The recent availability of a genetic test (homozygosity for the C282Y mutation in the HFE gene) for the diagnosis of hereditary hemochromatosis (HH) has focused renewed attention on this disorder and has resulted in the diagnosis being made in younger subjects with smaller iron burdens. However, phlebotomy therapy in HH remains hampered by lack of simple, physiologic laboratory monitoring guides. In addition, phlebotomy therapy has been perceived as wasteful because the blood obtained has not been not used for allogeneic transfusion although many HH subjects meet standards for allogeneic blood donation. Recent regulatory changes now allow increased flexibility in establishing policies for transfusion of blood obtained from HH subjects. In studies performed over the last 12 years, we have developed a simple, physiologically based phlebotomy guide as the basis for a protocol to utilize blood from appropriate hemochromatosis patients for allogeneic transfusion. Prospective studies in the DTM have shown that the red cell mean corpuscular volume (MCV), a physiologic, precisely measured indicator of erythopoietic iron availability, when measured in conjunction with the hemoglobin, provides all the information necessary to manage patients during induction as well as maintenance phlebotomy. Phlebotomy was started weekly and transitioned to less frequent intervals when the MCV decreased to 5 to 10 percent below baseline and the hemoglobin and MCV were decreasing n concert. During maintenance phlebotomy, the hemoglobin was targeted at greater than 13 g/dL and the MCV was kept at 5 to 10 percent below baseline (generally 85 to 90 (3). A stable, asymptomatic, iron-depleted state was obtained in all patients after a median of 38 phlebotomies and removal of 9.0 grams of iron. The MCV was stable for a prolonged period during induction therapy, and then decreased in a smooth, consistent manner, indicating the onset of iron-limited erythropoiesis. Transferrin saturation varied considerably during phlebotomy, but remained below 40 percent during stable MCV-targeted maintenance. Ferritin values were not useful to assess the pace of iron depletion or maintenance phlebotomy. The median stable maintenance interval was 7.5 (range 6 to 16) weeks, corresponding to an average daily iron removal of 35 to 67(g/kg. The data in this study indicate that the red cell MCV is a physiologic, inexpensive guide to phlebotomy therapy in patients with HH. In contrast to standard, more expensive measurements such as ferritin levels, the MCV accurately predicts iron depletion, prevents excessive rebound transferrin saturation and guides maintenance according to each patient?s individual iron absorption. The MCV-guided phlebotomy guideline, along with extended rheumatologic and hepatic evaluations, forms the core of a large, omnibus protocol being developed to optimally manage phlebotomy in hemochromatosis patients while utilizing blood from appropriate patients for allogeneic transfusion.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL002107-01
Application #
6414298
Study Section
(DTM)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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