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Figure. Participation in Blood Donor Survey
Image description not available.
Eligible whole blood (community or directed) or apheresis donors had to be aged 18 years or older. All screening test results were available or at least 1 of the available test results was positive.
Table 1. Deferral Criteria of Blood Centers Participating in the 1998 Retrovirus Epidemiology Donor Study Survey
Image description not available.
Table 2. Demographic Characteristics and Donation Practices by Donor Health Status
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Table 3. Unweighted Proportions of Unreported Deferrable Risks and Positive Screening Test Results by Donor Health Status
Image description not available.
1.
Bothwell TH, MacPhail AP. Hereditary hemochromatosis: etiologic, pathologic, and clinical aspects.  Semin Hematol.1998;35:55-71.
2.
Walker EM, Wolfe MD, Norton ML. Hereditary hemochromatosis.  Ann Clin Lab Sci.1998;28:300-312.
3.
Edwards CQ, Kushner JP. Screening for hemochromatosis.  N Engl J Med.1993;328:1616-1620.
4.
Leggett BA, Halliday JW, Brown NN. Prevalence of haemochromatosis amongst asymptomatic Australians.  Br J Haematol.1990;74:525-530.
5.
McLaren Not Available, Gordeuk VR, Looker AC.  et al.  Prevalence of heterozygotes for hemochromatosis in the white population of the United States.  Blood.1995;86:2021-2027.
6.
Edwards CQ, Griffen LM, Goldgar D.  et al.  Prevalence of hemochromatosis among 11,065 presumably healthy blood donors.  N Engl J Med.1988;318:1355-1362.
7.
Witte DL, Crosby WH, Edwards CQ.  et al.  Practice guideline development task force of the College of American Pathologists: hereditary hemochromatosis.  Clin Chim Acta.1996;245:139-200.
8.
Barton JC, McDonnell SM, Adams PC.  et al.  Management of hemochromatosis.  Ann Intern Med.1998;129:932-939.
9.
Niederau C, Rudolf F, Purschel A. Long-term survival in patients with hereditary hemochromatosis.  Gastroenterology.1996;110:1107-1119.
10.
Powell LW. Hemochromatosis: the impact of early diagnosis and therapy [editorial].  Gastroenterology.1996;110:1304-1307.
11.
Jeffrey G, Adams PC. Blood from patients with hereditary hemochromatosis—a wasted resource?  Transfusion.1999;39:549-550.
12.
Levstik M, Adams PC. Eligibility and exclusion of hemochromatosis patients as voluntary blood donors.  Can J Gastroenterol.1998;12:61-63.
13.
Tan L, Khan MK, Hawk JC.for the Council on Scientific Affairs, American Medical Association.  Use of blood therapeutically drawn from hemochromatosis patients.  Transfusion.1999;39:1018-1026.
14.
Grindon AJ. Blood donation from patients with hemochromatosis.  JAMA.1993;270:880.
15.
Conry-Cantilena C, Klein HG. Hemochromatosis patients as blood and tissue donors. In: Edwards CQ, Barton JC, eds. Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment. Cambridge, England: Cambridge University Press; 2000:564-573.
16.
Cherubin CE, Prince AM. Serum hepatitis specific antigen (SH) in commercial and volunteer sources of blood.  Transfusion.1971;11:25-27.
17.
Szmuness W, Prince AM, Brotman B, Hirsch RL. Hepatitis B antigen and antibody in blood donors: an epidemiologic study.  J Infect Dis.1973;127:17-25.
18.
Alter HJ, Holland PV, Purcell RH.  et al.  Posttransfusion hepatitis after exclusion of commercial and hepatitis-B antigen-positive donors.  Ann Intern Med.1972;77:691-699.
19.
Aach RD, Kahn RA. Post-transfusion hepatitis: current perspectives.  Ann Intern Med.1980;92:539-546.
20.
Domen RE. Paid-versus-volunteer blood donation in the United States: a historical review.  Transfus Med Rev.1995;9:53-59.
21.
Seeff LB. Transfusion-associated hepatitis B: past and present.  Transfus Med Rev.1988;2:204-214.
22.
Munsterman KA, Grindon AJ, Sullivan MT.  et al.  Assessment of motivations for return donation among deferred blood donors.  Transfusion.1998;38:45-50.
23.
Eastlund T. Monetary blood donation incentives and the risk of transfusion-transmitted infection.  Transfusion.1998;38:874-882.
24.
Johnson ES, Doll GA, Satten B.  et al.  Direct oral questions to blood donors: the impact on screening for human immunodeficiency virus.  Transfusion.1994;34:769-774.
25.
Williams AE, Thomson RA, Schreiber GB.  et al.  Estimates of infectious disease risk factors in US blood donors.  JAMA.1997;277:967-972.
26.
Glynn SA, Kleinman SH, Schreiber GB.  et al.  Trends in incidence and prevalence of major transfusion-transmissible viral infections in US blood donors, 1991 to 1996.  JAMA.2000;284:229-235.
27.
McDonnell SM, Grindon AJ, Preston BL.  et al.  A survey of phlebotomy among persons with hemochromatosis.  Transfusion.1999;39:651-656.
28.
 Not Available  7 Federal Register.86 (2001) (codified at 21 CFR §640.3).
29.
Center for Biologics Evaluation and Research.  Guidance for Industry Variances for Blood Collection From Individuals With Hereditary Hemochromatosis (draft). Rockville, Md: Center for Biologics Evaluation and Research; December 2000. http://www.fda.gov/cber/gdlns/hemchrom.htm. Accessibility verified September 5, 2001.
30.
Barton JC, Grindon AJ, Barton NH, Bertoli LF. Hemochromatosis probands as blood donors.  Transfusion.1999;39:549-550.
31.
Zuck TF, Thomson RA, Schreiber GB.  et al.  The Retrovirus Epidemiology Donor Study (REDS): rationale and methods.  Transfusion.1995;35:944-951.
32.
 WESVAR SAS Procedures . Rockville, Md: Westat, Inc; August 1994.
33.
Thomas DG. Exact confidence limits for an odds ratio in a 2 × 2 table.  Appl Stat.1971;20:105-110.
34.
 StatXact4 [software program]. Cambridge, Mass: Cytel Software Co; 1999.
35.
Mitka M. Blood groups differ on donor deferral.  JAMA.2001;285:1694-1695.
36.
 Routine screening for iron overload/hemochromatosis. In: Proceedings of the 146th Annual Meeting of the House of Delegates of the American Medical Association; June 22-26, 1997; Chicago, Ill. Resolution 525.
37.
Sacher RA. Hemochromatosis and blood donors: a perspective [commentary].  Transfusion.1999;39:551-554.
38.
Cumming PD, Wallace EL, Schorr JB, Dodd RY. Exposure of patients to human immunodeficiency virus through the transfusion of blood components that test antibody-negative.  N Engl J Med.1989;321:941-946.
39.
Piliavin JA. Why do they give the gift of life? a review of research on blood donors since 1977.  Transfusion.1990;30:444-459.
40.
Busch MP, Kleinman SH. Nucleic acid amplification testing of blood donors for transfusion-transmitted infectious diseases: report of the Inter-organizational Task Force on Nucleic Acid Amplification Testing of Blood Donors.  Transfusion.2000;40:143-159.
Original Contribution
September 26, 2001

