What is the first‑line treatment and management plan (including phlebotomy schedule, monitoring, and alternatives if phlebotomy is contraindicated) for an adult with elevated ferritin due to iron overload such as hereditary hemochromatosis?

Therapeutic Blood Donation for Elevated Ferritin

Weekly therapeutic phlebotomy (500 mL) is the first-line treatment for iron overload from hereditary hemochromatosis, targeting a ferritin level of 50-100 μg/L during induction, followed by lifelong maintenance phlebotomy to prevent iron reaccumulation. 1

Induction Phase Protocol

Begin weekly phlebotomy immediately for patients with confirmed hemochromatosis and elevated ferritin, removing 500 mL of blood per session until ferritin reaches 50-100 μg/L. 1, 2

Pre-Phlebotomy Monitoring

• Check hemoglobin/hematocrit before every single session to prevent excessive anemia 1, 3
• If hemoglobin drops below 12 g/dL: reduce phlebotomy frequency 1
• If hemoglobin drops below 11 g/dL: pause treatment entirely 1
• Allow hemoglobin to fall by no more than 20% from baseline 1

Ferritin Monitoring Schedule

• Check ferritin every 10-12 phlebotomies during initial treatment 1, 2
• Once ferritin reaches 200 μg/L, increase monitoring to every 1-2 treatment sessions 1, 4
• Stop weekly phlebotomy when ferritin reaches 50-100 μg/L 1

Treatment Decisions Based on Baseline Ferritin

• Ferritin <1000 μg/L without liver enzyme elevation: Proceed directly to phlebotomy without liver biopsy 1, 3
• Ferritin ≥1000 μg/L: Consider liver biopsy to assess for cirrhosis, as this predicts hepatic fibrosis 4
• Any ferritin level with end-organ damage: Proceed to regular phlebotomy with same endpoints 1

Maintenance Phase Protocol

Continue phlebotomy lifelong at individualized intervals (typically every 2-6 months) to maintain ferritin between 50-100 μg/L. 1, 2

Maintenance Monitoring

• Check hemoglobin before each maintenance phlebotomy 1, 3
• Monitor ferritin and transferrin saturation every 6 months 1, 4
• Adjust phlebotomy frequency based on ferritin trends 2

Blood Donation Eligibility

Blood removed during therapeutic phlebotomy can be used for transfusion in patients with uncomplicated hemochromatosis without significant organ damage during the maintenance phase, as deemed safe by the American Red Cross and FDA. 1

Dietary and Lifestyle Modifications

Absolute Contraindications

• Avoid vitamin C supplements entirely, especially during active iron depletion, as vitamin C accelerates iron mobilization and increases oxidative stress 1, 2, 3
• Avoid iron supplements 1
• Avoid raw or undercooked seafood due to Vibrio vulnificus infection risk 1
• Avoid contact of wounds with seawater 1

Dietary Recommendations

• No specific dietary iron restrictions are necessary, as dietary modification removes only 2-4 mg/day compared to 250 mg/week with phlebotomy 1
• Avoid daily red meat consumption 1
• Avoid moderate to heavy alcohol intake; patients with advanced liver disease should abstain completely 1

Alternatives When Phlebotomy is Contraindicated

Erythrocytapheresis

Erythrocytapheresis is the preferred alternative when phlebotomy is not tolerated, offering fewer hemodynamic changes and returning valuable blood components. 1

• Removes up to 1000 mL of red blood cells per session (versus 250 mL with phlebotomy) 5
• Reduces treatment duration by approximately 70% in the induction phase 5
• Mild citrate reactions are common but manageable 1
• Same ferritin targets apply: 50 μg/L for induction, 50-100 μg/L for maintenance 1

Iron Chelation Therapy

Use chelation only after careful risk-benefit assessment when neither phlebotomy nor erythrocytapheresis is possible. 1

• Deferoxamine 20-40 mg/kg/day subcutaneously is the traditional option 1, 2
  • Administered by continuous subcutaneous infusion 8-12 hours nightly for 5-7 nights weekly 1
  • Maximum urinary iron excretion achieved at approximately 2 g per 24 hours 1
• Deferasirox (Exjade) is an oral alternative, though concerns about adverse events have tempered enthusiasm for use in hemochromatosis 1, 6
• Chelation is first-line for secondary iron overload from ineffective erythropoiesis (e.g., thalassemia), not hereditary hemochromatosis 1, 3

Critical Pitfalls to Avoid

Cardiac Patients

In patients with cardiomyopathy or arrhythmias, rapid iron mobilization increases risk of sudden death due to toxic low-molecular-weight iron chelate pools. 1, 2, 3 Consider slower phlebotomy schedules or iron chelation instead.

Over-Treatment

Monitor closely to prevent iron deficiency, which can develop from excessive maintenance phlebotomy and persist for months with significant symptoms. 7 Development of iron deficiency or unexplained reduction in phlebotomy need warrants complete workup for alternative causes. 1

Compliance Issues

Approximately one-third of patients tolerate weekly phlebotomy, and compliance with maintenance therapy declines at a rate of 6.8% annually. 8 Anticipate adherence challenges and adjust schedules accordingly.