Maintaining an adequate blood supply requires

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1 BLOOD DONORS AND BLOOD COLLECTION Impact of a policy to permit the return of donors repeat-reactive to the Abbott PRISM antibody to hepatitis B core antigen assay Sheila F. O Brien, Qi-Long Yi, Wenli Fan, Margaret A. Fearon, Vito Scalia, and Mindy Goldman BACKGROUND: The expected donor loss from recent implementation of antibody to hepatitis B core antigen (anti-hbc) testing in Canada was uncertain but potentially significant based on US experience. To reduce donor loss from false-reactive tests, repeat-reactive donors without other evidence of infection were eligible to return. The aim was to evaluate the impact of anti- HBc testing on donor loss and to evaluate the effectiveness of this policy. STUDY DESIGN AND METHODS: For each donor in the first year of implementation (April 9, 2005-April 8, 2006) repeat-reactive for the presence of anti-hbc only but eligible to return (screening test for hepatitis B surface antigen negative, plus not reactive to antibody to hepatitis B surface antigen [anti-hbs] and hepatitis B virus [HBV] DNA supplemental tests), 10 matched donors not reactive to the anti-hbc assay were selected. Return rates over 2 years were compared using conditional logistic regression. Testing outcomes were tabulated. RESULTS: Over the first year of testing, 412,236 donors (951,423 donations) were tested for anti-hbc, and 4,489 donors were repeat-reactive (1.3% of firsttime donors, 1.0% of repeat donors). Of these 85.6 percent were also reactive for the presence of anti-hbs and/or HBV DNA supplemental tests leaving less than 15 percent eligible to return, of whom 73 percent returned (vs. 90% of controls, p < 0.001). Of the 300 anti-hbc repeat-reactive returning donors, 74 percent were anti-hbc repeat-reactive again (thus permanently deferred), 19 percent were deferred for other reasons versus 14 percent of controls (p < 0.05), and 7 percent (21 donors) did not react and were eligible to continue donating. CONCLUSION: Most donors repeat-reactive for the presence of anti-hbc likely have past exposure to HBV. If eligible, most are willing to return, but likely to test anti-hbc repeat-reactive again. Maintaining an adequate blood supply requires a balance between donor recruitment and retention and donor deferral. In Canada the practice has been to permanently defer all donors who test repeat-reactive to screening tests for transmissible disease even when confirmatory testing indicated false reactivity. However, concerns that repeat-reactive test results may predict early stage infection are now largely refuted 1 and electronic management of data is improved and donor reentry is possible in other countries such as the United States, 2 but publications evaluating the willingness of donors to return after notification of a false-reactive test are scant. At Canadian Blood Services, antibody to hepatitis B core antigen (anti-hbc) testing was implemented for all units in April 2005 and we have previously reported that the risk of potentially infectious units being released for transfusion was reduced by at least as much as expected (1 per 26,900 donations). 3 With the implementation of universal, government-sponsored hepatitis B vaccination programs in many provinces, it is expected that the prevalence of hepatitis B infection will gradually fall among Canadian-born individuals, as well as in immigrant children who have access to free hepatitis B vaccination in middle school. 4,5 Hence, the number of blood donors exposed to hepatitis B is also expected to fall over time. However, it was considered to be important to detect the small number of donors who have had hepatitis B in the From the Departments of Epidemiology & Community Medicine and Pathology & Laboratory Medicine, University of Ottawa, Ottawa, Ontario; the Department of Pathology & Laboratory Medicine, University of Toronto, Toronto, Ontario; and Canadian Blood Services, Ottawa, Ontario, Canada. Address reprint requests to: Sheila F. O Brien, National Epidemiology and Surveillance, Canadian Blood Services, 1800 Alta Vista Drive, Ottawa, ON K1G 4J5, Canada; sheila.o brien@blood.ca. Financial support: Canadian Blood Services. Received for publication July 22, 2008; revision received August 26, 2008; and accepted August 26, doi: /j x TRANSFUSION 2009;49: Volume 49, February 2009 TRANSFUSION 271

