What is the treatment for hemochromatosis?

Treatment of Hemochromatosis

First-Line Treatment: Therapeutic Phlebotomy

Therapeutic phlebotomy is the definitive first-line treatment for hemochromatosis with iron overload, and should be initiated in all patients with serum ferritin ≥300 μg/L in men or ≥200 μg/L in women to prevent organ damage and improve survival. 1, 2

Induction Phase Protocol

• Remove 500 mL (one unit) of blood weekly or biweekly, continuing until serum ferritin reaches the target of 50 μg/L 1, 2
• Check hemoglobin/hematocrit before each phlebotomy session 1, 2
• If hemoglobin drops below 12 g/dL, reduce the frequency of phlebotomy 1
• If hemoglobin falls below 11 g/dL, pause treatment temporarily 1, 2
• Monitor serum ferritin every 10-12 phlebotomies initially, then check every 1-2 treatment sessions once ferritin reaches 200 μg/L 1, 2
• Do not allow hemoglobin to decrease by more than 20% from baseline 2, 3

Maintenance Phase Protocol

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

Pre-Treatment Assessment

Before initiating phlebotomy, obtain baseline measurements including: 2, 3

• Serum ferritin level to quantify iron burden
• Liver function tests (ALT, AST, bilirubin) to assess hepatic involvement 1
• Complete blood count to ensure adequate hemoglobin for phlebotomy
• Serum creatinine in duplicate and calculate eGFR to establish renal function 1, 3
• Baseline auditory and ophthalmic examinations 2

Alternative Treatment Options

Erythrocytapheresis

• Consider erythrocytapheresis as an alternative to standard phlebotomy, particularly when faster iron removal is desired 1, 2
• Removes up to 1000 mL of red blood cells per session compared to 250 mL with phlebotomy, reducing total number of procedures by approximately 70% and shortening treatment duration 1, 5
• Results in fewer hemodynamic changes compared to phlebotomy 1
• Mild citrate reactions are more common with this approach 1
• Use the same target ferritin levels: 50 μg/L for induction, 50-100 μg/L for maintenance 1
• Availability depends on local expertise and patient preferences 1

Iron Chelation Therapy (Second-Line)

Iron chelation should only be used as second-line therapy when phlebotomy is not possible, and requires careful risk assessment by a specialist due to significant adverse events. 1, 2

• Deferasirox is the most studied oral chelation agent, but is not approved for hemochromatosis by regulatory agencies and carries black box warnings for renal failure, hepatic failure, and gastrointestinal hemorrhage 6
• Contraindicated in patients with eGFR <40 mL/min/1.73 m² and in those with advanced liver disease 6
• Deferoxamine 20-40 mg/kg/day subcutaneously is the traditional chelation option when phlebotomy cannot be tolerated 1, 3
• Target ferritin levels are higher with chelation compared to phlebotomy 1
• Combination therapy with phlebotomy/erythrocytapheresis is possible in selected cases 1

Dietary and Lifestyle Modifications

Dietary modifications do not substitute for iron removal therapy but serve as important adjunctive measures. 1, 4

Strict Avoidance

• Iron supplements and iron-fortified foods must be avoided entirely 1, 4
• Vitamin C supplements should be completely avoided, especially during active iron depletion, as vitamin C accelerates iron mobilization and increases oxidative stress 1, 3
• Raw or undercooked seafood must be avoided due to risk of Vibrio vulnificus infection, which can be fatal in iron-overloaded patients 1, 4
• Avoid contact of open wounds with seawater 1, 4

Moderation Recommendations

• Limit daily red meat consumption 1, 4
• Restrict alcohol intake; patients with advanced liver disease or cirrhosis should abstain completely 1, 4

Potential Benefits

• Proton pump inhibitors (when prescribed for other indications) can reduce phlebotomy requirements by decreasing iron absorption 1, 2

Special Populations and Considerations

Patients with Cirrhosis

• Advanced cirrhosis is not reversed by iron removal therapy 1, 4
• Regular screening for hepatocellular carcinoma (HCC) is mandatory, as HCC accounts for approximately 30% of hemochromatosis-related deaths 4
• Decompensated liver disease is an indication for liver transplantation evaluation 1
• Current survival after liver transplantation is comparable to other indications, provided adequate iron removal occurs before transplantation 1

Patients with Cardiac Involvement

• In patients with cardiomyopathy or arrhythmias, rapid iron mobilization increases risk of sudden death 3
• Consider a slower phlebotomy schedule or iron chelation in these high-risk patients 3

Elderly Patients

• Consider more relaxed ferritin targets during maintenance (up to 200 μg/L for women, 300 μg/L for men) 3

Patients Without Significant Liver Disease

• C282Y homozygotes with elevated ferritin <1000 μg/L and no indicators of significant liver disease (normal ALT, AST) can proceed directly to phlebotomy without liver biopsy 1, 2

Critical Monitoring Parameters

During Induction Phase

• Hemoglobin/hematocrit before each phlebotomy session 1, 2, 3
• Serum ferritin every 10-12 phlebotomies until 200 μg/L is reached, then every 1-2 sessions 1, 2
• Liver function tests every 2 weeks during the first month, then at least monthly 1

During Maintenance Phase

• Hemoglobin/hematocrit before each phlebotomy 1, 3
• Serum ferritin and transferrin saturation every 6 months 1
• Liver function tests periodically to assess for hepatic complications 3

Common Pitfalls to Avoid

• Overchelation: Development of iron deficiency anemia during treatment requires complete workup for alternative causes of blood loss 1, 7
• Excessive phlebotomy frequency: In pediatric patients receiving deferasirox doses >17.5 mg/kg/day when ferritin is <1000 μg/L, there is a 6-fold increased rate of renal adverse events 6
• Inadequate monitoring: An unexplained reduction in phlebotomy need should prompt investigation for occult bleeding or other pathology 1
• Premature discontinuation: Patient compliance with maintenance therapy declines at approximately 6.8% annually, requiring ongoing education and support 8

Blood Donation Eligibility

• Patients with uncomplicated hemochromatosis (without significant organ damage) can be accepted as regular blood donors during the maintenance phase 1
• Blood taken from hemochromatosis patients should be made available for transfusion when possible 1
• Patients should continue routine monitoring through their hemochromatosis service even when donating blood 1