabolic syndrome/obesity
• Diabetes
• Liver disease (especially non-alcoholic fatty liver disease)
• Malignancy
• Infection or inflammation
• Anemia of chronic disease 2, 4

Advanced Testing

• For ferritin >1000 μg/L: Consider specialist referral (hematology or gastroenterology) 1, 2
• Liver iron concentration assessment:
  • MRI is the preferred non-invasive method for diagnosing and monitoring hepatic iron overload 3
  • Liver biopsy should be reserved for selected patients with hereditary hemochromatosis or when other diagnoses are being considered 3

Management Based on Etiology

Hereditary Hemochromatosis

• Therapeutic phlebotomy is the mainstay of treatment 1
  • Induction phase: Weekly phlebotomy (400-500 mL, containing 200-250 mg iron) until ferritin reaches 50-100 μg/L
  • Maintenance phase: Individualized frequency based on reaccumulation rate

Iron Overload from Transfusions

• Iron chelation therapy (e.g., deferasirox) when phlebotomy is contraindicated 5
• Dosing considerations for deferasirox:
  • Starting dose: 14 mg/kg/day for patients with eGFR >60 mL/min/1.73m² 5
  • Monitor serum ferritin monthly and adjust dose every 3-6 months 5
  • Target ferritin level: 500-1000 μg/L 5
  • If ferritin falls below 500 μg/L, interrupt therapy 5

Non-Iron Overload Causes (90% of elevated ferritin cases) 2

• Treat the underlying condition:
  • Metabolic syndrome: Weight loss, diabetes management
  • Alcohol-related: Alcohol cessation
  • Inflammatory conditions: Appropriate anti-inflammatory therapy
  • Malignancy: Oncology referral and treatment

Monitoring

• Monitor ferritin and transferrin saturation every 3 months during initial treatment 1
• Once stabilized, check at least annually 1
• For patients on deferasirox:
  • Monitor blood counts, liver function, renal function monthly 5
  • Adjust dose based on serum ferritin trends 5

Important Clinical Considerations

Risk Stratification

• Ferritin >1000 μg/L is associated with increased risk of cirrhosis in hemochromatosis 6
• In NAFLD, elevated ferritin (>1.5× upper limit of normal) is independently associated with advanced fibrosis and increased mortality 7, 8

Cautions with Treatment

• Avoid overchelation: If ferritin falls below 1000 μg/L, consider dose reduction of chelation therapy 5
• Special populations:
  • Elderly patients: Monitor more frequently for toxicity with deferasirox 5
  • Patients with renal impairment: Adjust deferasirox dosing or consider alternative therapy 5
  • Patients with hepatic impairment: Reduce starting dose by 50% in moderate impairment; avoid in severe impairment 5

Potential Complications

• Deferasirox can cause serious adverse effects including:
  • Renal toxicity
  • Hepatotoxicity
  • Gastrointestinal hemorrhage
  • Severe skin reactions
  • Auditory and ocular abnormalities 5

By following this structured approach to the evaluation and management of elevated ferritin, clinicians can effectively identify and treat the underlying cause, potentially preventing progression to end-organ damage in cases of true iron overload.