Workshop on Maintaining Iron Balance in Women
Blood Donors of Child-Bearing Age

Staff Contact/Phone
Dr. George Nemo, (301) 435-0075 (nemog@nih.gov)
Dr. Liana Harvath, (301) 435-0075 (harvath@nhlbi.nih.gov)
Dr. Barbara Alving, (301) 435-0080 (alvingb@nih.gov)

Purpose/Objective
To discuss the medical, economic and operational feasibility of implementing a program of carbonyl iron replacement to prevent iron deficiency in women blood donors of child-bearing age.

Workshop Speakers/Panel Members
Workshop speakers and panel members consisted of physicians with expertise in hematology, oncology, transfusion medicine, and blood center management, as well as representatives from the major blood banking organizations and patient/public advocacy groups. They were: Randy Alexander, Iron Disorders Institute; Cheryl Aylesworth, M.D., Uniformed Services University of the Health Sciences; Celso Bianco, M.D., America's Blood Centers; Gary Brittenham, M.D., College of Physicians and Surgeons, Columbia University; Linda Chambers, M.D., National Headquarters American Red Cross; Richard B. Counts, M.D., Puget Sound Blood Center; Roberta Crawford, Iron Overload Diseases Association; Ronald O. Gilcher, M.D., Oklahoma Blood Institute; Victor R. Gordeuk, M.D., Center for Sickle Cell Disease, Howard University; Paul Holland, M.D., Sacramento Blood Center; James P. Kushner, M.D., University of Utah Medical Center; Jay Menitove, M.D., Community Blood Center of Greater Kansas; and Merlyn Sayers, M.D., Ph.D., Carter Blood Care.

Meeting Agenda

Summary
Data were presented on the scope of the problem of blood donor deferrals due to low hemoglobin levels. There was agreement that many women blood donors are borderline in terms of iron stores. Approximately 5% of donors, 95% of whom are women, are deferred because of hemoglobin levels below 12.5 g/dL. Phlebotomy-induced iron deficiency is a significant problem resulting in significant loss of donations, many of which come from the most motivated, repeat donors. This problem affects special donors, such as O negative donors, disproportionately. Phlebotomy of a unit of blood produces a loss of 200 to 250 mg of iron in hemoglobin. Because the average amount of storage iron in a woman of child-bearing age is only about 300 mg, donation of a unit of blood requires the subsequent mobilization of much or all of this reserve. Further donations of blood will produce iron deficiency and then anemia. In women who donate blood repeatedly, iron absorption from a usual diet can not increase sufficiently to replace iron losses from frequent phlebotomy. One option to prevent development of iron deficiency would be to lengthen the donation interval for women to every 6-12 months, for example, or use a standard 56 day interval only if they receive iron replacement.

In a study supported by the National Heart, Lung, and Blood Institute, extramural investigators demonstrated the safety and efficacy of short-term carbonyl iron administration to frequent, committed female blood donors. The study showed that carbonyl iron supplements are an efficacious means for increasing blood donation in women of childbearing age. The results provide a scientific and practical basis for the consideration of short-term carbonyl iron replacement for menstruating women donors who wish to be donors as frequently as four times each year. This approach is becoming increasingly attractive as additional donor deferral criteria are put in place to protect the safety of the blood supply. Nevertheless, the workshop participants questioned the practicality of supplementing the diet of regular female donors under the age of 45 with iron so that they can continue to donate. It is clear that replacement of the iron that has been lost can be done. But there are many practical issues that need to be addressed when trying to apply what has been learned in small research studies to large groups of donors. What will be the cost of iron replacement per donor? Could a donor recruitment program be as cost effective with less risk? How is the success or failure of the program to be measured? There was general agreement that any programs evaluating iron replacement would need to be performed as research investigations at this time, since experience in this area has not yet risen to the level of standard practice.

