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Background: State of the Science (SoS) meetings are used to define and highlight important unanswered scientific questions. The National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and the Office of the Assistant Secretary for Health (OASH), Department of Health and Human Services held a virtual SoS in transfusion medicine (TM) symposium., Study Design and Methods: In advance of the symposium, six multidisciplinary working groups (WG) convened to define research priorities in the areas of: blood donors and the supply, optimizing transfusion outcomes for recipients, emerging infections, mechanistic aspects of components and transfusion, new computational methods in transfusion science, and impact of health disparities on donors and recipients. The overall objective was to identify key basic, translational, and clinical research questions that will help to increase and diversify the volunteer donor pool, ensure safe and effective transfusion strategies for recipients, and identify which blood products from which donors best meet the clinical needs of specific recipient populations., Results: On August 29-30, 2022, over 400 researchers, clinicians, industry experts, government officials, community members, and patient advocates discussed the research priorities presented by each WG. Dialogue focused on the five highest priority research areas identified by each WG and included the rationale, proposed methodological approaches, feasibility, and barriers for success., Discussion: This report summarizes the key ideas and research priorities identified during the NHLBI/OASH SoS in TM symposium. The report highlights major gaps in our current knowledge and provides a road map for TM research., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: The supply of blood in many low- and middle-income nations in Sub-Saharan Africa (SSA) does not meet the patient care needs. Lack and delay of blood transfusion cause harm to patients and slow the rate of progress in other parts of the health system. Recognizing the power of implementation science, the BLOODSAFE Program was initiated which supports three SSA research study teams and one data coordinating center (DCC) with the goal to improve access to safe blood transfusion in SSA., Study Design and Methods: The study team in Ghana is focusing on studying and decreasing iron deficiency in blood donors and evaluating social engagement of blood donors through different approaches. The study team in Kenya is building a "vein to vein" workflow model to elucidate and devise strategies to overcome barriers to blood donation and improve infrastructural components of blood product production and use. The Malawi team is studying the infectious disease ramifications of blood donation as well as blood donor retention strategies aimed at blood donors who commence their donation career in secondary schools., Results and Discussion: Together the project teams and the DCC work as a consortium to support each other through a shared study protocol that will study donor motivations, outcomes, and adverse events across all three countries. The BLOODSAFE Program has the potential to lead to generalizable improvement approaches for increasing access to safe blood in SSA as well as mentoring and building the research capacity and careers of many investigators., (© 2022 AABB.)

Background: Previous data, although scant, indicated that the incidence of HIV in China has increased over the past decade. There is a growing concern about the impact of the HIV epidemic on blood safety., Methods and Materials: We used donation data from five geographically-disperse blood centers in 2013-2016 participating in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) China program to estimate HIV prevalence and incidence among blood donors. Multivariable logistic regression model was used to examine factors associated with HIV infection in Chinese blood donors., Results: The overall HIV prevalence among first-time donors from 2013 through 2016 was 68.04 per 100,000 donors (95% CI 61.68-74.40). The HIV incidence rate was estimated to be 37.93 per 100,000 person-years (95% CI 30.62-46.97) among first-time donors and 20.55 per 100,000 person-years (95% CI 16.95-24.91) among repeat donors. There was substantial variation in HIV prevalence and incidence rates across blood centers. Multivariable logistic regression results showed that among first-time donors, being male, older than 25 years, minority ethnicity, less than college education, and certain occupations (commercial services, factory workers, retired, unemployed, or self-employed) were associated with positive HIV confirmatory testing results., Conclusion: HIV prevalence and incidence among blood donors remain low in the selected five regions in China; however, an increasing trend is observed at some blood centers. It is important to monitor HIV epidemiology in Chinese blood donors on a continuous basis, especially among populations and regions of higher risk., (© 2019 AABB.)