Prevalence, Donation Practices, and Risk Assessment of Blood Donors With Hemochromatosis

Author Affiliations

Author Affiliations: Westat (Drs Bethel, Schreiber, and Glynn and Ms Sanchez) and the Jerome H. Holland Laboratory, American Red Cross (Dr Williams), Rockville, Md; National Heart, Lung, and Blood Institute, Bethesda, Md (Dr McCurdy); and the Sylvan N. Goldman Center, Oklahoma Blood Institute, Oklahoma City (Dr Gilcher). Dr Williams is now with the US Food and Drug Administration, Rockville, Md.

JAMA. 2001;286(12):1475-1481. doi:10.1001/jama.286.12.1475
Context

Context Despite changes in eligibility policies, practical barriers limit blood donations from individuals with hemochromatosis. Increased knowledge of hemochromatosis donor characteristics may help foster further changes that will promote more donations.

Objectives To estimate the prevalence of donors diagnosed as having hemochromatosis and to compare rates of unreported deferrable risks for transfusion-transmissible viral infections (TTVIs), positive screening test results for TTVIs, and donation patterns between hemochromatosis patient donors and donors reporting no medical conditions necessitating phlebotomy (non–health-related donors).

Design An anonymous mail survey conducted in 1998 as part of the ongoing Retrovirus Epidemiology Donor Study.

