What is the approach to managing high ferritin levels?

Approach to High Ferritin Levels

The management of high ferritin levels requires determining the underlying cause through transferrin saturation measurement, with therapeutic phlebotomy as the primary treatment for confirmed iron overload, targeting a serum ferritin level of 50-100 μg/L. 1, 2

Diagnostic Approach

• Determine if hyperferritinemia is due to iron overload or other causes by measuring transferrin saturation 1
• Consider genetic testing for hereditary hemochromatosis (HFE) 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
• Evaluate for secondary causes of iron overload such as transfusion-dependent anemias, which require different management approaches 3

Treatment Protocol for Iron Overload

Initial Therapy (Induction Phase)

• Initiate weekly therapeutic phlebotomy (removal of 400-500 mL blood) as tolerated by the patient 2, 1
• Monitor hemoglobin and hematocrit before each phlebotomy session to avoid excessive reduction 2
• Postpone phlebotomy if anemia develops (hemoglobin <11 g/dL) until resolved 2
• Check serum ferritin every 10-12 phlebotomies (approximately every 3 months) during initial therapy 2, 1
• Continue therapeutic phlebotomy until serum ferritin reaches the target of 50 μg/L 2

Maintenance Therapy

• After achieving target ferritin levels, continue maintenance phlebotomies to keep ferritin between 50-100 μg/L 2
• The frequency of maintenance phlebotomy varies among individuals (every 1-4 months), depending on the rate of iron reaccumulation 2, 1
• Monitor serum ferritin every 6 months during maintenance phase to adjust treatment schedule 2
• An alternative approach is to cease phlebotomy and monitor ferritin, restarting when ferritin reaches the upper limit of normal 2

Special Considerations

For Patients with Cirrhosis

• Patients with cirrhosis and iron overload should undergo therapeutic phlebotomy to reduce ferritin levels to 50-100 μg/L 4
• Monitor liver function tests regularly during treatment 4
• Avoid raw shellfish due to risk of Vibrio vulnificus infection 2, 4

For Patients with Transfusional Iron Overload

• Consider iron chelation therapy with deferasirox for patients with transfusion-dependent anemias 2, 3
• Initiate chelation when serum ferritin exceeds 1,000 ng/mL and the patient has received >120 mL/kg of red blood cells 5
• Monitor for potential adverse effects of chelation therapy, including renal dysfunction, hepatotoxicity, and cytopenias 3
• Adjust deferasirox dosing based on serum ferritin levels, with dose reduction if ferritin falls below 1,000 μg/L 3

Dietary and Lifestyle Modifications

• Avoid iron supplements and iron-fortified foods 2, 1
• Limit vitamin C supplements, which can increase iron absorption 2, 1
• Restrict alcohol intake, especially during the iron depletion phase and completely avoid if cirrhosis is present 2
• Maintain a broadly healthy diet rather than strict iron restriction 2

Monitoring and Follow-up

• Monitor serum ferritin monthly during initial therapy and every 3-6 months during maintenance 2, 1
• Perform regular screening for hepatocellular carcinoma in patients with cirrhosis 1
• Assess for improvement in organ function after iron depletion 2
• Be aware that certain clinical features, particularly arthralgia, may not improve with iron depletion 2

Common Pitfalls and Caveats

• Avoid overchelation by careful monitoring of ferritin levels 1
• Be aware that transferrin saturation may remain elevated even when serum ferritin is within target range in patients with hemochromatosis 2
• Recognize that early treatment before development of cirrhosis and diabetes improves survival to normal population levels 2, 1
• Understand that phlebotomy can be safely used in various conditions causing iron overload, including post-leukemia survivors 6