PHARMACOLOGICAL TREATMENT

• The recommended treatment for most patients is therapeutic phlebotomy [206]
• Therapeutic phlebotomy includes an induction phase to induce iron depletion and a maintenance phase to prevent excess iron reaccumulation.
• Therapeutic phlebotomy can be performed safely in the physician's office or even in the patient's home. Therapy should not be delayed until symptoms develop, as the goal of therapy is to prevent irreversible organ damage [206, 207]
• Care must be taken to assure optimal pre- and post-phlebotomy hydration [206]
• Precautions to avoid postphlebotomy orthostatic hypotension should be observed after each treatment.
• Adequate dietary protein, vitamin B12, and folate intake should be encouraged to support the accelerated erythropoiesis that occurs with therapy.
• For patients who find venipuncture uncomfortable, comfort can be enhanced by prescribing a topical anesthetic preparation for use before each treatment.
• Erythropoietin therapy can be used for patients with iron overload and hypoproliferative anemias, such as in renal disease and anemia of chronic disease. In such cases with complicating hematopoietic disease, balancing therapies can be difficult, and appropriate consultation is suggested [206].
• Iron chelation therapy is reserved for patients who are severely anemic[206, 207]
• Deferoxamine is generally well tolerated, but it has serious adverse side effects and is inconvenient and expensive.
• Oral agents are being investigated, but they are also associated with higher costs and undesirable side effects.
Induction Phase
• Effective initial treatment requires removal of 5 to 20 g of iron for most patients [209]
• Each unit of whole blood (500 mL) contains approximately 250 mg of iron [206,207]
• The frequency of phlebotomy depends on the severity of iron overload symptoms as well as the patient's overall state of health.
• For patients with average or better body mass and evidence of ongoing iron toxicity, aggressive treatment with twice weekly phlebotomy is indicated and generally well tolerated [206]
• For those patients with iron overload and little or no evidence of toxicity, a less aggressive schedule of weekly or biweekly phlebotomy is sufficient.
• Erythroid hyperplasia occurs after a few weeks of treatment, which can permit acceleration of the treatment schedule in some patients [206]
• In general, because of sex differences and the effects of time on the extent of iron accumulation, men require more phlebotomies than women, and older patients require more treatments than younger patients.
• During the induction phase, most authorities recommend that the hematocrit be measured before every other phlebotomy.
• For patients on a less aggressive treatment schedule, the hematocrit can be measured before every third or fourth treatment as long as the patient is asymptomatic.
• The target hematocrit during therapy is 35% to 40%.
• The serum ferritin level is the most reliable and least expensive measure of the response to treatment.
• Serum ferritin should generally be measured after each month of treatment until it falls below 100 µmg/L. Thereafter, it should be measured after every other treatment.
• Iron depletion occurs when serum ferritin decreases to 20 to 50 µmg/L or when the hematocrit fails to rise above 33% for more than 3 weeks after treatment [206]
Maintenance Phase
• After completion of the induction phase, maintenance therapy is required indefinitely to maintain normal iron stores.
• This phase usually requires two to four phlebotomy sessions each year with a goal of maintaining the serum ferritin level at less than 50 µmg/L.
Response to Therapy
• Although the end points for the treating physician are easily measurable, the responses perceived by the patient might not be so evident. Most patients report improvements in strength and pigmentation.
• Cardiomyopathy, if not severe, is likely to improve through the process of remodeling once the tissue toxin is removed.
• Hyperglycemia often improves with treatment.
• Liver congestion and liver enzymes are likely to improve.
• Unfortunately, the arthritic symptoms, hypogonadism, and hypothyroidism do not improve with treatment.
• The endocrinopathies and arthritis caused by hereditary hemochromatosis might even continue to worsen despite treatment.
• Cirrhosis, if present, is not likely to improve,although treatment might result in slowing the progression of cirrhosis in a few affected patients.
• The most dreaded outcome of hereditary hemochromatosis in patients with evidence of cirrhosis is developing hepatocellular carcinoma
SECONDARY IRON OVERLOAD

• Treatment of secondary iron overload should be tailored to the underlying cause. Phlebotomy using a regimen similar to HH may be tolerated in some forms of secondary iron overload without preexisting anemia.
• Parenteral chelation therapy with deferoxamine is currently the treatment of choice in patients with chronic dyserythropoietic syndromes or chronic hemolytic anemia.
• Monitoring of the efficacy of therapy during chelation may require repeat liver biopsies to confirm adequate reduction of HIC

FOLLOW UP
• In men and postmenopausal women, transferrin saturations of 45% to 54% should be monitored at 1- to 2-year intervals [200]
• In patients with an elevated transferrin saturation but normal serum ferritin levels and normal liver enzyme levels, it is prudent to monitor these values yearly [200]
• Serum ferritin should generally be measured after each month of treatment until it falls below 100 µmg/L. Thereafter, it should be measured after every other treatment [200]