Setting and Participants Among a stratified probability sample of 92 581 blood donors from 8 geographically diverse US blood centers, 52 650 (57%) responded.

Main Outcome Measures Prevalence of hemochromatosis among blood donors; prevalence of unreported deferrable risks and positive screening test results for TTVIs among hemochromatosis patient donors vs non–health-related donors.

Results One hundred ninety-seven respondents (0.4%) identified themselves as hemochromatosis patients and 50 079 (95.1%) as non–health-related donors. An estimated 0.8% of all donations were from hemochromatosis patients, 45.8% of whom reported that they had donated blood to treat their illness. The proportion of repeat donors was higher in hemochromatosis patients than in non–health-related donors (83.5% vs 76.5%; P = .03). Among repeat donors, 68.7% of hemochromatosis patients reported donating at least 3 times in the past year compared with 49.1% of non–health-related donors (P<.001). The prevalence of unreported deferrable risks for TTVIs was similar in hemochromatosis patients (2.0%) and non–health-related donors(3.1%) as was the overall prevalence of positive screening test results (1.3% of hemochromatosis patients vs 1.6% of non–health-related donors).

Conclusions Although significant numbers of hemochromatosis patients reported donating blood for therapeutic reasons, our findings suggest that this population does not present a greater risk to blood safety than other donors.

Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism characterized by an increase in iron absorption from the gastrointestinal tract, which can lead to the accumulation of iron in multiple organs and tissues.1,2 Although once believed to be rare, with current genetic advances, hemochromatosis is now widely recognized as a common condition.35 Among white people living in the United States, the prevalence is estimated at 0.5%.6 If untreated, hemochromatosis can result in the development of hepatic cirrhosis, hepatocellular carcinoma, cardiac failure, diabetes mellitus, arthritis, and premature death.1,2 Most clinical complications can be avoided if the disorder is identified early and is treated with periodic phlebotomies to facilitate iron unloading from critical organs.2,710 Management commonly includes the weekly or slightly less frequent removal of 1 to 2 units (450-1000 mL) of blood until iron stores are depleted, then maintenance phlebotomies to regulate iron stores. Men typically require 3 or 4 units and women 1 or 2 units to be removed annually.8

Although there is no known added risk to transfusion recipients of products from hemochromatosis donors,11,12 the US Food and Drug Administration (FDA) has required and the American Medical Association (AMA) has endorsed13 that blood collected from otherwise healthy hemochromatosis patients be used with some restrictions. The principal concern is the perceived benefits these patients may receive from donating.14,15 Early research suggests that blood from paid donors is more likely to transmit hepatitis than blood from altruistic volunteer donors.1619 This work led to the initiation of an all-volunteer donor system in the 1970s,20 a move that resulted in a significant decrease in the incidence of posttransfusion hepatitis.21 It has been hypothesized that certain incentives might induce some individuals with risk factors for transfusion-transmissible viral infections (TTVIs) to conceal their history to avoid being deferred.22,23 The deferral of individuals with risk factors is still the principal means of reducing the likelihood of collecting recently acquired infectious donations not detected by laboratory testing.24,25 The effectiveness of donor screening is suggested by the fact that the prevalence of all major TTVIs in first-time donors, a population that has not been prescreened by laboratory TTVI testing, are considerably lower than in the general population.26

While not receiving payment for donating, hemochromatosis patients may still have a financial incentive for giving. The mean cost of phlebotomy has been estimated at $74 per unit for those with partial or no insurance coverage,27 an expense that could be saved by donating. Because patients with hemochromatosis might benefit medically and financially from giving blood, there is concern that their blood may not be as safe as blood from volunteer donors.1315

Although the FDA does not prohibit the use of blood from hemochromatosis patients, it has required that all blood drawn during therapeutic phlebotomies be labeled specifying its source.28 Labeled blood can only be used at the discretion of physicians and their patients; in practice, labeled blood is not well accepted and is usually discarded.15 Food and Drug Administration policies further stipulate that a donor may not give more than 1 unit in 8 weeks without a physician's examination at the time of donation,28 a guideline that limits the potential for collecting blood during initial iron depletion therapy. The AMA advocates that therapeutic units from hemochromatosis patients be labeled until the potential financial inducement to donate can be removed.13