In April 2017, a workshop sponsored by the National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources, and the Center for Translation Research and Implementation Science was held to discuss blood availability and transfusion safety in low- and middle-income countries (LMICs). The purpose of the workshop was to identify research opportunities for implementation science (IS) to improve the availability of safe blood and blood components and transfusion practices in LMICs. IS describes the late stages of the translational research spectrum and studies optimal and sustainable strategies to deliver proven-effective interventions. Regional working groups were formed to focus on opportunities and challenges in East Africa, Central/West Africa, Middle East and North Africa, Latin America and the Caribbean, Southeast Asia, Western Pacific Asia, Eastern Europe, and Central Asia. The need for an "adequate supply of safe blood" emerged as the major overriding theme. Among the regional working groups, common cross-cutting themes were evident. The majority of research questions, priorities, and strategies fell into the categories of blood availability, blood transfusion safety, appropriate use of blood, quality systems, health economics and budgeting, and training and education in IS. The workshop also brought into focus inadequate country-level data that can be used as the basis for IS initiatives. A mixed approach of needs assessment and targeted interventions with sufficient evidence base to move toward sustainment is an appropriate next step for blood availability and transfusion safety research in LMICs., (© 2018 AABB.)

On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three "classical" transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Before the meeting, four working groups, one for each area, prepared five major questions for discussion along with a list of five to 10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in keynote lectures, small-group breakout sessions, and large-group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross-cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine., (© 2015 AABB.)

Background: In 2007, a total of 10,508 suspected dengue cases were reported in Puerto Rico. Blood donations were tested for dengue virus (DENV) RNA and recipients of RNA-positive donations traced to assess transfusion transmission., Study Design and Methods: Blood donation samples from 2007 were maintained in a repository and tested individually for DENV RNA by transcription-mediated amplification (TMA); a subset was further tested by an enhanced TMA (eTMA) assay. TMA-reactive samples were considered confirmed if TMA (including eTMA) was repeat reactive (RR). All TMA-RR samples were tested by quantitative, DENV type-specific reverse transcriptase-polymerase chain reaction (RT-PCR) and for anti-DENV immunoglobulin (Ig)M by enzyme-linked immunosorbent assay. Samples positive by RT-PCR were further tested for infectivity in mosquito cell culture. Patients receiving components from TMA-RR donations were followed., Results: Of 15,350 donation samples tested, 29 were TMA-RR for a prevalence of 1 per 529 (0.19%). DENV Types 1, 2, and 3 with viral titers of 10(5) to 10(9) copies/mL were detected by RT-PCR in 12 samples of which all were infectious in mosquito culture. Six TMA-RR samples were IgM positive. Three of the 29 recipients receiving TMA-RR donations were tested. One recipient in Puerto Rico transfused with red blood cells containing 10(8) copies/mL DENV-2 became febrile 3 days posttransfusion and developed dengue hemorrhagic fever. The recipient was DENV-2 RNA positive by RT-PCR; both the donor and the recipient viruses had identical envelope sequences., Conclusions: High rates of viremia were detected in blood donors in Puerto Rico coupled with the first documented transfusion transmission of severe dengue disease, suggesting that further research on interventions is needed., (© 2012 American Association of Blood Banks.)

Background: The American Red Cross implemented hepatitis B virus (HBV) minipool (MP)-nucleic acid testing (NAT) in June 2009, in addition to existing tests for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti-HBc). The value of all three tests was evaluated., Study Design and Methods: HBsAg, anti-HBc, and HBV DNA (Ultrio MP-NAT, Gen-Probe/Novartis) donation results were analyzed during a 12-month period (July 1, 2009-June 30, 2010). Additional testing by individual-donation (ID) polymerase chain reaction (PCR) to confirm donor infection was performed when any HBV screening test was reactive or positive, except in the case of HBsAg neutralization-positive, anti-HBc-reactive samples. Numbers of blood donations identified as reactive or positive versus nonreactive or negative were compared., Results: Of about 6.5 million donations, 699 were defined as from HBV-infected donors, of which 64% (444) were reactive for all three markers. More than 99% (697) had reactivity to one or both serologic tests with 68% (477) showing reactivity by MP-NAT. Only two donations were DNA-positive, seronegative NAT-yield donations (1 per 3.23 million), fewer than expected (p = 0.0075). Among MP-NAT-reactive donors, only small numbers represented early infection (2 or 0.4% with negative serology and 10 or 2.1% who were HBsAg confirmed positive, anti-HBc nonreactive). Of the 142 occult HBV-infected donors, 85% were MP-NAT nonreactive requiring ID-PCR for detection (121 or 54.5% of all MP-NAT nonreactives vs. 21 or 4.4% of all MP-NAT reactives)., Conclusions: The HBV DNA-positive yield rate from MP-NAT was lower than expected, likely representing the rarity of such findings even in very large studies. With the implementation of HBV MP-NAT, the value of maintaining anti-HBc for the detection of low-level HBV DNA-positive donors was confirmed; however, HBsAg screening showed no blood safety value., (© 2012 American Association of Blood Banks.)