2 O BRIEN ET AL. past and still carry detectable viral DNA, because they may pose a risk for transfusion transmission to an immunocompromised recipient. 3 Before implementation there were little published data to indicate the donor loss that could be expected using the Abbott PRISM assay (Abbott Diagnostics Division, Wiesbaden, Germany) for anti-hbc testing, although the use of reducing agents (cysteine in this assay) has been well documented in eliminating most false-positive reactions. 5 In the United States with the use of less specific assays, the false reactivity rate may be as high as 35 percent of repeat-reactive donations, 6 and to reduce donor loss from falsely reactive tests the American Red Cross has a two-strike policy that permits donors with an anti-hbc reactive test to return for a second donation attempt, with permanent deferral only after two anti- HBc reactive donations (two strikes). 7 With implementation of anti-hbc testing at Canadian Blood Services, it was uncertain what the combined donor loss from falsereactive tests and true-positive tests would be since the anti-hbc positive rate in the general Canadian population is unknown, although some regional reports of subpopulations appear to have rates greater than 5 percent. 8 Other countries with low prevalence such as Germany and New Zealand estimated that anti-hbc screening would result in a loss of 2 and 6.7 percent of otherwise acceptable donors. 9 We attempted to minimize donor loss due to false-reactive tests with the implementation of anti-hbc testing using a modified two-strike policy that permitted donors with a repeat-reactive test to anti-hbc to return to donate a second time if there was no other evidence of past or present infection (defined as undetectable antibody to hepatitis B surface antigen [anti-hbs], hepatitis B surface antigen [HBsAg], or hepatitis B virus [HBV] DNA). In this way, all donors with high potential to be truly positive were permanently deferred, but donors who may have false-reactive results were eligible to return for a second donation attempt. We aimed to determine the anti-hbc repeat-reactive rate in an untested donor population, to assess the impact of the repeat-reactive test on donors return behavior and the benefit of the modified twostrike policy in mitigating the donor loss due to the implementation of this new assay. MATERIALS AND METHODS Testing method All blood donations were screened for the presence of HBsAg using the Abbott PRISM HBsAg assay (Abbott Diagnostics Division) and repeat-reactive donations were tested with the Abbott PRISM HBsAg confirmatory assay. As of April 9, 2005, all blood donations were also screened for anti-hbc using the Abbott PRISM HBcore assay (Abbott Diagnostics Division). At Canadian Blood Services, HBV DNA testing is not carried out on all samples. Only samples repeat-reactive for the presence of anti-hbc are further tested using two supplemental assays: anti- HBs and HBV DNA using the Abbott AUSAB enzyme immunoassay (Abbott Laboratories Diagnostics Division, Abbott Park, IL) and COBAS AmpliScreen HBV test (Roche Molecular Systems, Inc., Branchburg, NJ), respectively. The analytic sensitivity of the HBV DNA assay method used is approximately 80 copies per ml. Blood donations that were repeat-reactive for the presence of anti-hbc or HBsAg were not released into inventory. Donor notification and deferral Donors who had a repeat-reactive test to HBsAg were permanently deferred irrespective of confirmatory testing. Donors who had a repeat-reactive test to anti-hbc and detectable anti-hbs and/or HBV DNA were also permanently deferred. However, donors who had a repeat-reactive test for anti-hbc only but were not reactive to anti-hbs and HBV DNA supplemental testing were eligible to return to make a second donation because they were considered to be more likely to have false reactivity more likely to resolve in a short time. These donors were informed of their repeat-reactive test result in a standard letter that explained that the donor may have been exposed to hepatitis B at some point in the past or that it may be a false-reactive test. The donor was informed that she or he was still eligible to donate as long