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Health Protocols


Conventional Treatment

Phlebotomy The standard treatment for patients with iron overload is bloodletting (phlebotomy or venesection) in the absence of anemia and chelation in the iron-loading anemias (Fleming 2012; Pietrangelo 2010). One unit (about 450 ml) of blood contains approximately 200-250 mg of iron, depending upon the hemoglobin concentration; it is often recommended to remove one unit per week (as tolerated). In patients who have very high total body iron stores greater than 30 g, therapeutic phlebotomy (i.e., removal of blood) may take up to 1-2 years to adequately reduce iron stores, until serum ferritin levels and transferrin saturation values fall within normal ranges. Ferritin levels are then typically maintained by removal of 2-4 units of blood per year (Pietrangelo 2010).

A potential drawback of phlebotomy is a decrease in hepcidin levels and excess iron absorption (Fleming 2012). Removal of blood initiates the compensatory synthesis of new red blood cells in bone marrow. These new red blood cells have increased iron requirements through enhanced production of the oxygen-carrying protein hemoglobin. Thus, hepcidin levels may be further decreased so additional iron can be absorbed to meet increased demand (van Dijk 2008).

In one study among patients with hereditary hemochromatosis, phlebotomy was associated with decreased hepcidin levels; although subjects’ hepcidin levels were low initially (van Dijk 2008; Galesloot 2011). Targeting a serum ferritin level slightly above the recommended range during maintenance phlebotomy may help some patients avoid increased iron absorption caused by low hepcidin levels (van Dijk 2008).

Iron Chelation For patients refractory to phlebotomy treatment, or for those in which blood removal is not feasible (e.g., iron-loading anemia patients), iron chelation is the standard therapy.

Currently, there are three FDA approved iron chelating agents. Desferoxamine mesylate (Desferal®) is an injectable iron chelator that has been in use since the 1960’s. It can bind and remove iron from ferritin stores or abnormal tissue deposits, but not from sites of active metabolic iron usage (such as transferrin or hemoglobin). Desferoxamine has some considerable drawbacks; it can elicit hypersensitivity and systemic allergic reactions, and its short half-life requires treatment via a slow injection over a period of 4-12 hours (Heli 2011).

The development of oral iron chelators has enabled more convenient dosing and improved patient compliance. Deferiprone (Ferriprox®) is a synthetic analog of mimosine (a naturally occurring iron chelating compound, originally derived from the Mimosa pudica plant) (Hider 2005; Heli 2011). Its rapid metabolism by the liver requires that it be taken in high doses for efficacy. Side effects of deferiprone include gastrointestinal discomfort and skin rash. Deferasirox (Exjade®), an orally bioavailable chelator with a longer half-life and smaller effective dose than deferiprone, has been approved in the United States for treatment of secondary iron overload due to ineffective erythropoiesis since 2005. It exhibits some of the same side effects as deferiprone, with the possibility of more serious side effects (e.g., liver failure and renal dysfunction). It is also very expensive. Due to its small molecular size (compared to desferoxamine), deferasirox is able to move throughout the body, removing iron from the active sites of several critical iron-containing enzymes (Hider 1995; Heli 2011).