What are the management strategies for Hereditary Hemochromatosis (HH) with iron overload?

From the Guidelines

Therapeutic phlebotomy is the first-line treatment for iron overload management, with a target ferritin level of 50-100 lg/L, as recommended by the most recent guidelines 1.

Iron Overload Management

Iron overload management is crucial to prevent morbidity and mortality associated with excess iron. The primary goal of treatment is to reduce iron stores to a safe level, thereby preventing organ damage.

Therapeutic Phlebotomy

• Therapeutic phlebotomy is the first-line treatment for iron overload management, removing 500ml of blood (containing approximately 200-250mg of iron) weekly until ferritin levels reach 50-100 ng/mL, followed by maintenance phlebotomy every 2-4 months 1.
• The target for iron depletion during induction is a serum ferritin of 50 lg/L, but not lower to avoid iron deficiency 1.
• In the maintenance phase, serum ferritin can be maintained with some flexibility in the range of 50-100 lg/L 1.

Iron Chelation Therapy

• For patients who cannot tolerate phlebotomy or have transfusion-dependent anemias, iron chelation therapy is recommended 1.
• Deferoxamine (Desferal) is administered subcutaneously or intravenously at 20-40 mg/kg/day over 8-24 hours.
• Oral alternatives include deferasirox (Exjade/Jadenu) at 20-40 mg/kg/day and deferiprone (Ferriprox) at 75-100 mg/kg/day divided into three doses.

Dietary Modifications

• Dietary modifications should not substitute for iron removal therapy 1.
• Iron supplementation should be avoided, and iron-fortified food should be avoided where possible 1.
• Supplemental vitamin C should be avoided, especially before iron depletion 1.
• Red meat consumption should be limited, and alcohol intake should be restricted during the iron depletion phase of treatment 1.

Monitoring and Follow-up

• Treatment efficacy is monitored through regular serum ferritin measurements, transferrin saturation, and organ-specific assessments like cardiac MRI T2* for heart iron and liver MRI for hepatic iron 1.
• Patients with haemochromatosis and cirrhosis should undergo HCC screening every 6 months, regardless of iron depletion 1.

From the FDA Drug Label

Deferasirox Tablets for Oral Suspension Deferasirox Tablets Transfusion-Dependent Iron Overload Starting Dose 20 mg/kg/day 14 mg/kg/day Titration Increments 5 mg/kg to 10 mg/kg 3. 5 mg/kg to 7 mg/kg Maximum Dose 40 mg/kg/day 28 mg/kg/day

Iron Overload Management:

• The management of iron overload involves the use of iron chelators such as deferasirox and deferoxamine.
• Deferasirox is administered orally, with a starting dose of 14 mg/kg/day for transfusion-dependent iron overload, and a maximum dose of 28 mg/kg/day.
• Deferoxamine is administered subcutaneously or intravenously, with a recommended dose of 40 mg/kg/day to 50 mg/kg/day over 8 hours to 12 hours for adults, and 20 mg/kg/day to 40 mg/kg/day over 8 hours to 12 hours for pediatric patients.
• Vitamin C may be given as an adjuvant to iron chelation therapy, in doses up to 200 mg for adults and 50 mg to 100 mg for pediatric patients, to increase the availability of iron for chelation 2, 3.

From the Research

Iron Overload Management

• Iron overload can lead to end-organ failure and death if left untreated, making timely diagnosis and management crucial 4.
• Phlebotomy is a simple and effective intervention for preventing or reversing organ damage from iron overload in patients with hereditary haemochromatosis 4.
• Deferasirox has been shown to be well-tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis, and could be a safe alternative to phlebotomy in selected patients 5.

Chelation Therapy

• Chelators such as deferoxamine, deferiprone, and deferasirox can affect both iron absorption and excretion, and have been used effectively in reversing the toxic side effects of iron overload 6.
• Combined subcutaneous (deferoxamine) and oral (deferiprone) treatment seems to hold particular promise for iron mobilization using chelation and phlebotomy 7.
• Iron chelation therapy is required in the treatment of many patients who have combined secondary and transfusional iron overload due to disorders in erythropoiesis 8.

Treatment Options

• Phlebotomy is the initial treatment of choice in haemochromatosis, while chelation is a mainstay in the treatment of transfusional siderosis 7.
• Deferoxamine treatment has been shown to be effective in preventing iron-induced tissue injury and in prolonging life expectancy in patients with beta-thalassemia who undergo regular transfusions 8.
• The use of oral chelators such as deferiprone and deferasirox has shown promise, but work is continuing on the development of new orally effective iron chelators 7, 8.