as all screening test results on each future donation did not react. Thus, to obtain a second test, the donor made a second donation. There was no indication to the donor how likely a reactive anti-hbc test would be on the second donation, because initially we did not have that data. Donors reporting a history of hepatitis B in response to direct questioning before donation are permanently deferred. National Epidemiology Donor Database The National Epidemiology Donor Database is maintained with computer software (SAS, SAS Institute, Inc., Cary, NC) and contains donation and test data as well as demographic data such as age and sex on all Canadian blood donors except those in the province of Québec. In this study all allogeneic blood donations (whole blood, plasma apheresis, and plateletpheresis donations) were included. Statistical analysis All donors making a donation after implementation of anti-hbc testing on April 9, 2005, were identified. The rate of anti-hbc repeat-reactive donations was calculated as the number of donors with a repeat-reactive index donation divided by the total donations per time period and expressed as a percentage. Rates were calculated sepa- 272 TRANSFUSION Volume 49, February 2009

3 IMPACT OF ANTI-HBc TWO-STRIKE POLICY rately for first-time and repeat donors and the trend was estimated using a Poisson model. The percentage of anti- HBc reactive donors was also calculated for different geographic regions, for age groups and for males and females, and compared by fitting Poisson models. To examine the impact of the notification of a repeatreactive anti-hbc screening test on donor return behavior, we carried out a nested case-control analysis. All anti- HBc reactive donors eligible to return who made their index repeat-reactive donation during the first year of implementation (April 9, 2005-April 8, 2006) were identified and for each donor 10 control donors were selected from the donor base. Controls were matched to cases on the basis of age ( 5 years) donation date ( 2 weeks), sex, donation type, blood center, and donation status (first time or repeat). All donors in the study were tracked until May 30, A conditional logistic model was used to compare the returning rate and deferral rates between donors with repeat-reactive anti-hbc results eligible to return and their matched controls. The returning rate was also compared using a Cox regression model with both matching group and return time considered. The test results were tabulated, as well as other deferral data to assess the rate of successful donation in the donors with an anti-hbc reactive result that were eligible to return and to compare these with control donors. RESULTS Figure 1 shows the percentage of donors who were repeat-reactive for anti-hbc by month since testing began. During the first year after implementation, 4489 donors (1.1%) were repeat-reactive. The repeat-reactive rate in first-time donors remained fairly constant with a mean of 1.3 percent over the 3 years of the study, whereas in repeat donors the rates drop down quickly with time (p < 0.001). On their first occasion to be tested 1.03 percent of repeat donors tested anti-hbc repeat-reactive, so that over time the denominator for the repeat-reactive donation rate shown in Fig. 1 included more donations from previously tested repeat donors. Hence the rate in repeat donors decreased dramatically in the months after implementation, so that after 2 years the rate was only approximately 0.1 percent. Of all 8555 anti-hbc reactive donations over the 3 years of the study (excluding both those returned after an initial positive donation and HBsAg-positive donations), 3354 (39.2%) were from firsttime donors. Table 1 shows the number and percentage of anti- HBc reactive donors by region, by age group, and by sex in first-time and repeat donors since April 9, Percentages represent the percentage of all donors in that particular stratum. The percentage of anti-hbc reactive donors was highest in the British Columbia and central Ontario Anti-HBc-reactive donations (%) Apr 05-Oct 06-Apr 06-Oct 07-Apr Date 07-Oct 08-Apr Fig. 1. The percentage of anti-hbc reactive donations in first-time and repeat donors (April 2005-May 2008;, first-time donors;, repeat donors). Volume 49, February 2009 TRANSFUSION 273

