What is the treatment for hemochromatosis?

Treatment of Hemochromatosis

Therapeutic phlebotomy is the first-line treatment for hemochromatosis with iron overload, performed weekly or biweekly during the induction phase until serum ferritin reaches 50 μg/L, followed by lifelong maintenance phlebotomy to keep ferritin between 50-100 μg/L. 1, 2, 3

Induction Phase Protocol

Initial assessment before starting treatment:

• Obtain serum ferritin to quantify iron burden (treatment indicated when ferritin >1000 μg/L consistently with transfusion of ≥100 mL/kg packed red blood cells) 1, 2
• Measure serum creatinine in duplicate and calculate eGFR (contraindicated if eGFR <40 mL/min/1.73 m²) 4
• Check liver function tests, complete blood count, and renal tubular function (urinalysis, serum electrolytes) 2
• Perform baseline auditory and ophthalmic examinations 1

Phlebotomy regimen:

• Remove 450-500 mL of blood weekly or biweekly as tolerated 1, 2, 3
• Check hemoglobin/hematocrit before each session 1, 2, 3
• If hemoglobin <12 g/dL, reduce frequency; if <11 g/dL, pause treatment 1, 3
• Monitor ferritin every 10-12 phlebotomies initially, then every 1-2 sessions after ferritin reaches 200 μg/L 1, 3
• Target ferritin for iron depletion is 50 μg/L (not lower to avoid iron deficiency) 1, 3

Maintenance Phase Protocol

Lifelong maintenance is required to prevent iron reaccumulation:

• Continue phlebotomy typically 2-6 times per year to maintain ferritin between 50-100 μg/L 1, 3
• Check ferritin and transferrin saturation every 6 months 1, 3
• Monitor hemoglobin before each maintenance phlebotomy 1
• Patients with uncomplicated hemochromatosis can be accepted as regular blood donors during maintenance 1

Alternative Treatment Options

Erythrocytapheresis as an alternative to phlebotomy:

• Removes up to 1000 mL of red blood cells per session (versus 250 mL with phlebotomy), resulting in fewer procedures and shorter treatment duration in the induction phase 1, 3, 5
• More cost-effective when personalized based on sex, body weight, and hematocrit 1
• Causes fewer hemodynamic changes compared to phlebotomy 1
• Mild citrate reactions are common 1
• Target ferritin remains 50 μg/L for induction, 50-100 μg/L for maintenance 1

Iron chelation therapy (second-line):

• Reserved for patients who cannot tolerate phlebotomy after careful risk-benefit assessment 1, 3
• Deferasirox (oral) is the most studied option but carries significant risks including renal failure, hepatic failure, and gastrointestinal hemorrhage 1, 4
• Contraindicated in patients with advanced liver disease (Child-Pugh C) and requires dose reduction in moderate hepatic impairment (Child-Pugh B) 4
• Not approved by the European Medicines Agency for hemochromatosis treatment 1
• Deferoxamine 20-40 mg/kg/day subcutaneously is the traditional chelation option 2
• Target ferritin is higher with chelation compared to phlebotomy 1

Dietary and Lifestyle Modifications

Critical dietary restrictions (these do NOT substitute for iron removal therapy): 1, 3

• Avoid iron supplements and iron-fortified foods entirely 1, 3
• Avoid vitamin C supplements completely, especially during iron depletion, as vitamin C accelerates iron mobilization and increases oxidative stress 1, 2, 3
• Limit daily red meat consumption 1, 3
• Restrict alcohol intake during iron depletion; patients with cirrhosis must abstain completely 1, 3
• Avoid raw or undercooked seafood due to risk of Vibrio vulnificus infection, particularly in patients with iron overload 1, 3, 6
• Avoid contact of wounds with seawater (risk of siderophilic pathogen infection) 1

Helpful considerations:

• Proton pump inhibitors (when prescribed for other indications) can reduce phlebotomy requirements 1
• Consume fruit juices and citrus fruits in moderation, not in combination with other foods 1

Special Populations and Monitoring

Patients with cirrhosis:

• Should undergo regular screening for hepatocellular carcinoma (HCC), as the risk persists even after iron depletion 1
• Iron removal does not reverse established cirrhosis 3
• Decompensated liver disease may require liver transplantation 3

Monitoring parameters during treatment:

• Development of iron deficiency, anemia, or unexplained reduction in phlebotomy need should prompt complete workup for alternative causes 1
• Monitor for overchelation, particularly in pediatric patients with ferritin <1000 μg/L receiving higher doses 4

Common pitfall: Excessive phlebotomy can cause symptomatic iron deficiency with persistent anemia, microcytosis, and hypochromia lasting months 7. This is prevented by monitoring hemoglobin and ferritin levels appropriately and maintaining target ferritin at 50-100 μg/L rather than depleting to undetectable levels 1, 7.