What are the management options for hemochromatosis?

Management of Hemochromatosis

Therapeutic phlebotomy is the cornerstone of hemochromatosis management, with weekly removal of 500 mL of blood until serum ferritin reaches 50-100 μg/L, followed by lifelong maintenance phlebotomy to prevent iron reaccumulation. 1

Initial Treatment Phase: Iron Depletion

Phlebotomy Protocol

• Remove 500 mL of blood weekly or biweekly as the patient tolerates, which removes approximately 250 mg of iron per session 1
• Check hemoglobin/hematocrit before each phlebotomy session and do not allow it to fall by more than 20% from the prior level 1, 2
• If hemoglobin drops below 12 g/dL, reduce the frequency of phlebotomy; if below 11 g/dL, pause treatment until recovery 2
• Monitor serum ferritin every 10-12 phlebotomies initially, then every 1-2 sessions once ferritin reaches 200 μg/L 1, 2
• Continue weekly phlebotomy until serum ferritin reaches 50-100 μg/L, which typically takes 6-7 months and 13-14 sessions in most patients 1, 3

When to Proceed Without Liver Biopsy

• C282Y homozygotes with elevated ferritin less than 1000 μg/L and no evidence of liver disease (normal ALT/AST) can proceed directly to phlebotomy without liver biopsy 1, 4
• Patients under 40 years of age without clinical liver disease and ferritin less than 1000 μg/L do not require biopsy before treatment 4

Maintenance Phase: Preventing Iron Reaccumulation

Long-Term Management

• Continue phlebotomy at reduced frequency (typically 2-6 times per year) to maintain serum ferritin between 50-100 μg/L 1, 2
• Monitor serum ferritin and transferrin saturation every 6 months during maintenance 2, 4
• Lifelong follow-up is mandatory as iron will reaccumulate without ongoing treatment 2

Common Pitfall: Overchelation

• Avoid excessive iron removal, which can cause symptomatic iron deficiency with fatigue, anemia, and microcytosis that may persist for months 5
• If ferritin falls below 50 μg/L, reduce phlebotomy frequency; if below 500 μg/L, interrupt therapy and monitor monthly 6, 7

Alternative Treatment Options

Erythrocytapheresis

• Consider erythrocytapheresis as an alternative to standard phlebotomy, particularly for patients who prefer fewer procedures 2
• Removes up to 1000 mL of red blood cells per session (approximately 500 mg iron), achieving iron depletion in 70% fewer sessions and shorter treatment duration 8, 3
• May be more cost-effective in the induction phase despite higher per-procedure costs 2, 8

Iron Chelation Therapy

• Iron chelation is second-line therapy reserved for patients who cannot tolerate phlebotomy (e.g., severe anemia, poor venous access) 1, 2
• Deferoxamine (Desferal) at 20-40 mg/kg/day via continuous subcutaneous infusion for 8-12 hours nightly, 5-7 nights weekly 1
• Deferasirox (Exjade) is an oral alternative approved for secondary iron overload due to transfusion-dependent anemias, but should not be used in patients with advanced liver disease due to hepatotoxicity risk 1, 7
• Phlebotomy remains the method of choice for hereditary hemochromatosis; chelation is not indicated as primary therapy 9

Dietary and Lifestyle Modifications

What to Avoid

• Avoid vitamin C supplements entirely, as pharmacological doses accelerate iron mobilization and may increase pro-oxidant activity 1
• Avoid iron supplements and iron-fortified foods 6
• Avoid raw or undercooked shellfish due to risk of fatal Vibrio vulnificus infection in iron-overloaded patients 1
• Limit red meat consumption and restrict alcohol intake; patients with cirrhosis should abstain from alcohol completely 2, 6

Dietary Adjustments

• No special low-iron diet is necessary during treatment, as dietary modification removes only 2-4 mg iron daily compared to 250 mg per phlebotomy 1
• Maintain a broadly healthy diet rather than strict iron restriction 6

Special Clinical Scenarios

Advanced Cirrhosis

• Iron removal does not reverse established cirrhosis, and decompensated liver disease is an indication for liver transplantation evaluation 1
• Adequate iron removal before transplantation is critical, as inadequate depletion historically led to perioperative cardiac and infectious complications 1
• Current survival after liver transplantation is comparable to other causes when iron is adequately removed pre-operatively 1

Patients with End-Organ Damage

• Continue regular phlebotomy to the same ferritin targets (50-100 μg/L) even in patients with established complications such as cirrhosis, diabetes, or cardiomyopathy 1
• While cirrhosis is not reversed, phlebotomy may improve fatigue, hepatic enzyme elevations, right upper quadrant pain, and hyperpigmentation 10

Monitoring for Hepatocellular Carcinoma

• Patients with cirrhosis require regular screening for hepatocellular carcinoma, as iron removal does not eliminate this risk 1, 6

Treatment Benefits and Prognosis

• Phlebotomy therapy improves survival and prevents complications when initiated before development of cirrhosis and diabetes 2, 6
• Early treatment before severe iron overload prevents hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy 10
• Survival approaches normal population levels when treatment begins before irreversible organ damage occurs 6

Key Monitoring Parameters

During Induction Phase

• Hemoglobin/hematocrit before each phlebotomy 1, 2
• Serum ferritin every 10-12 phlebotomies, then every 1-2 sessions as ferritin approaches 200 μg/L 1, 4

During Maintenance Phase

• Serum ferritin and transferrin saturation every 6 months 2, 4
• Liver function tests periodically in patients with liver disease 6