To permit the wider use of hemochromatotic blood, in 1999 the FDA began granting labeling and frequency of collection variances to blood collection organizations that offer no-cost phlebotomies to all patients with hemochromatosis. These variances enable blood to be collected from patients with hemochromatosis without labeling the unit, and if the patient presents a prescription for phlebotomy, a physician is not required to certify the patient's health regardless of when he/she last donated (J. E. Henney, MD, FDA memorandum [Blood Donations by Individuals With Hemochromatosis], August 10, 1999).29

Despite the reduced restrictions, there are still practical barriers limiting the use of hemochromatosis blood. Foremost, collection facilities must be willing to assume the costs associated with providing free therapeutic phlebotomies to those who do not qualify as blood donors. One study of 211 hemochromatosis probands found that 33% would not have met the criteria for blood donation.30 As of May 2001, 15 (10%) of 149 licensed and 3 (0.4%) of 853 registered-only blood collection organizations have applied for and received labeling and frequency of collection variances for hemochromatosis patients (A.E.W., written communication, May 29, 2001).

To realize the full benefit of collecting blood from patients with hemochromatosis requires a loosening of restrictions that can be accomplished only through increased understanding of the motivations, risk profiles, and donation behaviors of otherwise healthy patients with hemochromatosis. To our knowledge, this is the first large-scale study to address these questions.

METHODS

The findings reported are from an anonymous mail survey conducted in 1998 as part of the ongoing Retrovirus Epidemiology Donor Study (REDS), sponsored by the National Heart, Lung, and Blood Institute. REDS was designed to address US blood safety and availability concerns. Detailed descriptions of the REDS study have been published previously.31 A summary of the features that are relevant to the present inquiry are presented herein.

Participating centers included 8 large US blood centers: the American Red Cross (Greater Chesapeake and Potomac region, Southeastern Michigan region, and Southern California region); the Blood Centers of the Pacific-Irwin; the Oklahoma Blood Institute; Lifeblood, Mid-South Regional Blood Center; the New York Blood Center; and the Blood Bank of San Bernardino. At 7 centers, all individuals with diagnosed hemochromatosis were deferred. To eliminate any financial incentive for donating blood, 1 center offered therapeutic phlebotomies at no cost. This center permitted those with hemochromatosis to donate but only during periods when they did not require phlebotomy to treat their condition. Therefore, blood collected from patients who presented a prescription for therapeutic phlebotomy was never treated as a routine allogeneic blood donation; these units were labeled "for the treatment of hemochromatosis." Donors from this center were included in all analyses except for those of donors' reported discussions with health care professionals or the blood bank staff.

REDS collected laboratory test results and demographic data from all donations given at study centers. All data were entered into a central donation database maintained by the REDS coordinating center (Westat, Rockville, Md).

Survey Sample and Donor Classification

Monthly stratified probability samples were drawn from April through October 1998 from the population of study center donors aged 18 years or older who gave a whole blood (community or directed) or an apheresis donation for which either all screening test results were available or at least 1 of the available results was positive. The sample size for each blood center was between 8% and 18% of eligible donors depending on the number of donations the center collected. Young, first-time, and minority donors were oversampled due to higher rates of nonresponse in prior REDS surveys. All donors who screened positively for the antibody to hepatitis B core antigen or syphilis were sampled to generate data for a separate analysis of these outcomes. A total of 92 581 donors were surveyed (Figure 1).

Respondents were categorized based on their self-reported health status. Three groups were defined: donors who reported having hemochromatosis requiring therapeutic phlebotomy, donors who reported requiring phlebotomy for other health reasons (such as cardiovascular disease prevention), and donors who reported that phlebotomy had never been recommended as a means to improve their health (Figure 1). Our analyses were restricted to donors with hemochromatosis and those who did not have a health-related need for phlebotomy (non–health-related donors).

Survey Instrument

The questionnaire consisted of 71 multiple-choice questions and required approximately 20 minutes to complete. Participants were asked questions about their donation history, future donation plans, demographic characteristics, hemochromatosis status, and risk factors for TTVIs that should result in deferral if reported during donor screening (unreported deferrable risks) (Table 1). The surveys were encrypted prior to mailing with the following identifiers: donor status (first-time vs repeat donor), month and year of index donation, donation center, and overall screening test reactivity results. The survey instrument and procedures were approved by the institutional review boards of each blood center and by the US Office of Management and Budget.

