What are the treatment options for elevated ferritin (iron) levels?

Management of Elevated Ferritin Levels

The primary treatment for elevated ferritin due to true iron overload is therapeutic phlebotomy, with weekly removal of 500 mL of blood until ferritin reaches 50-100 μg/L, followed by lifelong maintenance phlebotomy to keep ferritin in this target range. 1

Initial Diagnostic Evaluation

Before initiating treatment, you must distinguish true iron overload from hyperferritinemia due to other causes:

• Measure transferrin saturation (TSAT) as the critical first step—elevated TSAT (>45%) with elevated ferritin indicates true iron overload requiring treatment, while normal or low TSAT suggests inflammation, malignancy, or other secondary causes 1, 2
• Order HFE genetic testing (C282Y and H63D mutations) if TSAT is elevated to confirm hereditary hemochromatosis 2, 3
• Obtain baseline labs including complete blood count, liver function tests (ALT, AST), and renal function before starting phlebotomy 4
• Consider MRI with R2 quantification* to assess hepatic iron concentration if the diagnosis is unclear or if you need to quantify the degree of iron overload 1

The most common non-iron overload causes of elevated ferritin include malignancy, chronic liver disease, infection, kidney failure, and inflammatory conditions—these typically present with normal or low TSAT 5, 3

Treatment Protocol for Confirmed Iron Overload

Induction Phase

Perform weekly phlebotomy removing 500 mL of blood until serum ferritin reaches 50-100 μg/L 1, 4:

• Check hemoglobin/hematocrit before each session—do not proceed if hemoglobin drops more than 20% from baseline 1
• Monitor ferritin every 10-12 phlebotomies during the induction phase 1, 4
• Stop frequent phlebotomy when ferritin reaches 50-100 μg/L 1

For patients who cannot tolerate phlebotomy (severe anemia, cardiovascular instability), use iron chelation with deferoxamine 20-40 mg/kg/day subcutaneously or oral deferasirox 1, 6

Maintenance Phase

Continue phlebotomy every 2-4 months to maintain ferritin between 50-100 μg/L 1, 2, 4:

• Monitor ferritin monthly initially during maintenance, then adjust frequency based on stability 2, 4
• The goal is lifelong maintenance to prevent iron reaccumulation 1

Dietary and Lifestyle Modifications

Avoid vitamin C supplements entirely—vitamin C enhances iron absorption and mobilization, potentially worsening iron overload 1, 4:

• Avoid iron supplements and iron-fortified foods 2, 4
• Avoid raw shellfish due to risk of Vibrio vulnificus infection in iron-overloaded patients 1, 2
• Limit alcohol consumption as it increases risk of fibrosis and hepatocellular malignancy in iron overload 1, 2
• No specific low-iron diet is necessary as dietary restriction removes only 2-4 mg/day compared to 250 mg/week with phlebotomy 1

Special Populations and Contexts

Secondary Iron Overload

Phlebotomy is beneficial in certain secondary causes 1:

• Non-alcoholic fatty liver disease (NAFLD): Phlebotomy improves insulin resistance and reduces elevated ALT levels 1
• Porphyria cutanea tarda: Phlebotomy reduces skin manifestations 1
• Chronic hepatitis C: Phlebotomy reduces ALT but does not affect viral clearance; not recommended for mild iron overload (hepatic iron concentration <2,500 μg/g) 1
• Alcoholic liver disease: No evidence supports phlebotomy benefit 1

Patients with Cirrhosis

Liver biopsy is not recommended if cirrhosis is already clinically evident 1:

• Consider liver biopsy only if ferritin >1,000 μg/L or liver enzymes are elevated to assess fibrosis stage 1
• Proceed with phlebotomy even in cirrhotic patients with confirmed iron overload, targeting the same ferritin goals of 50-100 μg/L 7

Transfusion-Dependent Patients

Use iron chelation therapy rather than phlebotomy for secondary iron overload due to ineffective erythropoiesis (thalassemia, myelodysplastic syndrome) 1:

• Deferoxamine 20-40 mg/kg/day is the traditional choice 1, 6
• Oral deferasirox is an alternative but has safety concerns 1

Critical Monitoring Parameters

Track these parameters throughout treatment 1, 4:

• Hemoglobin/hematocrit before each phlebotomy session
• Serum ferritin every 10-12 phlebotomies during induction, then monthly during maintenance
• Liver function tests periodically to assess for hepatic complications
• Screen for hepatocellular carcinoma in patients with established cirrhosis 2

Common Pitfalls to Avoid

Do not treat elevated ferritin with phlebotomy if TSAT is normal or low—this indicates hyperferritinemia from inflammation or other causes, not true iron overload requiring iron removal 1, 2, 8:

• Ferritin is an acute phase reactant and can be falsely elevated in inflammation, infection, malignancy, and chronic liver disease 1, 5
• Iron supplementation with normal or high ferritin is potentially harmful 1

Do not exceed target ferritin of 50-100 μg/L—overchelation increases toxicity risk 1, 2:

• When ferritin falls below 1,000 ng/mL, toxicity risk increases and requires more careful monitoring 1
• In patients with genetic iron disorders requiring IV iron (IRIDA), do not exceed ferritin of 500 mg/L to avoid long-term toxicity 1

Do not perform phlebotomy if hemoglobin drops >20% from baseline—allow recovery before proceeding 1