The therapy of hemochromatosis involves removal of the excess body iron and supportive treatment of damaged organs. Iron removal is best accomplished by weekly or twice-weekly phlebotomy of 500 mL. Although there is an initial modest decline in the volume of packed red blood cells to about 35 mL/dL, the level stabilizes after several weeks. The plasma transferrin saturation remains increased until the available iron stores are depleted. In contrast, the plasma ferritin concentration falls progressively, reflecting the gradual decrease in body-iron stores. One 500-mL unit of blood contains 200–250 mg of iron, and ≥25 g of iron may have to be removed. Therefore, in patients with advanced disease, weekly phlebotomy may be required for 1–2 years, and it should be continued until the serum ferritin level is ≤100 μg/L. Thereafter, phlebotomies are performed at appropriate intervals to maintain ferritin levels at ≤100 μg/L. The transferrin saturation fluctuates and may still be elevated but should not dictate further therapy unless it is persistently at 100% when free unbound iron may circulate. Usually one phlebotomy every 3 months will suffice. It is important, however, not to overtreat and render the patient iron-deficient.
Chelating agents such as deferoxamine, when given parenterally, remove 10–20 mg of iron per day, which is much less than that mobilized by once-weekly phlebotomy. Phlebotomy is also less expensive, more convenient, and safer for most patients. However, chelating agents are indicated when anemia or hypoproteinemia is severe enough to preclude phlebotomy. Subcutaneous infusion of deferoxamine using a portable pump is the most effective means of its administration.
An effective oral iron chelating agent, deferasirox (Exjade), is now available. This agent is effective in thalassemia and secondary iron overload, but it is expensive and carries the risk of significant side effects.
Alcohol consumption should be severely curtailed or eliminated because it increases the risk of cirrhosis in hereditary hemochromatosis nearly tenfold. Dietary adjustments are unnecessary, although vitamin C and iron supplements should be avoided. The management of hepatic failure, cardiac failure, and diabetes mellitus is similar to conventional therapy for these conditions. Loss of libido and change in secondary sex characteristics are managed with testosterone replacement or gonadotropin therapy (Chap. 384).
End-stage liver disease may be an indication for liver transplantation, although results are improved if the excess iron can be removed beforehand. The available evidence indicates that the fundamental metabolic abnormality in hemochromatosis is reversed by successful liver transplantation.