Background: When xenotropic murine leukemia virus-related virus (XMRV) was first reported in association with chronic fatigue syndrome, it was suggested that it might offer a risk to blood safety. Thus, the prevalence of the virus among blood donors and, if present, its transmissibility by transfusion need to be defined., Study Design and Methods: Two populations of routine blood donor samples (1435 and 13,399) were obtained for prevalence evaluations; samples from a linked donor-recipient repository were also evaluated. Samples were tested for the presence of antibodies to XMRV-related recombinant antigens and/or for XMRV RNA, using validated, high-throughput systems., Results: The presence of antibodies to XMRV could not be confirmed among a total of 17,249 blood donors or recipients (0%; 95% confidence interval [CI], 0%-0.017%); 1763 tested samples were nonreactive for XMRV RNA (0%; 95% CI, 0%-0.17%). Evidence of infection was absent from 109 recipients and 830 evaluable blood samples tested after transfusion of a total of 3741 blood components., Conclusions: XMRV and related murine leukemia virus (MLV) markers are not present among a large population of blood donors and evidence of transfusion transmission could not be detected. Thus, these viruses do not currently pose a threat to blood recipient safety and further actions relating to XMRV and MLV are not justified., (© 2012 American Association of Blood Banks.)

Background: Blood donor screening with enzyme immunoassays (EIAs) for antibodies to human T-lymphotropic virus (HTLV)-I, and later to HTLV-I/II, has led to the unnecessary deferral of tens of thousands of individuals. The licensure of the Abbott PRISM HTLV-I/HTLV-II chemiluminescent immunoassay (ChLIA) may permit the reinstatement of historically deferred donors., Study Design and Methods: The efficacy of a reentry algorithm involving a follow-up sample from EIA-deferred donors testing HTLV-I/II ChLIA nonreactive was evaluated using 386 serologic confirmed-positive samples archived since the inception of anti-HTLV donor screening. Reactivity of the 386 samples by the ChLIA, when coupled with the package insert sensitivity data, may be used to demonstrate efficacy of the reentry algorithm. Donor incidence was also examined from 2008 through 2009 to evaluate changes to the existing HTLV screening policy., Results: From January 1, 1995, to April 28, 2008, a total of 64,052 donors to the American Red Cross were deferred solely because of HTLV EIA false positivity, representing more than 130,000 US donors. HTLV ChLIA identified 386 confirmed-positive donations from 386 randomly selected donors representing reactivity to both the bioMérieux and the Abbott HTLV-I/II EIAs (95% confidence interval [CI], 99.2%-100%); both EIAs have since been discontinued. This is comparable to the detection of 843 of 843 confirmed-positive samples during the ChLIA clinical trials (95% CI, 99.48%-100%). Incident HTLV infections occurred primarily among female repeat donors during 2008 throughout 2009., Conclusions: Donors testing falsely positive by historic EIAs since 1988 should be considered for reinstatement if a contemporary sample tests ChLIA nonreactive. Changes to the existing screening algorithm seem unlikely since new HTLV infections were detected among repeat donors., (© 2010 American Association of Blood Banks.)

Background: Nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) was introduced for blood donation screening in the United States in 1999. This study analyzes temporal trends of these two infections since NAT introduction., Study Design and Methods: Donation data from 1999 to 2008 were analyzed; each donation was tested for antibodies and viral RNA for HIV and HCV. Incidence for first-time (FT) donors was derived by multiplying that among repeat (RP) donors by the ratio of NAT yield rates between FT and RP donors. Incidence for all donors was the weighted mean based on percentage of FT and RP donors. Residual risk (RR) was determined using the window-period model., Results: During the 10-year period approximately 66 million donations were screened with 32 HIV (1:2 million) and 244 HCV (1:270,000) NAT yield donations identified. HCV prevalence among FT donors decreased by 53% for 2008 compared to 1999. HIV and HCV incidence among RP donors increased in 2007 through 2008 compared to 2005 through 2006. During 2007 through 2008, HIV incidence was 3.1 per 10(5) person-years (py), with an RR estimate of 0.68 per 10(6) (1:1,467,000) donations; HCV incidence was 5.1 per 10(5) py, with an RR estimate of 0.87 per 10(6) (1:1,149,000). The increase in HIV incidence was primarily among 16- to 19-year-old, male African American donors and that in HCV was primarily among Caucasian donors of 50 or more years. Donors from the Southern United States had higher incidence rates., Conclusion: HCV prevalence decreased significantly since NAT introduction. The increase in HIV and HCV incidence in 2007 through 2008 warrants continued monitoring and investigation.

