What is the treatment for high ferritin levels due to iron overload?

Treatment of High Ferritin Due to Iron Overload

The primary treatment for high ferritin levels due to iron overload is therapeutic phlebotomy, which should be initiated when serum ferritin levels reach 1,000 ng/mL or when patients require 2 or more units of blood transfusion per month for over a year. 1, 2

Diagnostic Approach Before Treatment

• Determine if hyperferritinemia is due to true iron overload by measuring transferrin saturation - elevated transferrin saturation confirms iron overload 2
• Consider genetic testing for hereditary hemochromatosis (HFE) if transferrin saturation is elevated 2
• Assess for end-organ damage through liver function tests and consider liver biopsy if cirrhosis is suspected 2, 1

Treatment Protocol

Therapeutic Phlebotomy

• Initiate weekly therapeutic phlebotomy (removal of 400-500 mL of blood) as tolerated by the patient 1, 3, 2
• Check hemoglobin and hematocrit before each phlebotomy session; do not allow hematocrit to fall by more than 20% of prior level 1, 2
• Monitor serum ferritin levels every 10-12 phlebotomies initially, more frequently as levels approach normal range 1, 2
• Continue therapeutic phlebotomy until ferritin reaches target of 50-100 μg/L 1, 3, 2
• The number of phlebotomies required correlates strongly with initial serum ferritin levels rather than transfusion burden 4

Iron Chelation Therapy

• For patients who cannot tolerate phlebotomy or have anemia, iron chelation therapy with deferasirox is an alternative 1, 5
• Deferasirox dosing is typically 5-30 mg/kg/day based on liver iron concentration 5
• Monitor for side effects including headache, nausea, and dizziness 5, 4

Maintenance Therapy

• After reaching target ferritin levels (50-100 μg/L), continue maintenance phlebotomies every 3-6 months 3, 2, 6
• Monitor serum ferritin monthly during initial therapy and every 3-6 months during maintenance 2
• Adjust frequency of maintenance phlebotomies to keep ferritin between 50-100 μg/L 3, 2

Special Considerations

Patient-Specific Factors

• For patients with myelodysplastic syndromes (MDS), chelation therapy should be considered when ferritin exceeds 1,000 ng/mL and life expectancy is greater than one year 1
• Patients with cirrhosis and iron overload should avoid raw shellfish due to risk of Vibrio vulnificus infection 3, 2
• Patients with low-risk MDS, IPSS low or intermediate-1, WHO RA, RARS, and 5q- are most likely to benefit from iron overload management 1

Dietary and Supplement Recommendations

• Avoid iron supplements and iron-fortified foods 1, 2
• Limit vitamin C supplements to 500 mg/day as it can increase iron absorption 1, 2
• Avoid excess alcohol consumption, which can worsen liver damage 2

Clinical Benefits of Treatment

• Early treatment before development of cirrhosis and diabetes improves survival 2, 6
• Phlebotomy can improve insulin resistance in patients with hyperferritinemia 7
• Treatment can alleviate symptoms such as fatigue, weakness, and hyperpigmentation 6
• Liver function often improves with iron removal, as evidenced by decreasing ALT levels 4, 7

Pitfalls and Caveats

• Avoid overchelation by careful monitoring of ferritin levels 2
• Despite good tolerance to phlebotomy, significant losses to follow-up may occur; providing patients with an estimated number of phlebotomies needed may improve compliance 4
• Not all cases of hyperferritinemia represent true iron overload; confirm with transferrin saturation before initiating treatment 2, 8
• Phlebotomy should be postponed if anemia develops until resolved 2