Statistical Methods

Respondents were assigned a sampling weight to adjust for differential sampling and response rates. Prevalence estimates for most outcomes were based on weighted data and compared using weighted χ2 test analysis. The estimate of the proportion of donations from hemochromatosis donors was derived using the following formula: [(average number of donations per year reported by hemochromatosis donors) × (proportion of study donors with hemochromatosis) × (total number of allogeneic donors giving in 1998 at study blood centers)] / [(total number of allogeneic donations given in 1998 at study blood centers)]. Weighted data analyses were performed using WESVAR PC.32 The significance level was .05.

Because of the small sample of hemochromatosis donors, the low number of positive screening test results, and unreported deferrable risks, exact methods were used on unweighted data for the analyses of these outcomes. The association between a donor's health status and each of these outcomes was assessed by estimating odds ratios (ORs) and their 95% confidence intervals (CIs).33 The Fisher exact test was used to examine these associations when the data were stratified by first-time and repeat donor status. StatXact434 was used to perform all exact procedures.

Unweighted estimates of unreported deferrable risks and positive screening test results should not be interpreted as estimates of the population prevalence for these outcomes. As with other survey outcomes, these prevalence estimates need to be adjusted using sampling weights to correct for design and nonresponse effects. Weighting of the data was of particular importance when deriving positive screening test prevalence because donors who screened positively were oversampled.

RESULTS

Of the 92 581 donors surveyed, 52 650 (57%) returned questionnaires, and we identified 197 donors (0.4%) with hemochromatosis and 50 079 (95.1%) reporting no medical need for phlebotomy (Figure 1). Response rates were highest among donors who were white (69%), 45 years or older (67%), and who had given prior donations (repeat donors) (61%).

Compared with non–health-related donors, those with hemochromatosis were more likely to be white, 45 years or older, and men (Table 2). On average, those with hemochromatosis reported giving more donations per year than non–health-related donors (3 vs 2; P<.001). We estimated that 0.8% of all donations were from individuals with hemochromatosis. Forty-six percent of donors with hemochromatosis reported that their primary motivation for donating some or every time was to treat their illness.

As shown in Table 2, the proportion of repeat donors was significantly higher among those with hemochromatosis (84%) than among non–health-related donors (77%, P = .03). The frequency of repeat donations in the last 10 years was similar in both groups (P = .46). However, repeat donors with hemochromatosis reported giving significantly more times in the 12 months preceding the survey than repeat non–health-related donors (P<.001). Forty percent of donors with hemochromatosis reported that they intended to make a future donation as soon as they were eligible vs 27% of non–health-related donors. Sixty-one percent of those with hemochromatosis vs 51% of non–health-related donors indicated that they were "very likely"to give again within 3 months of their index donation (P = .008).

The weighted prevalence of unreported deferrable risks was 2.0% for those with hemochromatosis and 3.1% for non–health-related donors. The difference between the 2 groups, as assessed using exact procedures on unweighted data, was not statistically significant (OR, 0.7; 95% CI, 0.2-1.8) (Table 3). Similar results were found when the data were stratified by first-time (P>.99) and repeat (P = .63) donor status (data not shown).

For both groups, the weighted prevalence of positive screening test results for the antibody to hepatitis B core antigen was 0.9%. The weighted prevalence of positive syphilis screening test results was 0.1% among those with hemochromatosis vs 0.2% for non–health-related donors. Among donors reporting hemochromatosis, the prevalence of positive screening test results for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen, human T-lymphotropic virus, and elevated alanine aminotransferase levels was 0.3%, and the combined weighted prevalence for all markers was 1.3%. Among the non–health-related donor groups, these weighted prevalences were 0.6% and 1.6%, respectively.

The results of the exact statistical tests, which are based on unweighted screening test results, showed that the differences in the proportion of positive screening test results between the donors with hemochromatosis and the non–health-related donors was not significant (Table 3). Stratifying the data by first-time vs repeat donor status did not change these findings (P≥.46; data not shown).

Approximately 89% of all donors and 90% of hemochromatosis donors gave at centers whose policy was to defer all hemochromatosis patients. Among the donors with hemochromatosis who gave at these centers, 53% reported that a physician or health care clinician suggested that they donate blood to treat their condition. Of these, 16% claimed to have informed the blood bank staff that they were donating primarily to treat their condition.