Background: The number of apheresis collections increased significantly in recent years; however, data on viral marker rates among these collections are lacking., Study Design and Methods: Apheresis collection data for 2004 to 2008 were analyzed. All collections were tested for antibodies and viral RNA for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to human T-lymphotropic virus (anti-HTLV), and other markers. HBsAg-confirmed-positive but anti-HBc-nonreactive units were further verified by HBV DNA testing., Results: From 2004 to 2008, apheresis collections for double red blood cells (R2) increased by 294% to a total of 37% of all apheresis collections. Marker rates (/100,000) among all apheresis collections were 1.41, 7.83, 2.04, and 0.28, for HIV, HCV, HBsAg, and HTLV. Among R2 collections, rates (/100,000) were 6- to 13-fold higher than among non-R2 collections for HIV (3.50 vs. 0.53), HCV (21.84 vs. 1.96), and HBsAg (5.83 vs. 0.44), but not HTLV (0.53 vs. 018). First-time male R2 donors accounted for 25% to 100% of positivity but only 1% to 5% of the total number of apheresis collections. Incidence (/100,000 person-years) and residual risk estimates among repeat apheresis donors between 2007 and 2008 for HIV were 3.82 and 1:1.0 million, for HCV were 1.53 and 1:3.2 million, and for HBsAg were 4.85 and 1:200,000. These estimates were comparable to those among repeat whole blood donors., Conclusion: The risk of major blood-borne infections among current apheresis collections was low; however, an upward trend in the viral marker frequency among apheresis donations was attributable to the contribution of first-time, male R2 donors.

Background: Cytomegalovirus (CMV) transfusion-transmitted disease (TTD) remains a clinical concern. Universal leukoreduction has become one of the main strategies for the prevention of CMV-TTD. Through prospective clinical follow-up and testing of transfusion recipients (TRs), the risk for CMV-TTD was studied., Study Design and Methods: Transfused units were all leukoreduced and not prospectively screened for CMV. For TRs with negative baseline CMV testing results (CMV total antibody and DNA), all follow-up TR samples were tested for CMV total antibody and DNA, and retained linked donor serum samples were tested for CMV total antibody. In cases when CMV-TTD was suspected, donor sera were also tested for CMV DNA and selected TR samples were tested for CMV immunoglobulin M antibody. Evaluable transfusion was defined as a transfusion with TR sample(s) collected 14 to 180 days posttransfusion., Results: Forty-six TRs were negative for CMV at baseline. There were 1316 evaluable cellular blood transfusions to these TRs. Of 1316 evaluable cellular products, 460 (35%) were positive for CMV total antibody tested using linked donor samples. Three cases of probable CMV-TTD were found; however, there was no definitive proof from donor follow-up that they were transfusion associated., Conclusion: Among all 46 baseline seronegative recipients and 1316 evaluable transfusions, the calculated overall CMV-TTD risk was up to 6.5% (95% confidence interval [CI], 1.0%-18.0%) in terms of TRs and up to 0.23% (95% CI, 0.06%-0.62%) in terms of non-CMV-screened leukoreduced cellular products. In summary, after universal leukoreduction, CMV-TTD, while uncommon, may still occur.

Background: There have been few recent systematic studies of blood recipients for direct evidence of blood safety, especially for emerging pathogens that may pose a threat to the blood supply., Study Design and Methods: Recipients who would likely require transfusion from multiple donors were recruited and a blood specimen was collected before their first study transfusion and at intervals after their study transfusion(s). Blood samples associated with the units that were transfused to enrolled recipients were also collected. Part of each recipient specimen and selected donor specimens was tested for the targeted blood-borne agents, parvovirus B19 (B19) and Chlamydia pneumoniae (Cp), that were piloted in this study, and the remaining material was kept in a repository., Results: Between April 2004 and December 2006, a total of 120 recipients were recruited with 4047 subsequent donor exposures. On average, each recipient was followed up seven times. Of recipients who were adequately followed up and were initially immunoglobulin G antibody negative, one in 31 and one to two in 49 seroconverted to B19 and Cp after a total of 922 and 1413 evaluable transfusions, respectively. The detection of seroconversion was complicated by passively acquired donor antibodies for these two seroprevalent agents. Negative results for nucleic acids of the agents limited our ability to further clarify the relationship of these seroconversions to transfusion-transmitted infection., Conclusion: The risk of transfusion-associated B19 infection appears to be low but no conclusion of transfusion transmission can be made for Cp. The approach piloted through this study offers added value beyond the current hemovigilance strategy in the United States.

