| PCT |
1a. Phlebotomy is the preferred treatment in patients with iron overload or hemochromatosis gene mutations. 400-500 mL of blood is removed either once per week until serum ferritin is <25 ng/mL. Rule of thumb for number of unit that will need to be removed: Each unit of blood (500 mL) removed will lead to decrease in SF = 30 ng/mL. Thus, if pre-phlebotomy SF = 600 ng/ml, 19 units will need to be removed in order for serum ferritin to decrease to ~25 ng/mL. If there are no chronic viral infections (e.g., HBV, HCV, HIV), the blood removed can be used by blood centers. Typically, continue weekly or biweekly phlebotomy as long as pre-phlebotomy Hgb/Hct >11 g/dL/33%. The goal of therapy is NOT to produce anemia nor to decrease serum transferrin saturation into a sub-normal range, but to deplete total body iron stores gradually, as reflected by SF. Some persons with HHC (e.g., C282Y+/+) increase gut iron absorption markedly in response to phlebotomy and thus serum transferrin saturations may be increased (55-80%). To decrease these values would require excessive iron removal and iron deficiency anemia, which is not necessary or advisable. 1b. Iron chelation: If subjects have underlying anemia or poor venous access, oral or parenteral iron chelation may be considered. In the USA, Deferasirox (Exjade, Novartis) is available. In Canada, Deferiprone is also available. The usual dose of Deferasirox is 10 mg/Kg BW/day. This therapy is much more expensive and has potential adverse effects (e.g., skin rash, nephrotoxicity, hepatotoxicity, especially as total body iron levels fall). Thus, regular monitoring of serum BUN, creatinine, ALT, AST, alkaline phosphatase, and bilirubin are necessary. Parenteral iron chelation with Deferoxamine (Desferal, Novartis) may also be considered. However, it must be administered nightly by SQ infusion with a pump; it is expensive and it too has potential adverse effects (e.g., auditory [CN 8] toxicity and development of cataracts. 2. Diet: Avoid iron supplements, vitamins or other supplements that include iron. Decrease intake of liver, steaks, chops, other red meats (heme iron is especially well-absorbed). Drink tea (green or black) with meals; tea decreases iron absorption from the gut. -
3. Antimalarials:
Chloroquine may be added to phlebotomy regimen to accelerate treatment response. Alternatively, it may be used when phlebotomy is contraindicated due to presence of anemia. It is dosed at 125 mg twice a week. Clinical effect is generally seen within ~6 months. Therapy should continue until full biochemical remission, often a year or more. Hydroxychloroquine 200 mg twice weekly.
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4. If with advanced end-stage renal disease (options):
Mobilization of iron stores via erythropoietin combined with small phlebotomies (50-100 mL) is preferred. Use of dialyzers with ultra-permeable membranes with blood flow rates higher than routine may reduce plasma porphyrins Plasmapheresis should be considered in severe cases. Renal transplantation is curative in severe cases refractory to above modalities in PCT associated with renal failure.
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Urinary or plasma porphyrins may be followed every 2-3 months. Porphyrin levels typically become normal as the target ferritin is approached. |