Information for donors should be tailor-made to permit good understanding of the risks of iron deficiency and the interventions that are recommended to prevent it. Many female donors already take iron supplements and have increased iron in their diets. All participants agreed that carbonyl iron should be used, whether provided to the donor by the blood center or recommended to the donor as the type of supplement to buy, in order to reduce the likelihood of toxicity in case of accidental ingestion by children in the donor's household. Carbonyl iron is absorbed slowly from the GI tract and therefore has greatly reduced toxicity if accidentally ingested in large doses. The most common side effect of daily doses of carbonyl iron (mild GI discomfort) is similar in frequency to ferrous sulfate/gluconate. Possible disadvantages of iron replacement programs include limited compliance due to side effects, the possibility of masking underlying diseases associated with blood loss, and the risk of giving iron to individuals with undiagnosed hereditary hemochromatosis.

What harm can be done?
The largest group of deferred donors are menstruating women who, even with hemochromatosis, are unlikely to have iron overload and organ damage. Hemochromatosis screening was discussed. One blood center is in the process of initiating screening for the HFE gene (a genetic determinant of hemochromatosis). The cost of the test is modest (may be as low as $5.00 under special circumstances) and only has to be performed once. However, there were concerns expressed that genetic screening carries with it the potential for discrimination of those found to have the atypical gene(s) with regard to employment, or health or life insurance.

Another risk of iron replacement may be delayed diagnosis of such disorders as GI neoplasms, other neoplasms associated with blood loss, or peptic ulcer disease. However, these conditions occur rarely in the group between 18 and 45 years of age. It was recommended that a supplemental questionnaire be designed that would identify donors at higher risk of having non-iron deficiency causes of anemia, asking such questions as "Does anyone in your family have colon cancer?", "Do you take medications for heartburn or ulcers?", and "Do you have ulcerative colitis or Crohn's disease?"

It is estimated that iron supplementation would increase the number of units available for transfusion by about a half million per year. This was considered to be a significant number by the workshop participants.

The approach of supplementing early in the donation process in order to prevent iron deficiency, rather than treating phlebotomy-induced iron deficiency, was better accepted by the participants. Most thought that, at some point in any protocol of iron replacement, a more complete evaluation of iron status (e.g., ferritin, transferrin iron saturation, etc.) should be undertaken to evaluate the effects of replacement and to eliminate any participants who are asymptomatic.

The patient/public advocate participants were supportive of broader use of iron studies to evaluate donors, and indicated a willingness to be involved in subsequent studies and discussions on the matter of iron supplementation in blood donors.

The point was made that the cost of a donor recruitment program to replace lost donors due to iron deficiency may be less than the cost of a research iron replacement program. An iron replacement program may well require special nurse coordinators. It may also be necessary to continue special non-standard management of the supplemented donors in order to keep them involved. At one blood center in which women received iron replacement during a research study, a significant drop-out of donors occurred when the study was completed and the participants who had received iron replacement were moved into the routine program. It was stressed that a committed staff is needed for an iron replacement program to be successful. Furthermore, the staff needs to be educated fully about the program.

It was agreed that iron physiology in blood donors is well understood and that iron replacement works, at least in the controlled environment of a research program. It is the operational issues that still need to be resolved and evaluated. It was pointed out that usual methods for donor hemoglobin screening are both insensitive and nonspecific, so that an accurate identification of donors with hemoglobin below 12.5 g/dL would require use of more reliable sample types (e.g. venipuncture instead of fingerstick) and testing (e.g. automated counter instead of spun microhematocrit) methodologies. Participants also identified the need for donor input. Donors should be queried about how they feel about becoming iron deficient from donation. How do they respond to being deferred for having a hemoglobin value below 12.5 g/dL? Are they receptive to taking pills in support of voluntary donation? Will they comply?

Most participants thought that iron replacement should be offered, preferably in a research study, to special subgroups of donors such as those with blood types in great need (e.g., O negative) or who have rare blood types. Most believed that the operational barriers are too great to offer iron to all blood donors in need of replacement, or to forestall iron deficiency.

Recommendations:

• Consider implementing a demonstration and education research program of iron replacement in women blood donors of child-bearing age.
  
  
• The objective of the research program is to determine the operational feasibility of providing carbonyl iron replacement to these donors.
  
  
• The program should involve several blood centers.
  
  
• Studies of donor attitudes concerning an iron replacement program should be considered.