Background: Committed repeat donors are vital to the continued success of blood collections, yet the effect of age of first-time (FT) donation on return behavior is poorly described. Sixteen-year-old donors are increasingly allowed to donate and have the highest rates of adverse events, which negatively impacts return behavior., Study Design and Methods: Annual cohorts of allogeneic FT donors from 2005 and 2006 were selected within the American Red Cross system and followed for 25 and 13 months, respectively. Return and total yield rates among different age groups were compared., Results: A total of 2.3 million FT donors from 2005 and 2006 gave 4.2 million donations during the study. Sixteen- to 19-year old FT donors made up 41% of the FT donor base in 2005 and 16-, 17-, 18-, and 19-year-olds, respectively, had initial return rates of 62, 52, 35, and 28% and yield rates of 2.0, 1.76, 1.51, and 1.41 over 13 months. Multivariate analysis of FT yield rates shows that younger (16 and 17 years) and older (50+ years) donors, males, blood group O donors, and those without any initial adverse reaction are most likely to return. Increasing severity of donor adverse reactions correlated with a reduction in yield and return rates., Conclusion: FT 16-year-old donors had the highest return and yield rates despite the negative impact of increased adverse event rates. Donation at young age is critical to building a cadre of committed repeat donors but donor reactions must be addressed to ensure the donors' well-being and to sustain return behavior.

Background: This study used two approaches to estimate the current incidence of hepatitis B virus (HBV) in a US donor population., Methods: HBV incidence was estimated through the hepatitis B surface antigen (HBsAg) yield approach and the seroconversion method. Residual risk was estimated by the incidence–window period model. HBsAg yield refers to an HBsAg confirmed-positive, antibody against hepatitis B core antigen (anti-HBc)–nonreactive donation, adjusted for false-positive neutralization results. The number of HBsAg-seroconverting repeat donors divided by total number of person-years of evaluation or the HBsAg yield rate divided by HBsAg yield window gave rise to incidence estimates., Results: The seroconversion and the yield approach, respectively, gave an incidence estimate of 3.41 or 3.43 per 105 person-years. Using a revised infectious window period of 38 or 30 days for current HBsAg assays, the current residual risk for HBV was respectively estimated for 2006 to 2008 at 1 in 282,000 or 1 in 357,000 donations from the seroconversion approach and 1 in 280,000 or 1 in 355,000 donations from the yield approach. With the same database and methods, this is a decrease from 1 in 86,000 to 1 in 110,000 observed in 1997 to 1999., Conclusions: Current HBV incidence and residual risk are lower than earlier estimates, especially in the youngest donors, but remain higher in the absence of HBV nucleic acid test than those for human immunodeficiency virus or hepatitis C virus (HCV). In addition to the exclusion of HBsAg false-positive donors, the reduction could reflect shortened window periods and decreased incidence rates due to vaccination or other reasons.

Background: Since 2004, several reported transfusion transmissions of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom have reawakened concerns about the possible risk of similar transmissions of nonvariant or classic forms of CJD., Study Design and Methods: Patients with a CJD diagnosis and a history of donating blood were reported to the study coordinator. Through review of blood distribution and hospital records, the recipients of blood components from these donors were identified. We then determined each recipient's vital status and, if deceased, the cause(s) of death identified by matching the recipient's personal identifiers with the Centers for Disease Control and Prevention's National Death Index database. We conducted such searches after recipients were enrolled in this study and annually thereafter for those who remained alive., Results: The study included a total of 36 blood donors who subsequently developed CJD and 436 recipients. Through 2006, 91 of these recipients were still alive, 329 were deceased, and 16 were lost to follow-up. After transfusion, these three groups had survived a total of 2096.0 person-years. A total of 144 recipients survived 5 years or longer after transfusion and 68 of them had received blood donated 60 or fewer months before the onset of CJD in the donor. We identified no recipient with CJD., Conclusions: The current results of this large, ongoing lookback study show no evidence of transfusion transmission of CJD. They reinforce the conclusion that the risk, if any, of transfusion transmission of prion disease by CJD donors is significantly lower than the comparable risk of such transmission by vCJD donors.

