Robert B. Hash, MD, Department of Family Medicine, Mercer University School of Medicine, Macon, Ga 

J Am Board Fam Med. 2001;14(4) 

In This Article

Treatment

The recommended treatment for most patients is therapeutic phlebotomy.[9] Therapeutic phlebotomy includes an induction phase to induce iron depletion and a maintenance phase (see below) to prevent excess iron reaccumulation. Therapeutic phlebotomy can be performed safely in the physician's office or even in the patient's home.[9] Therapy should not be delayed until symptoms develop, as the goal of therapy is to prevent irreversible organ damage.[9,26]

Care must be taken to assure optimal pre- and post-phlebotomy hydration.[9] 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.

Patients should be counseled to maintain a diet with only moderate amounts of high-iron-content foods.[9] Iron supplementation in any form should be strictly avoided. There is no reason to discourage vitamin C intake, with the exception of limiting those patients who choose to take supplements to 500 mg/d.[9,26] Ethanol should be avoided completely in patients with liver disease.[43]

Patients should be advised to avoid uncooked seafood, because they have a unique susceptibility to Vibrio vulnificus infection. Similarly, these patients are at increased risk of infection with this organism if they expose open wounds to warm coastal seawater. Therapeutic phlebotomy treatment does not reduce susceptibility to V vulnificus infection.[9]

Erythropoietin therapy can be used for patients with iron overload and hypoproliferative anemias, such as in renal disease and anemia of chronic disease.[9] In such cases with complicating hematopoietic disease, balancing therapies can be difficult, and appropriate consultation is suggested.

Iron chelation therapy is reserved for patients who are severely anemic.[9,26] Deferoxamine is generally well tolerated, but it has serious adverse side effects and is inconvenient and expensive.[2,26] Oral agents are being investigated, but they are also associated with higher costs and undesirable side effects.[2]

Effective initial treatment requires removal of 5 to 20 g of iron for most patients.[18] Each unit of whole blood (500 mL) contains approximately 250 mg of iron.[9,26] 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.[9] 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.[9,29] 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.[2] The target hematocrit during therapy is 35% to 40%.[29]

The serum ferritin level is the most reliable and least expensive measure of the response to treatment.[9] 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.[9] 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.[8,9,26,29]

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[9] with a goal of maintaining the serum ferritin level at less than 50 µmg/L.[26]

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.[9] The endocrinopathies and arthritis caused by hereditary hemochromatosis might even continue to worsen despite treatment.[7] Cirrhosis, if present, is not likely to improve,[29] although treatment might result in slowing the progression of cirrhosis in a few affected patients.[9] Cirrhosis is the most reliable predictor of survival. If there is no cirrhosis at the time of diagnosis, patients have a normal survival with treatment. If cirrhosis is present, 5- and 10-year survivals with treatment are 72% and 62%, respectively.[29]

The most dreaded outcome of hereditary hemochromatosis in patients with evidence of cirrhosis is developing hepatocellular carcinoma.[37] The risk of developing this cancer is as high as 19% if cirrhosis is present, and 5% if cirrhosis is not present.[20] Many authorities recommend monitoring the fetoprotein level or scheduling a hepatic sonogram every 6 months for patients with cirrhosis, but effectiveness of this strategy is unclear.[9,26,29]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....