How to manage hyperferritinemia?

Management of High Ferritin (Hyperferritinemia)

Therapeutic phlebotomy is the cornerstone treatment for hyperferritinemia with iron overload, with the goal of reducing serum ferritin to 50-100 μg/L through regular blood removal. 1, 2

Diagnostic Approach

• Determine if hyperferritinemia is due to iron overload or other causes (inflammation, liver disease, malignancy) through transferrin saturation measurement 2
• Evaluate for hereditary hemochromatosis (HFE) through genetic testing if transferrin saturation is elevated 1
• Assess for end-organ damage through liver function tests and consider liver biopsy if cirrhosis is suspected 1, 2

Treatment Protocol for Iron Overload

• Initial Therapy (Iron Depletion Phase)

  • Initiate weekly therapeutic phlebotomy (removal of 400-500 mL of blood) as tolerated 2
  • Monitor hemoglobin and hematocrit before each phlebotomy session 1
  • Postpone phlebotomy if anemia develops until resolved 1
  • Check serum ferritin every 10-12 phlebotomies initially, more frequently as levels approach normal range 1
  • Continue until ferritin reaches target of less than 50 μg/L 1

• Maintenance Therapy

  • After achieving target ferritin, continue maintenance phlebotomies every 3-6 months 1
  • Maintain serum ferritin between 50-100 μg/L 1, 2
  • Alternative approach: cease phlebotomy and monitor ferritin, restarting when ferritin reaches upper limit of normal 1

Special Considerations

• Dietary Modifications

  • Avoid iron supplements and iron-fortified foods 1, 2
  • Limit vitamin C supplements to 500 mg/day as higher doses may increase iron absorption 1
  • Avoid excess alcohol consumption which can worsen liver damage 1
  • Maintain a broadly healthy diet rather than strict iron restriction 1

• For Patients Unable to Tolerate Phlebotomy

  • Consider iron chelation therapy with deferasirox in patients with anemia or poor venous access 3
  • Monitor for potential side effects of chelation therapy including:
    • Renal toxicity (monitor eGFR) 3
    • Hepatic toxicity (monitor liver enzymes) 3
    • Gastrointestinal ulceration 3
    • Bone marrow suppression 3

• Alternative Approaches

  • Erythrocytapheresis may be more efficient than standard phlebotomy in selected patients, removing twice as much iron per session 4, 5
  • Proton pump inhibitors may reduce iron absorption and decrease maintenance phlebotomy requirements 1

Monitoring

• Monitor serum ferritin monthly during initial therapy and every 3-6 months during maintenance 1, 2
• For patients with cirrhosis, perform regular screening for hepatocellular carcinoma 1
• In patients with secondary iron overload (e.g., from transfusions), tailor treatment approach to the underlying cause 1
• For patients with NAFLD and hyperferritinemia, phlebotomy may improve insulin resistance 6

Pitfalls and Caveats

• Hyperferritinemia is not always due to iron overload - only about 10% of cases relate to true iron overload 7
• Avoid overchelation by careful monitoring of ferritin levels 3
• Patients with cirrhosis and iron overload should avoid raw shellfish due to risk of Vibrio vulnificus infection 2
• Early treatment before development of cirrhosis and diabetes improves survival to normal population levels 1