Background: Serologic screening for syphilis has been justified in part as a surrogate marker for infections caused by other pathogens such as human immunodeficiency virus (HIV). This study assessed the current surrogate value of the test., Study Design and Methods: Testing results for blood donors with the American Red Cross Blood Services between January 1, 2006, and December 31, 2007, were analyzed. All donations were tested according to standard procedures for markers of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), syphilis, and other infections. The frequency of window-period (w-p) infections interdicted by syphilis testing was estimated., Results: There were significantly higher frequencies of HIV, HCV, hepatitis B surface antigen (HBsAg), and HTLV confirmed-positive donations among those with positive syphilis test results, although the sensitivity of syphilis test positivity in these groups was low. Among more than 3 million repeat donors with complete testing through reactive donation confirmation for both syphilis and HIV (anti-HIV and HIV RNA), 225 seroconverted for syphilis but not for anti-HIV or HIV RNA and 83 converted for HIV (anti-HIV or HIV RNA) but not for syphilis, with only 1 who converted for both syphilis and HIV, resulting in an incidence ratio of 150 (95% confidence interval, 21-1080) and a sensitivity of 1.2 percent. No syphilis seroconverters converted for HCV, HBsAg, or anti-HTLV., Conclusion: Syphilis testing presents no surrogate value for incident HCV, HBV, and HTLV infections and could only remove approximately 1 HIV w-p unit of every 148 million donations.

Background: A large number of blood donors are deferred each year and many of the temporarily deferred donors do not return to donate blood. This study analyzed actual deferral and return donation data from the American Red Cross to further assess the impact of donor deferral on donor availability., Study Design and Methods: Voluntary blood donors who presented between 2001 and 2006 were included in this study. Deferred donors were classified into three groups according to their history of presentation during the prior 2 years: Group 1 with no prior donation or deferral, Group 2 with prior donation but no deferral, and Group 3 with prior deferral. Temporarily deferred donors in Groups 1 and 2 who did not return during the next 3 years were considered lost donors. All indefinitely deferred donors were lost donors., Results: A mean of 12.8 percent of a total of 47,814,370 donor presentations between 2001 and 2006 resulted in a deferral. While majority of the deferrals were related to donor safety reasons, deferrals for recipient safety reasons accounted for 22.6 percent of deferrals or 2.9 percent of total presentations. Temporary and indefinite deferrals for recipient safety-related reasons collectively caused an estimated loss of 647,828 donors during the 6 years. An additional 1,042,743 donors were lost due to deferrals for donor safety-related reasons during the same period., Conclusions: The results on donor loss after deferral call attention to the impact of donor deferrals on donor availability and the need to monitor and assess the necessity and effectiveness of such deferrals.

Background: In certain circumstances, there is no method for estimating incidence based on testing results on a single blood sample from first-time blood donors, severely limiting the ability to assess the residual risk of blood-borne infections among this donor subpopulation., Study Design and Methods: Incidence rates were estimated for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) among first-time donors using the formula (P(2) - P(1))/D, where P(1) is the prevalence among blood donations from first-time donors of the minimum eligible ages for donation, P(2) is the prevalence among donations from first-time donors of an older age group, and D is the age difference (in years) between the older and younger donor groups., Results: Estimating incidence among first-time donors using the proposed method based on a single test for anti-HCV produced similar results to those based on HCV nucleic acid test (NAT) yield cases, by sex and in different periods. Comparison of the proposed method with HIV NAT yield also showed similar results although the small number of HIV NAT yield cases limits interpretation., Conclusions: The proposed method provides an alternative way for estimating incidence of certain blood-borne infections among first-time donors, provided that our assumptions are met. It helps residual risk assessment in donor populations where first-time donors account for most of the donations and only one test result is available for each donor.