COMMENT

The discussion over the acceptability of donations from hemochromatosis patients is becoming more pressing as current trends of increased donor deferrals for behaviors, such as European travel,35 will reduce the number of eligible donors and blood availability. Estimates of the potential donations from hemochromatosis patients vary widely due to limited data but have been as high as 3 million units per year.27 In 1997, the AMA resolved to promote the development of screening guidelines for iron overload and hemochromatosis and to increase the understanding of these conditions.36 Heightened physician awareness of the illness, the acceptance of broader case definitions, and the use of biochemical measures for early detection are leading to the identification of more hemochromatosis cases whose restrictions from donating may further stress the adequacy of the blood supply.

Although hemochromatosis is an exclusionary condition at most US blood centers, and at 7 of the 8 surveyed centers, results from our study suggest that the prevalence of hemochromatosis among blood donors is approximately 0.4%. Many hemochromatosis donors reported giving regularly, possibly at a higher rate than non–health-related donors, and expressed a desire to continue donating. Our estimates suggest that 0.8% of all donations at surveyed centers are from people with diagnosed hemochromatosis.

Since 89% of donors with hemochromatosis gave at centers whose policies stipulate that individuals with the condition are never to donate, our findings suggest that either current risk factor screening does not detect all cases of hemochromatosis or that these donors do not report their illness. There are several possible reasons that individuals with hemochromatosis donate despite restrictions, aside from the possible financial motive. Some may not be fully aware of blood center deferral policies. Among donors with hemochromatosis who gave at blood centers that defer all acknowledged hemochromatosis patients, 16% claimed to have informed the blood bank staff that they were donating for therapeutic reasons. It is unlikely that such a high percentage of donors with admitted hemochromatosis would have been accepted, suggesting some level of miscommunication between donors and the blood bank staff. Donors may not have clearly indicated their diagnosis or may have misunderstood the screening question because donors are not asked directly about hemochromatosis but rather whether they have a blood disease. It is also noteworthy that more than half of these donors reported that they were advised by a health care professional to donate blood as a treatment. Patients may believe that donating blood is appropriate if so directed. Clinicians, in turn, may be unfamiliar with blood center policies or may believe that such policies are unwarranted. Although not recommending that patients with hemochromatosis should donate, the recent AMA recommendation does encourage physicians to explain to their patients that blood from hemochromatosis patients is not necessarily unsuited for direct transfusion.13 Nevertheless, there have been anecdotal reports of physicians advising their patients to conceal their illness to donate.37 These findings suggest that physicians can play an important role by referring patients with hemochromatosis to blood collection centers that permit such patients to donate.

Although motivations for donating are complex, health maintenance appeared to have an important influence on donation behaviors at all study centers; nearly half of the donors with hemochromatosis reported giving primarily for therapeutic reasons. The remainder indicated that donating was unrelated to their health, suggesting that their motivations were probably similar to that of other donors. While our data suggest that as many as 0.4% of donors have been diagnosed as having hemochromatosis and that a substantial number reported donating for therapeutic reasons, we found no evidence to conclude that donors with hemochromatosis present a greater risk to blood safety than non–health-related donors do. The rates of unreported deferrable risks were not significantly different between the 2 groups nor were the rates of positive screening test results. Furthermore, stratifying the data by first-time and repeat donor status did not change our findings. These data are encouraging given that one of the primary reasons health care professionals are concerned about accepting blood from patients with hemochromatosis is that such patients may be more reluctant than other donors to report deferrable risks.

Methodological considerations in interpreting these data need to be addressed. First, 1 study center used a different deferral criterion for hemochromatosis patients than the other 7. We chose to use the data from this center in our analyses of the characteristics and donation patterns of donors with hemochromatosis and doing so did not impact these findings. Interestingly, the only material change from including these donors was that the prevalence of unreported deferrable risks increased by 50% (from 1% to 2%). Neverthless, using the 2% estimate did not change our conclusions. Second, given that 43% of surveyed donors did not respond, we cannot exclude the possibility that our findings are influenced by selection bias. The response rate, however, was 69% among white donors. Because hemochromatosis has been predominantly diagnosed in this population,7 the likelihood that our findings are representative of donors with hemochromatosis is substantially increased. Third, although the total sample size was 50 276, the number of patients with hemochromatosis and the rates of study outcomes determine our ability to assess differences. Owing to the small number of donors with hemochromatosis and the low outcome rates, our estimates of the proportion of donors with unreported risks or positive screening markers have broad CIs, which make it difficult to detect statistical differences between study groups.