4 O BRIEN ET AL. TABLE 1. The number (%) of anti-hbc reactive donations by geographic region, age group, and sex (April 9, 2005, to May 30, 2008) Number of anti-hbc reactive donations Variable First-time donors Repeat donors Region British Columbia 672 (1.95) 1048 (0.32) Alberta 538 (1.21) 756 (0.16) Manitoba and Saskatchewan 228 (0.64) 420 (0.12) Southern Ontario 400 (0.81) 676 (0.13) Central Ontario 1222 (2.25) 1620 (0.37) Northern and Eastern Ontario 185 (0.74) 394 (0.14) Atlantic provinces 109 (0.38) 287 (0.08) Total 3354 (1.24) 5201 (0.19) Age (years) (0.48) 426 (0.09) (1.87) 728 (0.18) (2.26) 1475 (0.19) (2.69) 2572 (0.23) Total 3354 (1.24) 5201 (0.19) Sex Females 1408 (0.96) 2188 (0.19) Males 1946 (1.57) 3013 (0.19) Total 3354 (1.24) 5201 (0.19) Variable TABLE 2. Comparison of returning rate of donors eligible to return after an anti-hbc reactive donation and matched controls* Anti-HBc reactive donors eligible to return (n = 413) regions (which include the cities of Vancouver, British Columbia, and Toronto, Ontario, respectively), followed by Alberta, and was lowest in Atlantic Canada. This pattern was observed in both first-time and repeat donors but the percentage in repeat donors was lower than in first-time donors in each region. The percentage of anti- HBc reactive donors increased with age in both first-time and repeat donors, but the percentage in repeat donors was less for each age group compared with first-time donors. In first-time donors the percentage of males with an anti-hbc reactive test was greater than females but in repeat donors the percentage was equally low in both males and females. Of donors testing repeat-reactive for the presence of anti-hbc over the 3 years, 85.2 percent were also anti- HBs reactive. Most donors who were HBV DNA positive were also HBsAg-positive (81%), and there were 41 who were HBsAg-nonreactive but reactive for the presence of both anti-hbc and HBV DNA. Although most donors that were anti-hbc reactive were identified on their first donation tested, there were some donors who initially tested anti-hbc nonreactive on a donation and then repeatreactive on a subsequent donation. Over the 3 years of testing, there were 713,658 donors anti-hbc nonreactive on their first testing occasion who made at least one more donation that was tested. In total, 543 (0.076%) were subsequently repeat-reactive and 175 (32%) of these were identified on their next donation. Of the 543 donors, 55 were deferred for other reasons and 332 (61%) were eligible to return for another donation and 230 were tested with 96 (42%) having a repeat-reactive result (and thus permanently deferred). There was no difference (p = 0.549) in median time and range between the first anti-hbc reactive test and the second reactive test. This was 137 (range, ) days for donors who tested reactive on the first occasion of testing compared with 140 (range, ) days for those whose first test did not react and had a reactive test on a later donation. Table 2 shows the results of the nested case-control analysis and the donation outcome of eligible anti- HBc reactive donors who returned for Control group (n = 4130) p Value Returned 300 (72.6) 3718 (90.1) <0.001 Returned within 1 year 242 (58.6) 3347 (81.2) <0.001 Outcome of return Number of donors Deferred 56 (18.7) 504 (13.6) Anti-HBc reactive 223 (74.3) 1 (0.03) <0.001 Successful donation 21 (7.0) 3213 (86.4) <0.001 * Data are reported as number (%). Donors that were anti-hbc reactive and eligible to return in the first 12 months of testing were tracked for an additional 2 years. a second donation attempt. Of 4489 donors with anti-hbc reactive tests, there are only 434 donors with negative anti-hbs, negative HBsAg, and negative HBV DNA test results. Of these 434 donors, 21 donors were deferred for either another transmissible disease marker or malaria risk, leaving only 413 who were eligible to return. More than two-thirds of eligible donors with a repeat-reactive test returned to donate although this was less than for matched controls (72.6% vs. 90.1%). The return rates were somewhat higher in repeat donors than the first-time donors (75.4% vs. 63.6% in eligible anti-hbc reactive donors and 93.8% vs. 77.5% in controls). Of the 300 donors who returned, more were deferred for other reasons compared with controls (18.7% vs. 13.6%), and the majority of those who made a donation were anti-hbc reactive a second time, with only 21 of the 300 (7.0%) successfully donating compared with 86.4 percent of controls. Of these 21 donors who were able to donate, 19 later returned for another donation and 16 tested repeat-reactive to anti-hbc and were permanently deferred. Furthermore, of the donors with one previous anti-hbc reactive test that were deferred, 45 percent (25 donors) returned of whom 20 (80.0%) were 274 TRANSFUSION Volume 49, February 2009

