Initiation of Hemochromatosis Treatment

Indications for Treatment Based on Biological Markers

The American Association for the Study of Liver Diseases recommends that patients with hemochromatosis and serum ferritin levels ≥300 μg/L in men or ≥200 μg/L in women should initiate phlebotomy treatment, regardless of the presence or absence of symptoms 1, 2
Patients who are homozygous for the C282Y mutation in the HFE gene with provisional iron overload (transferrin saturation >45% and ferritin >200 μg/L in women or saturation >50% and ferritin >300 μg/L in men and postmenopausal women) should start treatment 2
Patients with elevated ferritin levels (<1000 μg/L) without significant liver disease (elevation of ALT, AST) can proceed directly to phlebotomy without liver biopsy 1, 4

The decision to treat hemochromatosis with phlebotomy is straightforward and easy to justify for patients with signs of liver disease or other organ damage 4, 5
For asymptomatic patients (e.g., homozygous C282Y with ferritin of 800 μg/L, normal liver tests, and no symptoms), preventive treatment is recommended because it is easy, safe, and inexpensive and can prevent complications 4, 5
Early treatment before the development of cirrhosis and/or diabetes significantly reduces morbidity and mortality associated with hemochromatosis 6

Certain clinical manifestations are likely to improve with phlebotomy, including malaise and fatigue, skin pigmentation, insulin requirements for diabetics, and abdominal pain 6
Other manifestations respond less well or not at all to treatment, including arthropathy, hypogonadism, and advanced cirrhosis 6

Induction phase: weekly or biweekly phlebotomy (removal of 450-500 mL of blood) until serum ferritin reaches 50 μg/L 1, 2
Check hematocrit/hemoglobin before each phlebotomy and do not allow a drop of more than 20% from the previous value 1, 2
Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months) during the initial phases of treatment 7
Maintenance phase: maintain serum ferritin between 50 and 100 μg/L with periodic phlebotomies 1, 2

Avoid vitamin C and iron supplements during treatment 1, 2
Patients with advanced cardiac disease (arrhythmias or cardiomyopathy) are at increased risk of sudden death with rapid iron mobilization 4
Cirrhotic patients should continue to be screened for hepatocellular carcinoma after phlebotomy, as this risk persists despite treatment 6

Erythrocytapheresis may be considered as a therapeutic option based on availability, local expertise, and patient needs and preferences 2
Iron-chelating medications are reserved as second-line treatment in selected cases after careful evaluation of the risk-benefit ratio 2