The higher prevalence of first-time donors in the non–health-related donor group could also have affected our findings because repeat donors have consistently been shown to have lower rates of disease markers23,38,39 and unreported deferrable risks than first-time donors.25 However, we found that stratifying our data by first-time and repeat donor status did not change our results. Furthermore, we compared differences in the rates of unreported risks and positive screening test results between donors with hemochromatosis (first-time and repeat) and the safest non–health-related donors (repeat only). Again, we found no significant difference between the 2 groups (data not shown), suggesting that our findings were not likely due to differences in the rate of first-time donors.

It is also important to note that findings from screening tests may not be consistent with findings based on confirmatory results because these tests overestimate the prevalence of infected donors. The rates of repeat reactive donations collected at REDS centers that confirm positive range from 9% for human immunodeficiency virus to 68% for hepatitis B surface antigen. Additionally, results of tests to detect the antibody to hepatitis B core antigen can vary substantially depending on the manufacturer. Nonetheless, these measures are useful in identifying populations at higher risk of transmitting disease, and all donations that screen reactive are discarded.

This study was conducted prior to the FDA's granting variances for hemochromatosis donors. Thus, we could not assess the impact of these policies. Because patients with hemochromatosis can require weekly phlebotomies during the early phase of therapy, it is possible that a donor recently infected with a TTVI may make more than 1 donation before the infection can be detected. Although advances in nucleic acid amplification testing can substantially reduce this risk by detecting infections prior to seroconversion, current pooled nucleic acid amplification testing methods cannot reliably detect major TTVIs within 1 week of infection.40 Consequently, research evaluating the blood safety implications of this policy seems warranted.

Despite these limitations, these data from a large-scale survey of US blood donors suggest that many hemochromatosis patients are routinely donating blood, and although not unequivocal, our findings suggest that donors with hemochromatosis do not present a greater risk to blood safety than other donors.

References
1.
Bothwell TH, MacPhail AP. Hereditary hemochromatosis: etiologic, pathologic, and clinical aspects.  Semin Hematol.1998;35:55-71.
2.
Walker EM, Wolfe MD, Norton ML. Hereditary hemochromatosis.  Ann Clin Lab Sci.1998;28:300-312.
3.
Edwards CQ, Kushner JP. Screening for hemochromatosis.  N Engl J Med.1993;328:1616-1620.
4.
Leggett BA, Halliday JW, Brown NN. Prevalence of haemochromatosis amongst asymptomatic Australians.  Br J Haematol.1990;74:525-530.
5.
McLaren Not Available, Gordeuk VR, Looker AC.  et al.  Prevalence of heterozygotes for hemochromatosis in the white population of the United States.  Blood.1995;86:2021-2027.
6.
Edwards CQ, Griffen LM, Goldgar D.  et al.  Prevalence of hemochromatosis among 11,065 presumably healthy blood donors.  N Engl J Med.1988;318:1355-1362.
7.
Witte DL, Crosby WH, Edwards CQ.  et al.  Practice guideline development task force of the College of American Pathologists: hereditary hemochromatosis.  Clin Chim Acta.1996;245:139-200.
8.
Barton JC, McDonnell SM, Adams PC.  et al.  Management of hemochromatosis.  Ann Intern Med.1998;129:932-939.
9.
Niederau C, Rudolf F, Purschel A. Long-term survival in patients with hereditary hemochromatosis.  Gastroenterology.1996;110:1107-1119.
10.
Powell LW. Hemochromatosis: the impact of early diagnosis and therapy [editorial].  Gastroenterology.1996;110:1304-1307.
11.
Jeffrey G, Adams PC. Blood from patients with hereditary hemochromatosis—a wasted resource?  Transfusion.1999;39:549-550.
12.
Levstik M, Adams PC. Eligibility and exclusion of hemochromatosis patients as voluntary blood donors.  Can J Gastroenterol.1998;12:61-63.
13.
Tan L, Khan MK, Hawk JC.for the Council on Scientific Affairs, American Medical Association.  Use of blood therapeutically drawn from hemochromatosis patients.  Transfusion.1999;39:1018-1026.
14.
Grindon AJ. Blood donation from patients with hemochromatosis.  JAMA.1993;270:880.
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