What is the treatment approach for iron overload conditions like hemochromatosis according to Davidson's book?

Treatment Approach for Iron Overload Conditions like Hemochromatosis

Therapeutic phlebotomy is the primary treatment for iron overload conditions like hemochromatosis, with a target ferritin level of 50-100 μg/L to reduce morbidity and mortality. 1

Initial Treatment Phase

• Weekly phlebotomy (removal of 400-500 ml of blood, equivalent to 200-250 mg iron) is the cornerstone of treatment for patients with hemochromatosis showing evidence of iron overload 1
• Phlebotomy should be performed until serum ferritin levels reach 50-100 μg/L 1, 2
• Adequate hydration before and after treatment and avoiding vigorous physical activity for 24 hours after phlebotomy is recommended 1
• Monitor hemoglobin levels before each phlebotomy session; consider reducing frequency if hemoglobin falls below 12 g/dL 2
• During treatment, dietary adjustments are unnecessary, but vitamin C supplements and iron supplements should be avoided 1, 2

Maintenance Phase

• After achieving target ferritin levels, patients require maintenance phlebotomy to prevent reaccumulation of iron 1, 3
• Frequency of maintenance phlebotomy should be individualized based on ferritin levels, typically ranging from every 2-4 months 3
• Regular monitoring of ferritin levels (every 3-4 months) is essential to adjust phlebotomy frequency 3
• Target maintenance ferritin level remains 50-100 μg/L for optimal outcomes 1
• Avoid excessive phlebotomy as it can lead to symptomatic iron deficiency with fatigue, anemia, and microcytosis 4

Special Considerations

• Phlebotomy can be safely performed in patients with advanced fibrosis or cirrhosis 1
• Patients with end-organ damage due to iron overload should undergo regular phlebotomy to the same endpoints as those without organ damage 1
• Before initiating phlebotomy, patients should be assessed for complications including diabetes mellitus, joint disease, endocrine deficiency, cardiac disease, porphyria cutanea tarda, and osteoporosis 1
• Blood taken during phlebotomy can potentially be used for transfusion if there are no medical contraindications and the patient has consented 1

Treatment Response

• Certain clinical features respond well to phlebotomy: malaise, fatigue, skin pigmentation, insulin requirements for diabetics, and abdominal pain 1
• Other features respond less well or not at all: arthropathy, hypogonadism, and advanced cirrhosis 1
• Hepatic fibrosis and cirrhosis may show regression after adequate phlebotomy in some cases 1
• Patients with cirrhosis should continue to be screened for hepatocellular carcinoma even after adequate iron depletion 1

Alternative Treatments for Secondary Iron Overload

• For secondary iron overload associated with ineffective erythropoiesis (e.g., thalassemia), iron chelation therapy is the treatment of choice 1
• Deferoxamine is administered by continuous subcutaneous infusion at 40 mg/kg/day for 8-12 hours nightly, 5-7 nights weekly 1
• Deferasirox, an oral iron-chelating drug, has been approved for treatment of secondary iron overload due to ineffective erythropoiesis 1, 5
• Newer agents like rusfertide, a peptidic mimetic of hepcidin, show promise in reducing phlebotomy requirements in hemochromatosis patients 6

Monitoring Treatment Efficacy

• Monitor serum ferritin levels every 10-12 phlebotomies during initial treatment phase 3
• In patients with HFE-related hemochromatosis, serum ferritin reliably reflects iron burden during therapy 1
• In secondary iron overload, ferritin levels can be misleading; liver biopsy or specialized imaging may be necessary to assess iron reduction 1
• Transferrin saturation should be monitored alongside ferritin levels to guide therapy 2