What is the initial treatment for hemochromatosis?

Initial Treatment for Hemochromatosis

Therapeutic phlebotomy is the first-line treatment for hemochromatosis with iron overload, performed weekly or biweekly until serum ferritin reaches 50 μg/L. 1, 2

Indications to Initiate Treatment

Treatment should begin when specific ferritin thresholds are met:

• Men: Serum ferritin ≥300 μg/L 2, 3
• Women (premenopausal): Serum ferritin ≥200 μg/L 2, 3
• Postmenopausal women: Serum ferritin ≥300 μg/L 3

These thresholds apply regardless of whether symptoms are present. 2, 3 For C282Y homozygotes with ferritin <1000 μg/L and normal liver enzymes, proceed directly to phlebotomy without liver biopsy. 2, 3

Induction Phase Protocol

Remove one unit of blood (450-500 mL) weekly or biweekly until target ferritin is achieved: 1, 2

Hemoglobin Monitoring

• Check hemoglobin/hematocrit before every phlebotomy 2, 3
• If hemoglobin <12 g/dL: Reduce phlebotomy frequency 1, 2
• If hemoglobin <11 g/dL: Pause treatment entirely 1, 2
• Do not allow hemoglobin to drop more than 20% from baseline 2, 3

Ferritin Monitoring Strategy

• Check ferritin every 10-12 phlebotomies (approximately every 3 months) initially 3
• Once ferritin reaches 200 μg/L, increase monitoring to every 1-2 treatment sessions 1, 2
• Target ferritin for induction phase: 50 μg/L 1, 2

The EASL guidelines from 2022 provide the most comprehensive framework here, emphasizing that weekly phlebotomy remains standard despite being decades old because it is safe, effective, and inexpensive. 1

Maintenance Phase

After achieving iron depletion, lifelong maintenance therapy is required: 1, 2

• Frequency: Typically 2-6 phlebotomies per year 1, 2
• Target ferritin range: 50-100 μg/L 1, 2
• Check ferritin and transferrin saturation every 6 months 1, 2
• Continue hemoglobin monitoring before each phlebotomy 1

Patient compliance with maintenance therapy declines approximately 6.8% annually, so regular follow-up is essential. 4

Alternative Treatment Options

Erythrocytapheresis

This is a therapeutic alternative, not second-line therapy, with specific advantages: 1, 2

• Fewer procedures required: Reduces treatment burden by approximately 40% (1.9 vs 3.3 procedures per year) 5
• Shorter induction phase duration 1, 2
• Fewer hemodynamic changes compared to phlebotomy 1
• Preferred by 80% of patients 5
• More expensive per procedure but may be cost-effective due to fewer total procedures 1, 5

Use depends on local availability, expertise, and patient preference. 1, 3 Mild citrate reactions are common but manageable. 1

Iron Chelation Therapy

This is strictly second-line treatment, reserved only when phlebotomy is impossible: 1, 2

• Oral deferasirox is the most studied chelating agent 1, 2
• Requires careful risk-benefit assessment by a specialist due to adverse events 1, 2
• Contraindicated in advanced liver disease 2
• Target ferritin is higher than with phlebotomy 1
• May be necessary in severe juvenile hemochromatosis during induction 1

The FDA label for deferasirox specifies it should only be considered for transfusional iron overload with ferritin consistently >1000 mcg/L, making it inappropriate for typical hereditary hemochromatosis initial management. 6

Dietary and Lifestyle Modifications

These do not substitute for iron removal but are important adjuncts: 1, 2

• Avoid completely: Iron supplements, vitamin C supplements 1, 2, 3
• Limit: Daily red meat consumption, moderate to heavy alcohol intake 1, 2
• Patients with cirrhosis: Complete alcohol abstinence 1, 2
• Avoid: Raw or undercooked seafood (Vibrio vulnificus risk) 1, 2
• Avoid: Contact of wounds with seawater 1, 2

Proton pump inhibitors (when prescribed for other indications) can reduce phlebotomy requirements. 1, 2

Common Pitfalls to Avoid

Over-phlebotomy leading to iron deficiency: This occurs when ferritin and hemoglobin are not monitored appropriately. 7 If ferritin falls below 500 μg/L, interrupt therapy and monitor monthly. 1 Development of iron deficiency, anemia, or unexplained reduction in phlebotomy need should prompt workup for alternative causes. 1

Inadequate monitoring during maintenance: Compliance decreases over time, and patients may develop complications if iron reaccumulates. 4 Lifelong follow-up every 6 months is mandatory. 1, 2

Continuing phlebotomy in volume-depleted pediatric patients: Interrupt therapy during acute illnesses causing vomiting, diarrhea, or decreased oral intake, and resume only when volume status normalizes. 6

Expected Clinical Improvements

Certain manifestations improve with treatment: 3

• Malaise and fatigue
• Skin hyperpigmentation
• Insulin requirements in diabetics
• Abdominal pain

Manifestations that respond poorly or not at all: 3

• Arthropathy
• Hypogonadism
• Advanced cirrhosis (though phlebotomy prevents progression if started early)

Cirrhotic patients remain at risk for hepatocellular carcinoma despite successful iron depletion and require ongoing surveillance. 3