Background: Maintaining a stable blood supply is a critical goal of the American Red Cross Blood Services. Extensive Red Cross data provided the opportunity to assess both long-term and short-term trends in the variation of weekly blood donations., Study Design and Methods: Overall trends and week-to-week variation in donation rates were assessed in volunteer, whole-blood donations from 1995 to 2005 among three Red Cross donor regions: the Connecticut region, the Greater Chesapeake and Potomac (Maryland) region, and the Southern California region, adjusting for population change, calendar time, age, sex, and donor region., Results: Weekly donation rates varied widely by region, ranging from 3.5 donations per 10,000 persons in Southern California to 10.2 donations per 10,000 in Connecticut. Week-to-week variation in donation rates within each region was also quite high. Typical swings in weekly donation rates ranged from 38 percent in Connecticut to 56 percent in Southern California. Week-to-week variation was also 103 percent higher (95% confidence interval [CI], 87%-120%) among 18- to 24-year-old donors, compared to 25- to 44-year-olds, ranging from 32 to 49 percent. By comparison, week-to-week variation among adults 25 and older was more stable, ranging from 16 to 21 percent., Conclusion: This study suggests that there is a great deal of variation in donation rates, particularly among the youngest donors. Improving recruitment and retention among these donors will be critical to maintaining an adequate blood supply as the donor population ages.

Background: The American Red Cross has been maintaining a research database of all blood donors. Such a database provides a unique opportunity for monitoring changes over time in donor and donation patterns., Study Design and Methods: Changes in age distribution among blood donors were analyzed through comparison of the volunteer donor population in 1996, 1999, 2002, and 2005, before and after adjustment for demographic changes of the general population in the United States., Results: Donations by repeat donors 50 years or older as a proportion of total donations increased from 22.1 percent in 1996 to 34.5 percent in 2005, or 1.4 percent per year, whereas donations from repeat donors of 25 to 49 years decreased from 49.1 percent in 1996 to 37.1 percent in 2005, or 1.3 percent per year. After adjusting for general population trends, the effective number of donors decreased by more than 10 percent in female and male repeat donors of age 20 to 49 years and male first-time donors of age 25 to 49 years from 1996 to 2005; female and male repeat donors of age 25 to 39 years decreased by greater than 40 percent. Prevalence rates of major infectious disease markers decreased by 3.3 percent or more per year for first-time donations and by 6.4 percent or more per year for repeat donations., Conclusion: The aging patterns of blood donors suggest the need for improved recruitment and retention in the young adult and middle-aged groups. A severe shortage of blood and blood components may be forecast in the foreseeable future unless offset by significant increased supply or reduced usage of blood and blood components.

Background: Donor deferral registries (DDRs) detect repeat donations by previously deferred donors and prevent their release. The utility of DDRs has not been objectively demonstrated., Study Design and Methods: A total of 10.2 million first-time donors to the American Red Cross from 1995 through 2002 were reviewed to identify donors deferred by screening tests for human immunodeficiency virus (HIV; 0.19% of donors), hepatitis C virus (HCV; 0.55%), and hepatitis B virus (HBV; 0.13%). All repeat-reactive (RR) donors were deferred despite confirmatory testing. Donors were notified and counseled about their test results and deferral. Their subsequent donation behavior was assessed., Results: A total of 414 HIV-deferred donors (2.1%), 471 HCV-deferred donors (0.8%, p < 0.001 vs. HIV and HBV), and 222 HBV-deferred donors (1.6%, p < 0.01 vs. HIV) returned to donate despite their deferred status. For all three tests, confirmed-positive donors were less likely to return. Of donors originally confirmed positive, only 7 returning donors were negative by screening (thus the repeat donation interdicted from distribution by the DDR): 0 HIV RR donors, 2 of 36,092 HCV RR donors, and 5 of 8,404 HBV RR donors. Review of the laboratory results for the HCV donors and one HBV donor was consistent with originally false-positive confirmation tests. The four other HBV confirmed-positive donors were anti-hepatitis B core antigen-positive on their subsequent donation, which was discarded despite the DDR., Conclusion: Of 10.2 million donors, the DDR did not prevent the release of any potentially dangerous blood component due to inappropriate return of donors deferred for HIV, HCV, and HBV tests. The effectiveness of DDRs should be evaluated for other deferrals.

