Phlebotomy
The
recommended treatment for most patients is therapeutic phlebotomy. 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.
Care must be
taken to assure optimal pre- and post-phlebotomy hydration.
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. 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. Ethanol should be avoided completely in patients with
liver disease.
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.
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.
Iron
chelation therapy is reserved for patients who are
severely anemic. 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.
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Induction
Phase
Effective initial treatment requires removal of 5
to 20 g of iron for most patients. Each unit of whole
blood (500 mL) contains approximately 250 mg of iron. 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. 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. 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 µg/L. Thereafter, it should be measured after every other
treatment. Iron depletion occurs when serum ferritin decreases to 20
to 50 µg/L or when the hematocrit fails to rise above 33% for more
than 3 weeks after treatment.
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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 µg/L.
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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. 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.
The most dreaded outcome of
hereditary hemochromatosis in patients with evidence of cirrhosis is
developing hepatocellular carcinoma. The risk of
developing this cancer is as high as 19% if cirrhosis is present,
and 5% if cirrhosis is not present. Many authorities recommend
monitoring the |ga-fetoprotein level or scheduling a hepatic
sonogram every 6 months for patients with cirrhosis, but
effectiveness of this strategy is unclear.
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