5 IMPACT OF ANTI-HBc TWO-STRIKE POLICY repeat-reactive again, and 2 were permanently deferred for other reasons leaving only 3 of these returning donors. After also taking into account other permanent deferrals, of 413 donors repeat-reactive for the presence of anti-hbc only 6 (1.5%) donors were eligible to donate that were still donating at the end of the study period. DISCUSSION Implementation of anti-hbc testing resulted in approximately 1 percent loss of all donors and an ongoing loss of first-time donors of at least 1 percent per year. Most eligible donors notified of their reactive screening test returned to donate although the rate was less than that of matched control donors. However, of those donors with anti-hbc repeat-reactive results, the rate of successful donation was very low with the majority testing repeatreactive to the presence of anti-hbc a second time and thus permanently deferred. Anti-HBc testing protocols are quite variable across jurisdictions and blood operators. The American Red Cross has an (unmodified) two-strike policy that permits donors repeat-reactive to the presence of anti-hbc to make a second donation attempt and does not depend on anti-hbs or HBV DNA test results. 7 In Japan, where the donor loss from deferral could compromise the sufficiency of the blood supply, anti-hbc reactive donors are accepted if they have an anti-hbs titer of greater than 2 4 (approx. 200 miu/ml), and if HBV nucleic acid testing is negative, even if the anti-hbc titer is greater than In the United Kingdom, a selective testing policy is applied in which only donors with increased risk in the past 6 to 12 months are tested for anti-hbc and if positive only deferred if their anti-hbs levels are low (J. Barbara, National Blood Service, personal communication, 2008). The variability in approach is likely a reflection of HBV prevalence and expected impact on sufficiency, different regulatory frameworks, and different risk tolerance. Nearly 90 percent of donors repeat-reactive for the presence of anti-hbc in our study were also reactive for the presence of anti-hbs similar to the proportion reported in a US study 6 and suggestive of a true exposure. Although a donor vaccinated against HBV would have anti-hbs and could conceivably have a false-reactive anti- HBc test, this is unlikely to be the case for the most part because the regional distribution of reactive tests followed a similar distribution to that of HBsAg positivity, 4 and the percentage of reactive tests in each age group increased progressively as is expected due to increased opportunity for exposure with age. 10 In Canada, first-time donors are more similar to the Canadian general population in terms of country of birth; thus there are a higher proportion of first-time donors who were born in a country where HBV is more prevalent (especially Asia and Africa) 4 than there are repeat donors. Thus the somewhat higher percentage of first-time donors with anti-hbc reactive tests was not unexpected, and the regional correlation of anti-hbc reactive tests and the correlation with increasing age are consistent with a pattern expected of true-positive donations. Hence, the data suggest that most repeat-reactive donations represent true exposure. Compared with donors who tested repeat-reactive initially, only a small percentage of donors tested repeatreactive after a negative test. This indicates that the bulk of the repeat-reactive donations are identified when testing is initiated leaving a smaller residual loss of previously tested donors. In donors who had previously tested nonreactive, fewer had other hepatitis B markers perhaps suggesting that these are more likely to be false-positive anti-hbc, but they could also represent low-level anti- HBc, near the cutoff. Some donors with a history of hepatitis B infection may be carrying the infection even when neither HBV DNA nor HBsAg are detectable in the blood. 