What is the management of markedly elevated ferritin (iron storage protein) levels?

From the Guidelines

Therapeutic phlebotomy is the primary treatment for very high ferritin levels, aiming to reduce serum ferritin to a target range of 50-100 lg/L, as recommended by the most recent guidelines 1.

Management of Very High Ferritin Levels

The management of very high ferritin levels involves identifying and treating the underlying cause, which could be iron overload disorders like hemochromatosis, inflammatory conditions, liver disease, or certain cancers.

• The primary treatment for iron overload is therapeutic phlebotomy (blood removal), typically 400-500ml every 1-2 weeks until ferritin levels normalize, followed by maintenance phlebotomies 1.
• For those who cannot tolerate phlebotomy, iron chelation therapy with medications like deferasirox, deferoxamine, or deferiprone may be used.
• Dietary modifications include limiting iron-rich foods, vitamin C (which enhances iron absorption), and alcohol (which can worsen liver damage).
• Regular monitoring of ferritin levels, liver function, and cardiac status is essential, with serum ferritin measured every month during the induction phase and every 6 months during the maintenance phase 1.

Key Considerations

• Target ferritin levels: The target range for serum ferritin is 50-100 lg/L, as recommended by the EASL clinical practice guidelines on haemochromatosis 1.
• Phlebotomy frequency: The frequency of phlebotomy depends on the patient's iron status, with weekly or fortnightly phlebotomy during the induction phase and every 1-4 months during the maintenance phase 1.
• Monitoring: Serum haemoglobin should be monitored during both induction and maintenance phases, and phlebotomy should be discontinued if haemoglobin concentrations are <11 g/dl 1.
• Iron chelation therapy: Iron chelation therapy may be used for patients who cannot tolerate phlebotomy, with medications like deferasirox, deferoxamine, or deferiprone 1.

From the FDA Drug Label

The recommended initial dose of deferasirox tablets for patients 2 years of age and older with eGFR greater than 60 ml/min/1. 73 m2 is 14 mg per kg body weight orally, once daily. During Therapy: 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 Make dose adjustments in steps of 3.5 or 7 mg per kg and tailor adjustments to the individual patient’s response and therapeutic goals. In patients not adequately controlled with doses of 21 mg per kg (e.g., serum ferritin levels persistently above 2500 mcg/L and not showing a decreasing trend over time), doses of up to 28 mg per kg may be considered.

Management of Very High Ferritin Levels:

• The dose of deferasirox should be adjusted based on serum ferritin levels.
• If serum ferritin levels are persistently above 2500 mcg/L, doses of up to 28 mg per kg may be considered.
• The minimum effective dose should be used to achieve a trend of decreasing ferritin.
• Dose adjustments should be made in steps of 3.5 or 7 mg per kg, tailored to the individual patient's response and therapeutic goals 2.

From the Research

Management of Very High Ferritin Levels

• Very high ferritin levels can be managed using iron chelation therapy, which helps remove excess iron from the body 3, 4, 5, 6, 7
• Deferasirox is an effective oral chelator that can reduce serum ferritin levels and labile plasma iron in patients with iron overload 3, 4, 5, 6, 7
• The efficacy of deferasirox depends on the dose and ratio compared to other chelators such as deferoxamine 3
• Combination therapy with deferiprone and deferasirox may be effective in patients with β-thalassemia major who have suboptimal response to monotherapy 6
• Deferasirox has been shown to reduce serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome 7

Safety and Efficacy of Deferasirox

• Deferasirox is generally well-tolerated, with common adverse events including gastrointestinal disturbances and increased serum creatinine 3, 4, 5, 6, 7
• The safety and efficacy of deferasirox have been demonstrated in various studies, including those in patients with thalassemia major, hereditary hemochromatosis, and myelodysplastic syndrome 3, 4, 5, 6, 7
• Patient satisfaction and adherence to deferasirox therapy are important factors to consider in the management of very high ferritin levels 3

Comparison with Other Chelators

• Deferasirox has been compared to other chelators such as deferoxamine and deferiprone in various studies 3, 5, 6
• The choice of chelator depends on individual patient factors, including the severity of iron overload, renal function, and patient preference 3, 5, 6