Background: The Uniform Donor History Questionnaire (UDHQ) was implemented across the American Red Cross Blood Services in 2005. This study assessed the potential impact of changes inherent in UDHQ implementation on deferral and on prevalence of infectious disease markers among donated units., Study Design and Methods: Deferral and donation records were extracted and analyzed for the period of April 1, 2005, to September 30, 2005, after the implementation of the UDHQ and for the same period in the previous year. For comparison, most of the questions in the UDHQ were aligned with corresponding questions in the previous questionnaire, although such alignment could not be exact because of changes in the wording and organization of the questions., Results: From 2004 (1 year previously) to 2005 (UDHQ), significant changes in deferral rate were observed for different groups of deferral questions, with the largest being +99.2 percent for "man who had sex with another man" and +92.0 percent for "receipt of blood, tissue, organ, or clotting factor concentrates or a bleeding condition or a blood disease" among repeat presenters. Changes to the educational material and the wording of questions, elimination of compound questions, and other concurrent changes could have contributed to the changed deferral rates. There was no significant change in prevalence rates of major infectious disease markers., Conclusions: Implementation of the UDHQ impacted on donor deferral, including increased deferral among repeat presenters. No significant impact was observed for infectious disease marker rates. Further monitoring for longer-term trends is recommended.

Background: Health history questions identify blood donors believed to pose a higher risk of transmission of infectious diseases. This study assesses the current impact of some of these questions on blood safety as reflected by infectious disease markers., Study Design and Methods: Donors who were deferred from donating blood due to health history question(s) were recruited at four different regions of the American Red Cross Blood Services. A blood sample was tested for serologic markers of blood-borne infections as performed for accepted blood donors., Results: Of 497 deferred donors enrolled, 29 donors were deferred for having had "yellow jaundice, liver disease, or hepatitis since the age of 11" (Question 3), 1 of whom had hepatitis C virus antibodies (anti-HCV) and hepatitis B core antigen antibodies (anti-HBc), 2 had anti-HBc, and 1 had anti-HCV (p < 0.05 for both markers). Among 37 donors deferred for having "ever tested positive for hepatitis" (Question 4), 1 had hepatitis B surface antigen and anti-HBc and 3 had anti-HBc (p < 0.05 for both markers). Of 14 donors deferred for "having ever used a needle, even once, to take any illegal or nonprescription drug" (Question 12), 1 had anti-HCV, human T-lymphotropic virus-I antibodies and anti-HBc, 1 had anti-HCV and anti-HBc, and 2 had anti-HCV (p < 0.05 for all three markers)., Conclusions: Blood donors deferred for standard blood donor questions regarding risk of viral hepatitis as well as those with a history of intravenous drug use were more likely to have higher hepatitis marker rates than those who were not deferred. No significant findings were identified for other markers or questions.

Background: Health history questions are introduced into the predonation interview to identify blood donors believed to pose a higher risk of infectious diseases to recipients. This study assesses the current impact of some of those questions., Study Design and Methods: Donor deferral and donation data were extracted from a research database of the American Red Cross. The prevalence of hepatitis B surface antigen or antibodies to human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus was obtained for different groups of donors who were temporarily deferred in 2000 through 2001 and later returned to donate blood in 2000 through 2003. The results were compared with either first-time or repeat donors in 2000 through 2003, while controlling for differences in sex, age, and year of donation., Results: Of donors temporarily deferred in 2000 through 2001 who had had no donation or deferral during the previous 2 years, only 22.08 percent subsequently returned to donate blood in 2000 through 2003. Donations from returning donors who had been deferred for potential infectious disease risk did not show a higher prevalence for any of the viral markers when those with no donation or deferral during the previous two years were compared with first-time donations, and those with prior donation were compared with repeat donations., Conclusion: Blood donors temporarily deferred in 2000 through 2001 for potential risk of viral infection who later returned to donate blood did not appear to pose a higher risk compared to first-time or repeat donors. The effectiveness of some of the currently used deferral questions in reducing viral risks warrants further study.

Background: The American Red Cross has been maintaining a research database of all blood donations, including all testing results for infectious disease markers, since 1995. This study analyzes the temporal trends of major blood-borne infections among blood donors., Study Design and Methods: Temporal trends for age- and sex-specific prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis infections in US blood donors were analyzed based on linear trend or time series model or other models as appropriate., Results: From 1995 to 2002, significant declines have been observed for infections that used to be at relatively higher levels. Declines in prevalence were slower among first-time donations than repeat donations. There was an increase in prevalence of anti-HCV among first-time male donors of 50 to 59 years of age. Anti-HIV prevalence appeared to have increased among first-time male donors of 30 to 39 years of age since 2000., Conclusion: Different sex and age groups showed various patterns of decline and even signs of increase. The increasing prevalence among some age and sex groups may merit further investigation.