11 Thus, deferral of donors with anti-hbc reactive tests plus other indicators suggestive of past infection may be prudent. When the anti-hbc reactive result is a false-reactive, these donors clearly pose no risk to the safety of the blood supply. However, as most donors will be repeat-reactive for the presence of anti-hbc on their second attempt to donate, it is neither a good use of resources nor is it ethical to continue to take a blood donation from someone who has a low probability of donating a usable unit. Hence, once a donor has tested repeat-reactive twice, we considered it reasonable to defer them. Overall the rate of donor loss was sustainable, but represents an ongoing loss of donors that adds to the already considerable list of donor exclusions 12,13 and further reduces the eligible donor population. 14 The fact that the return rate in eligible anti-hbc reactive donors was less than in controls is consistent with reports of other negative experiences such as deferral 15 and donor reactions; 16,17 however, the 72 percent of anti-hbc reactive only donors who returned is still a sizeable proportion, and had the donors been able to successfully donate, the modified two-strike policy would have been reasonable. Before this study, there were little data that could be used to predict the donor return rate. Thus in a recent review, Kiely and Wood 1 suggested that it may be better to delay informing donors until they tested repeatreactive on a second donation and were deferred. Our data suggest that a clear concise letter allows the donor to be informed with only a small drop in return rate. Our study did not assess donors motivation to return, but people who donate blood may have an altruistic identity 18 possibly overriding negative feelings about the information; they may have feelings of confusion and rejection at the possibility of deferral 19 and wish to assert their interest in continuing to donate or they may be motivated by curiosity about their test results. Volume 49, February 2009 TRANSFUSION 275

6 O BRIEN ET AL. In our study donors with repeat-reactive results were very likely to test repeat-reactive a second time, and so the return policy was of little benefit in maintaining the blood supply. However, donor reentry may at some point be feasible for some markers such as human immunodeficiency virus and hepatitis C virus where negative confirmatory testing can be used to clear the donor (although such a program is not yet in place at Canadian Blood Services). Because false-reactive tests tend to be specific to the screening assay and are often triggered by nonspecific antibody reactivity, 1,20 the fairly high return rates in our study may suggest that donor reentry has promising potential, particularly if the use of other testing, such as a screening kit from a different manufacturer, is a possibility. 21 It should be noted that a study of a potential reentry protocol involving follow-up testing of donors deferred for anti-hbc reactive tests in the United States, mostly from several years earlier, saw only a 12 percent return rate. 7 Thus our results may suggest that reentry protocols are likely to yield higher donor return rates if available shortly after deferral, and reduced donor loss when a more specific screening test is implemented may be primarily from deferral reduction going forward. In our experience, the implementation of the Abbott PRISM anti-hbc assay resulted in approximately 1 percent of donors testing repeat-reactive, of which most appear to represent true exposure to hepatitis B. The specificity of the PRISM anti-hbc assay has therefore shown to be much improved over the older assays used in the implementation of this testing in the United States. Thus only slightly more than 10 percent of anti-hbc repeat-reactive donors were eligible to return, and as nearly all of these tested repeat-reactive a second time and were permanently deferred, the modified two-strike policy was not effective in mitigating donor loss from the implementation of this assay. However, because more than two-thirds of the eligible donors returned for a second donation attempt, donor reentry programs for other