What is the primary treatment for hemochromatosis?

Primary Treatment for Hemochromatosis

Therapeutic phlebotomy is the mainstay of treatment for hemochromatosis with evidence of iron overload and should be initiated in all patients to prevent complications and improve survival. 1

Treatment Protocol

• Phlebotomy therapy consists of two phases: induction and maintenance 1
• During induction phase, one unit of blood (450-500 mL) should be removed weekly or twice weekly as tolerated, with each phlebotomy preceded by measurement of hemoglobin/hematocrit 2
• Avoid reducing hemoglobin/hematocrit to less than 80% of the starting value during treatment 2
• Continue phlebotomy until serum ferritin drops to between 50-100 μg/L, indicating mobilization of excess iron stores 2, 1
• Monitor serum ferritin after every 10-12 phlebotomies (approximately every 3 months) during initial treatment 2
• In patients with significant iron overload (>30g total body iron), therapeutic phlebotomy may take 2-3 years to adequately reduce iron stores 2

Maintenance Phase

• After achieving target ferritin levels (50-100 μg/L), transition to maintenance phlebotomy 1
• The frequency of maintenance phlebotomy varies among individuals based on their rate of iron reaccumulation 2
• Not all patients with hemochromatosis reaccumulate iron at the same rate; some may not require maintenance phlebotomy 2
• Regular monitoring of serum ferritin is necessary to determine appropriate maintenance schedule 1

Clinical Benefits of Phlebotomy

• Early phlebotomy treatment significantly improves survival when initiated before development of cirrhosis and diabetes 1
• Phlebotomy effectively improves several clinical manifestations: 2, 1
  • Responsive symptoms: malaise, fatigue, skin pigmentation, insulin requirements for diabetics, abdominal pain
  • Less responsive: arthropathy, hypogonadism
  • Non-responsive: advanced cirrhosis, testicular atrophy

Special Considerations

• Hepatic fibrosis and cirrhosis may show regression after phlebotomy in approximately 30% of cases 2
• Patients with cirrhosis should continue to be screened for hepatocellular carcinoma (HCC) following phlebotomy, as HCC accounts for approximately 30% of hemochromatosis-related deaths 2, 1
• HCC is exceptionally rare in non-cirrhotic hemochromatosis, providing additional argument for preventive therapy prior to cirrhosis development 2
• Patient compliance with phlebotomy therapy tends to decrease over time, with an average annual decline of 6.8% in maintenance therapy adherence 3

Alternative Treatments

• Iron chelation therapy is a second-line option when phlebotomy is not possible 1, 4
• Deferasirox (DFX) is the most studied chelator but is not approved for hemochromatosis by the European Medicines Agency 1
• Chelation therapy should not be used in patients with advanced liver disease 1
• Deferoxamine mesylate is administered subcutaneously or intravenously over 10-12 hours/day when phlebotomy is contraindicated 4

Dietary and Lifestyle Recommendations

• Patients should avoid iron supplements and iron-fortified foods 1, 5
• Limit supplemental vitamin C, especially before iron depletion 1
• Restrict alcohol intake and avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection 1, 6
• Dietary management can reduce the rate of iron reaccumulation and help reduce complications 5

Therapeutic phlebotomy remains the cornerstone of hemochromatosis management, with recent understanding of the role of ferroptosis, reactive oxygen species, and gut microbiome in disease pathophysiology further supporting this approach 7.