What is the treatment for hyperferritinemia (elevated ferritin levels)?

Treatment for High Ferritin (Hyperferritinemia)

Therapeutic phlebotomy is the mainstay of treatment for hyperferritinemia due to iron overload, with the goal of reducing serum ferritin to 50-100 μg/L through weekly removal of 400-500 mL of blood, followed by maintenance therapy. 1, 2

Diagnostic Approach Before Treatment

• Determine if hyperferritinemia is due to iron overload by measuring transferrin saturation (TS) alongside ferritin 2
• If TS ≥45% and ferritin is elevated, genetic testing for hereditary hemochromatosis (HFE) should be considered 1, 2
• 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 Phase (Induction)

• Initiate weekly therapeutic phlebotomy (removal of 400-500 mL of blood) when:
  • Men have serum ferritin levels ≥300 μg/L 2
  • Women have serum ferritin levels ≥200 μg/L 2
• Monitor hemoglobin and hematocrit before each phlebotomy session 1
• If hemoglobin <12 g/dL, decrease frequency of phlebotomy 1
• If hemoglobin <11 g/dL, discontinue phlebotomy and reassess later 1
• Check serum ferritin monthly or after every 4th phlebotomy 1
• When ferritin decreases below 200 μg/L, monitor every 1-2 sessions 1

Target Levels

• Continue therapeutic phlebotomy until ferritin reaches target of 50 μg/L 1
• During maintenance phase, maintain serum ferritin between 50-100 μg/L 2

Maintenance Therapy

• After achieving target ferritin, continue maintenance phlebotomies every 1-4 months 1
• Monitor serum ferritin every 6 months to adjust treatment schedule 1
• On average, serum ferritin rises by approximately 100 μg/L per year without treatment 1

Dietary and Lifestyle Modifications

• Avoid iron supplements and iron-fortified foods 1, 2
• Limit vitamin C supplements, which enhance iron absorption 1, 2
• Limit red meat consumption 1
• Restrict alcohol intake, especially during iron depletion phase 1
• Patients with cirrhosis should abstain from alcohol completely 1
• Consume fruit juices and citrus fruits in moderation, not with meals 1
• Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection 1, 3

Special Considerations

Alternative Treatment Options

• For patients with severe iron overload (>30g total iron stores), therapeutic erythrocytapheresis may be considered as it can remove up to 1000mL of erythrocytes per session, potentially reducing treatment duration by 70% 4
• Iron chelation therapy with deferasirox may be considered for patients who cannot tolerate phlebotomy 5
  • Deferasirox should only be used when serum ferritin is consistently >1000 μg/L 5
  • Monitor for potential side effects including renal dysfunction, hepatotoxicity, and bone marrow suppression 5

Monitoring During Treatment

• Monitor serum ferritin monthly during initial therapy and every 3-6 months during maintenance 2
• Regularly check plasma folate and cobalamin, especially in patients requiring numerous phlebotomies 1
• Unexpected changes in serum ferritin or transferrin saturation should always be investigated 1

Pitfalls and Caveats

• Not all cases of hyperferritinemia represent true iron overload—elevated ferritin can be seen in inflammatory conditions, liver disease, and malignancies 6
• Avoid overchelation by careful monitoring of ferritin levels 2
• Early treatment before development of cirrhosis and diabetes improves survival to normal population levels 2
• In patients with non-HFE hyperferritinemia, treatment decisions should be based on evidence of actual iron overload rather than ferritin levels alone 6
• Dietary modifications should not substitute for iron removal therapy in cases of true iron overload 1