markers with donors less likely to test repeat-reactive again, or that use algorithms involving a different assay for the same marker, may be more successful in reintegrating false-positive donors. REFERENCES 1. Kiely P, Wood E. Can we improve the management of blood donors with non-specific reactivity in viral screening and confirmatory assays? Transfus Med Rev 2005;19: U.S. Food and Drug Administration. Guidance for Industry. Nucleic acid testing (NAT) for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV): testing, product disposition, and donor deferral and reentry [PDF version]. Rockville (MD): FDA; [cited 2008 May 15]. Available from: nathivhcv.htm 3. O Brien SF, Fearon MA, Yi QL, Fan W, Scalia V, Muntz IR, Vamvakas EC. Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience. Transfusion 2007;47: O Brien SF, Xi G, Fan W, Yi QL, Fearon MA, Scalia V, Goldman M. Epidemiology of hepatitis B in Canadian blood donors. Transfusion 2008; Jul 11. [Epub ahead of print]. 5. Spronk AM, Schmidt L, Krenc C, Pavlisjenkins L, Brady J, Taskar S, Angusfinn L, Mimms L. Improvements in detection of antibody to hepatitis B core antigen by treating specimens with reducing agent in an automated microparticle enzyme immunoassay. J Clin Microbiol 1991;29: Kleinman SH, Kuhns MC, Todd DS, Glynn SA, McNamara A, DiMarco A, Busch MP. Frequency of HBV DNA detection in US blood donors testing positive for the presence of anti-hbc: implications for transfusion transmission and donor screening. Transfusion 2003;43: Stramer SL, Dodd RY. Donor reentry. In: Eder A, Bianco C, editors. Screening blood donors: science, reason and the donor history questionnaire. Bethesda (MD): AABB Press; p Dawar M, Patrick DM, Bigham M, Cook D, Krajden M, Ng H. Impact of universal preadolescent vaccination against hepatitis B on antenatal seroprevalence of hepatitis B markers in British Columbia women. CMAJ 2003;18: Comanor I, Holland P. Hepatitis B virus blood screening: unfinished agendas. Vox Sang 2006;91: McQuillan GM, Coleman PJ, Kruszon-Moran D, Moyer LA, Lambert SB, Margolis HS. Prevalence of hepatitis B virus infection in the United States: the national health and nutrition examination surveys, 1976 through Am J Public Health 1999;89: Kuhns MC, Busch MP. New strategies for blood donor screening for hepatitis B virus: nucleic acid testing versus immunoassay methods. Mol Diagn Ther 2006;10: Custer B, Johnson ES, Sullivan SD, Hazlet TK, Ramsey SD, Hirschler NV, Murphy EL, Busch MP. Quantifying losses to the donated blood supply due to donor deferral and miscollection. Transfusion 2004;44: O Brien SF, Ram SS, Vamvakas EC, Goldman M. The Canadian blood donor health assessment questionnaire: lessons from history, application of cognitive science principles, and recommendations for change. Transfusion Med Reviews 2007;21: Riley W, Schwei M, McCullough J. The United States potential blood donor pool: estimating the prevalence of donor-exclusion factors on the pool of potential donors. Transfusion 2007;47: Custer B, Chinn A, Hirschler NV, Busch MP, Murphy EL. The consequences of temporary deferral on future whole blood donation. Transfusion 2007;47: France JL, France CR, Himawan LK. A path analysis of 276 TRANSFUSION Volume 49, February 2009

7 IMPACT OF ANTI-HBc TWO-STRIKE POLICY intention to redonate among experienced blood donors: an extension of the theory of planned behaviour. Transfusion 2007;47: Newman BH, Pichette S, Pichette D, Dzaka E. Adverse effects in blood donors after whole-blood donation: a study of 1000 blood donors interviewed 3 weeks after whole-blood donations. Transfusion 2003;43: Piliavin JA, Callero PL. Giving blood: the development of an altruistic identity. Baltimore (MD): Johns Hopkins University Press; Whittaker S, Carter N, Arnold E, Shehata N, Webert KE, DiStefano L, Heddle NM. Understanding the meaning of permanent deferral for blood donors. Transfusion 2008;48: Kiely P, Stewart Y, Castro L. Analysis of voluntary blood donors with biologic false reactivity on chemiluminescent immunoassays and implications for donor management. Transfusion 2003;43: Moore MC, Howell DR, Barbara JA. Donors whose blood reacts falsely positive in transfusion microbiology screening assays need not be lost to transfusion. Transfus Med 2007;17:55-9. Volume 49, February 2009 TRANSFUSION 277