Therapeutic Phlebotomy Guidelines for Iron‑Overload Disorders

Indications

Therapeutic phlebotomy is recommended for hereditary hemochromatosis with iron overload, polycythemia vera, porphyria cutanea tarda, secondary iron overload from chronic transfusions, sickle‑cell disease, and non‑alcoholic fatty liver disease with hyperferritinemia. 1

All patients with confirmed hereditary hemochromatosis and serum ferritin above the normal range should start phlebotomy, irrespective of symptom presence. 2
Patients who already have end‑organ damage (e.g., liver disease, cardiomyopathy, arthropathy, diabetes, hypogonadism) must begin phlebotomy immediately, regardless of ferritin level. 3

Remove approximately 500 mL of whole blood weekly or bi‑weekly until serum ferritin falls to the target range of 50–100 µg/L. 3
Each unit of blood removed eliminates roughly 200–250 mg of iron. 3
Prior to every phlebotomy session, check hemoglobin/hematocrit and ensure the decline does not exceed 20 % from baseline. 3
Monitor ferritin after every 10–12 phlebotomies (≈ 3 months) during the early phase, then increase monitoring frequency as the target ferritin range is approached. 3

Continue lifelong phlebotomy at individualized intervals (from monthly to 1–2 units per year) to keep serum ferritin within 50–100 µg/L. 3

In patients with cardiac arrhythmias or cardiomyopathy, rapid iron mobilization raises the risk of sudden death; use slower phlebotomy schedules or consider iron‑chelation therapy instead. 3
Do not supplement vitamin C during active iron depletion, as it accelerates iron release and can cause transferrin saturation and oxidative stress. [3][2]

Erythrocytapheresis is the preferred alternative when standard phlebotomy is not feasible; it removes up to 1 L of red cells per session (≈ 4 × the iron removed by phlebotomy) and shortens total treatment duration by ~70 % while achieving the same ferritin targets. 1
Iron chelation (deferoxamine 20–40 mg/kg/day subcutaneously or oral deferasirox) should be reserved as second‑line therapy only when neither phlebotomy nor erythrocytapheresis can be performed. Deferasirox is not approved for hereditary hemochromatosis by the European Medicines Agency and should be avoided in advanced liver disease. 1

Delay of treatment while awaiting symptoms in confirmed hemochromatosis with elevated ferritin can lead to irreversible organ damage. 3
Over‑treatment: stop phlebotomy once ferritin reaches 50–100 µg/L to prevent iron‑deficiency anemia, which may cause significant symptoms for months. [3][2]
Relying on dietary iron restriction as primary therapy is ineffective; diet reduces iron intake by only 2–4 mg/day versus 200–250 mg/week removed by phlebotomy. 3
Prescribing iron supplements or iron‑fortified foods is contraindicated in iron‑overload states. 1
Advise patients to avoid raw or undercooked shellfish, which pose a risk of Vibrio vulnificus infection in the setting of iron overload. 1