What are the treatments for hyperferritinemia (elevated ferritin levels)?

From the Guidelines

To lower high ferritin levels, the most effective approach is therapeutic phlebotomy, which involves removing blood regularly (typically 400-500ml every 1-2 weeks) until ferritin levels normalize, with a target range of 50-100 lg/L, as recommended by the most recent guidelines 1.

Key Considerations

• Therapeutic phlebotomy is the mainstay of treatment for hereditary hemochromatosis and should be performed weekly or biweekly until iron stores are depleted, with a target serum ferritin of 50 lg/L, but not lower to avoid iron deficiency 1.
• During the maintenance phase, serum ferritin can be maintained with some flexibility in the range of 50-100 lg/L, and phlebotomy can be performed every 1-4 months, depending on the patient’s iron status 1.
• Serum haemoglobin should always be monitored during both induction and maintenance phases, and if haemoglobin concentrations are <12 g/dl, the frequency of phlebotomy should be decreased, and in specific cases, a reduction in volume should be considered 1.
• Serum ferritin should always be monitored to ensure that the target value is achieved and maintained, and to avoid overtreatment, with measurements every month during the induction phase and every 6 months during the maintenance phase 1.

Additional Recommendations

• Dietary modifications are not necessary, but avoiding vitamin C supplements and iron supplements is recommended, as vitamin C can accelerate mobilization of iron and increase pro-oxidant activity 1.
• Certain medications, such as chelators like deferasirox, deferiprone, or deferoxamine, may be considered in specific situations, but their use should be individualized and monitored closely 1.
• The underlying cause of high ferritin should be addressed, and regular monitoring of ferritin levels is essential during treatment, with target levels typically below 50-100 ng/mL for hemochromatosis patients 1.

From the FDA Drug Label

Monitor serum ferritin monthly and adjust the dose of deferasirox tablets, if necessary, every 3 to 6 months based on serum ferritin trends Use the minimum effective dose to achieve a trend of decreasing ferritin Adjust dose based on serum ferritin levels o If the serum ferritin falls below 1000 mcg/L at 2 consecutive visits, consider dose reduction, especially if the deferasirox tablets dose is greater than 17.5 mg/kg/day o If the serum ferritin falls below 500 mcg/L, interrupt deferasirox tablets therapy and continue monthly monitoring.

Lowering high ferritin can be achieved by using deferasirox tablets, with the goal of achieving a trend of decreasing ferritin levels. The dose should be adjusted based on serum ferritin levels, with consideration of dose reduction if ferritin levels fall below 1000 mcg/L at 2 consecutive visits. If ferritin levels fall below 500 mcg/L, therapy should be interrupted and monthly monitoring continued 2.

• Key points to consider when lowering high ferritin:
  • Monitor serum ferritin monthly
  • Adjust dose based on serum ferritin trends
  • Use the minimum effective dose to achieve a trend of decreasing ferritin
  • Consider dose reduction if ferritin levels fall below 1000 mcg/L at 2 consecutive visits
  • Interrupt therapy if ferritin levels fall below 500 mcg/L

From the Research

Lowering High Ferritin Levels

• High ferritin levels can be indicative of iron overload, which can cause multiple organ damage 3, 4.
• Iron chelation therapy (ICT) is a treatment option for patients with iron overload, and it has been shown to decrease serum ferritin levels and improve hematopoiesis 3, 4.
• Deferasirox is an oral iron chelator that has been used to treat iron overload in patients with transfusion-dependent anemias, and it has been shown to reduce serum ferritin levels 4, 5.
• The optimal serum ferritin level range is still a topic of debate, but some studies suggest that levels between 20-100 ng/mL may be associated with reduced mortality and improved outcomes 6.
• Ferritin is also an acute-phase protein, and its levels can be elevated in inflammation and infection, which can make it difficult to interpret ferritin levels as a diagnostic test for iron deficiency and overload 7.

Treatment Options

• Iron chelation therapy with deferasirox or deferiprone can be effective in reducing serum ferritin levels and improving outcomes in patients with iron overload 3, 4, 5.
• Phlebotomy can also be used to reduce iron stores and lower ferritin levels, especially in patients with peripheral arterial disease 6.
• It is essential to monitor serum ferritin levels and adjust treatment accordingly to achieve optimal outcomes 4, 5.

Diagnostic Considerations

• Serum ferritin concentration can be used as a diagnostic test for iron deficiency and overload, but its accuracy can be affected by inflammation and infection 7.
• The diagnostic odds ratio for ferritin as a test for iron deficiency is relatively high, but the evidence is still limited, and more studies are needed to confirm its accuracy 7.
• The optimal threshold for ferritin levels is still a topic of debate, and more research is needed to determine the best cutoff values for different populations 7.