What is the management of hereditary hemochromatosis?

Management of Hereditary Hemochromatosis

Therapeutic phlebotomy is the cornerstone of hereditary hemochromatosis (HH) management and should be initiated in all patients with evidence of iron overload to prevent morbidity and mortality. 1

Initial Assessment and Diagnosis

Before initiating treatment, patients should be evaluated for:

• Serum ferritin and transferrin saturation levels
• Evidence of end-organ damage (liver enzymes, glucose, cardiac function)
• Presence of cirrhosis (which affects prognosis and surveillance needs)
• HFE gene mutation status (C282Y homozygosity being most common)

Treatment Protocol

Initial Iron Depletion Phase

• Weekly phlebotomy: Remove 500 mL of blood (containing 200-250 mg iron) weekly or biweekly as tolerated 1
• Pre-phlebotomy monitoring: Check hemoglobin/hematocrit before each session
• Safety parameters: Do not allow hemoglobin/hematocrit to fall by more than 20% of previous level 1
• Progress monitoring: Check serum ferritin every 10-12 phlebotomies (approximately every 3 months) 1
• Target: Continue until serum ferritin reaches 50-100 μg/L 1

Maintenance Phase

• Individualized frequency: Schedule maintenance phlebotomies based on rate of iron reaccumulation
  • Some patients require monthly phlebotomy
  • Others may need only 1-2 phlebotomies per year 1
• Target: Maintain serum ferritin between 50-100 μg/L 1
• Duration: Lifelong maintenance therapy is required 1

Special Considerations

Advanced Disease

• Cardiac involvement: Patients with cardiac arrhythmias or cardiomyopathy are at increased risk of sudden death with rapid iron mobilization 1
• Cirrhosis: Patients with cirrhosis should undergo regular screening for hepatocellular carcinoma (HCC) even after iron depletion 1
• Decompensated liver disease: Consider liver transplantation evaluation 1

Dietary and Supplement Recommendations

• Vitamin C: Avoid vitamin C supplements as they can increase iron absorption and mobilization, potentially causing toxicity during treatment 1
• Iron supplements: Should be avoided 1
• Raw shellfish: Avoid due to risk of Vibrio vulnificus infection in iron-overloaded patients 1
• Regular diet: No specific dietary restrictions are necessary as the amount of iron absorption affected by diet is minimal (2-4 mg/day) compared to phlebotomy (250 mg/week) 1

Expected Treatment Response

Phlebotomy treatment can improve:

• Fatigue and malaise
• Skin pigmentation
• Insulin requirements in diabetics
• Abdominal pain
• Liver enzymes
• Hepatic fibrosis (in approximately 30% of cases if treated early) 1

Conditions less responsive or unresponsive to phlebotomy:

• Arthropathy
• Hypogonadism
• Advanced cirrhosis 1

Alternative Treatment Options

For patients who cannot tolerate conventional phlebotomy, therapeutic erythrocytapheresis (TE) may be considered:

• Allows removal of up to 1000 mL of erythrocytes per session (vs. 250 mL with phlebotomy)
• May reduce total number of treatments by up to 70% 2
• May shorten overall treatment duration 2

Blood Donation Considerations

Blood obtained through therapeutic phlebotomy from HH patients is generally considered safe for transfusion in the United States, as supported by both the American Red Cross and the FDA 1, 3

Monitoring and Follow-up

• Regular monitoring of serum ferritin levels to guide maintenance therapy
• For patients with cirrhosis: ongoing surveillance for HCC even after iron depletion 1
• Periodic assessment of end-organ function (liver, heart, pancreas) as clinically indicated

Clinical Pitfalls to Avoid

• Delayed treatment: Early treatment before development of cirrhosis and diabetes significantly reduces morbidity and mortality 1
• Excessive phlebotomy: Avoid causing iron deficiency (ferritin <50 μg/L) 1
• Inadequate monitoring: Failure to adjust maintenance phlebotomy frequency based on individual iron reaccumulation rates
• Vitamin C supplementation: Can cause rapid iron mobilization and potential toxicity 1
• Overlooking HCC risk: Patients with cirrhosis remain at risk for HCC even after iron depletion 1

By following this systematic approach to management, patients with hereditary hemochromatosis can achieve normal life expectancy when diagnosed and treated before the development of cirrhosis or diabetes.