What is the treatment for hemochromatosis?

Treatment of Hemochromatosis

Therapeutic phlebotomy is the primary treatment for hemochromatosis, with weekly removal of 500 mL of blood until serum ferritin reaches 50-100 μg/L, followed by lifelong maintenance phlebotomy to keep ferritin in this target range. 1, 2

Indications to Initiate Treatment

Begin phlebotomy when serum ferritin is ≥300 μg/L in men or ≥200 μg/L in women, regardless of symptoms. 3 This threshold-based approach prevents organ damage and improves long-term outcomes. Treatment is particularly straightforward for patients with liver disease or other end-organ manifestations, but even asymptomatic C282Y homozygotes with elevated ferritin should be treated prophylactically because the therapy is safe, inexpensive, and prevents complications. 1, 3

Induction Phase Protocol

Phlebotomy Schedule

• Remove 500 mL of blood weekly or biweekly as tolerated 1, 2
• Check hemoglobin/hematocrit before each session and do not allow it to drop more than 20% from baseline 1, 2
• Continue until serum ferritin reaches 50-100 μg/L 1, 2

Monitoring During Induction

• Measure serum ferritin every 10-12 phlebotomies (approximately every 3 months) 1, 2
• As ferritin approaches the 50-100 μg/L target, increase testing frequency to avoid inducing iron deficiency 1
• Each unit of blood removes approximately 200-250 mg of iron 1
• Patients with total body iron stores >30 g may require 2-3 years of weekly phlebotomy to achieve adequate iron depletion 1

Maintenance Phase

After reaching target ferritin of 50-100 μg/L, continue periodic phlebotomy to maintain ferritin in this range. 1, 2 The frequency varies substantially between individuals due to different rates of iron reaccumulation—some patients require monthly phlebotomy while others need only 1-2 units removed per year. 1 Not all patients reaccumulate iron and may not require maintenance therapy, so monitor ferritin levels to determine individual needs. 1

Dietary and Supplement Modifications

• Avoid vitamin C supplements entirely, especially during active phlebotomy, as pharmacologic doses accelerate iron mobilization and can saturate transferrin, increasing oxidative stress and free radical activity 1, 2
• Avoid medicinal iron and mineral supplements 4
• Avoid raw shellfish due to risk of Vibrio vulnificus infection in iron-overloaded patients 1, 4
• No specific low-iron diet is necessary, as dietary modification can only reduce iron absorption by 2-4 mg/day compared to 250 mg/week removed by phlebotomy 1

Special Clinical Situations

Patients with Advanced Cardiac Disease

Patients with cardiac arrhythmias or cardiomyopathy face increased risk of sudden death with rapid iron mobilization due to toxic low-molecular-weight iron chelates. 1, 3 Consider slower phlebotomy schedules or alternative therapies in these cases. 2

Patients Unable to Tolerate Phlebotomy

• Deferoxamine (Desferal) 20-40 mg/kg/day subcutaneously is effective for secondary iron overload or when phlebotomy is contraindicated 1, 2, 5
• Deferasirox (Exjade) can be given orally as an alternative chelator 1
• Erythrocytapheresis removes up to 1000 mL of red cells per session (versus 250 mL with phlebotomy), reducing treatment duration by approximately 70% and may be considered based on availability and patient preference 3, 6

Advanced Liver Disease

• Advanced cirrhosis is not reversed by iron removal 1
• Decompensated liver disease is an indication for liver transplantation evaluation 1
• Continue hepatocellular carcinoma screening in cirrhotic patients even after successful iron depletion, as cancer risk persists 3

Expected Clinical Improvements

Symptoms likely to improve with phlebotomy include malaise, fatigue, skin hyperpigmentation, insulin requirements in diabetics, and abdominal pain. 3 However, arthropathy, hypogonadism, and established cirrhosis respond poorly or not at all to treatment. 3

Common Pitfalls to Avoid

• Do not induce iron deficiency—stop phlebotomy when ferritin reaches 50-100 μg/L, not lower 1
• Excessive phlebotomy can cause symptomatic iron deficiency with anemia, hypochromia, and microcytosis that may persist for months 7
• Monitor hemoglobin and ferritin regularly to prevent over-treatment 7
• In the United States, blood from therapeutic phlebotomy can be used for transfusion donation at some institutions, providing societal benefit 1