What is the initial treatment for Hemochromatosis?

Initial Treatment for Hemochromatosis

Therapeutic phlebotomy is the mainstay of initial treatment for hemochromatosis with evidence of iron overload, consisting of weekly removal of one unit of blood until serum ferritin reaches 50-100 μg/L. 1, 2

Phlebotomy Protocol

• Initiate therapeutic phlebotomy in all patients with hemochromatosis who have evidence of iron overload, including asymptomatic individuals with homozygous HH and markers of iron overload 3
• Remove one unit of blood (450-500 mL, containing approximately 200-250 mg iron) weekly or biweekly as tolerated 3, 2
• Check hemoglobin/hematocrit before each phlebotomy to avoid reducing levels to <80% of starting value 3
• Monitor serum ferritin approximately every 10-12 phlebotomies (every 3 months) during initial treatment 3
• Continue phlebotomy until serum ferritin drops to 50-100 μg/L, indicating mobilization of excess iron stores 3, 2

Expected Treatment Duration and Monitoring

• In patients with significant iron overload (>30g), therapeutic phlebotomy may take 2-3 years to adequately reduce iron stores 3
• As ferritin approaches target range (50-100 μg/L), increase frequency of testing to avoid iron deficiency 3
• After achieving target ferritin levels, assess whether maintenance phlebotomy is needed, as not all patients reaccumulate iron at the same rate 3, 2

Clinical Benefits of Phlebotomy

• Early phlebotomy before development of cirrhosis and/or diabetes significantly reduces morbidity and mortality 3, 1

• Symptoms likely to improve with phlebotomy include:

  • Malaise and fatigue 3, 1
  • Skin pigmentation 3
  • Insulin requirements for diabetics 3
  • Abdominal pain 3
  • Sense of well-being and energy level 3
  • Cardiac function 3

• Symptoms less responsive to phlebotomy:

  • Arthropathy 3, 1
  • Hypogonadism 3
  • Advanced cirrhosis (no response) 3

Maintenance Therapy

• After achieving target ferritin levels, continue less frequent phlebotomies (typically 2-6 times per year) to maintain serum ferritin between 50-100 μg/L 2
• Monitor ferritin and transferrin saturation every 6 months during maintenance phase 2
• Lifelong follow-up is required to prevent reaccumulation of iron 2

Alternative Treatments

• Erythrocytapheresis can be considered as an alternative to phlebotomy in select cases, with potential advantages of fewer procedures and shorter treatment duration 2, 4
• Iron chelation therapy with deferasirox is a second-line option only when phlebotomy is not possible 1, 2
• Deferasirox should not be used in patients with advanced liver disease or severe renal impairment (eGFR <40 mL/min/1.73m²) 5

Important Considerations and Pitfalls

• Avoid inducing iron deficiency through excessive phlebotomy, which can cause symptoms and anemia 6
• Patients with cirrhosis should continue to be screened for hepatocellular carcinoma (HCC) even after adequate phlebotomy, as HCC accounts for approximately 30% of HH-related deaths 3, 1
• Patient compliance with phlebotomy therapy tends to decrease over time, with an average decline of 6.8% annually 7
• Dietary modifications should supplement but not replace phlebotomy therapy 2, 8
• Patients should avoid iron supplements, vitamin C supplements, and limit alcohol intake 2, 8