Modeling US blood donor deferrals under a policy of individual risk assessment for HIV risk sexual behavior.

BACKGROUND: In May 2023, the Food and Drug Administration (FDA) released final guidance for blood donor eligibility that recommended the elimination of 3-month deferral for men who have sex with men (MSM) and the related deferral for women who have sex with MSM. In its place, FDA introduced an individual risk assessment policy of asking all presenting blood donors, regardless of sex or gender, if they have had a new partner or more than one sexual partner in the last 3 months and deferring those who also report anal sex (penile-anal intercourse) during this period. We modeled the possible impact of this policy on the US blood donor base. STUDY DESIGN AND METHODS: We developed a computational model to estimate the percentage of blood donors who would be deferred under a policy of individual HIV risk assessment. The model incorporated demographic information about donors and national survey data on HIV risk behaviors and included age and sex distributions and dependencies. RESULTS: Our model estimates that approximately 1.2% of US blood donors would be deferred under the individual HIV risk assessment paradigm. DISCUSSION: The model predicts a relatively minor effect of replacing the time-based deferral for MSM with individual risk-based deferral for sexual behavior. As US blood centers implement this new policy, the effect may be mitigated by donor gains, which warrant further study. The new policy is unlikely to adversely affect the availability of blood and blood components.

Posttransfusion Sepsis Attributable to Bacterial Contamination in Platelet Collection Set Manufacturing Facility, United States.

During May 2018‒December 2022, we reviewed transfusion-transmitted sepsis cases in the United States attributable to polymicrobial contaminated apheresis platelet components, including Acinetobacter calcoaceticus‒baumannii complex or Staphylococcus saprophyticus isolated from patients and components. Transfused platelet components underwent bacterial risk control strategies (primary culture, pathogen reduction or primary culture, and secondary rapid test) before transfusion. Environmental samples were collected from a platelet collection set manufacturing facility. Seven sepsis cases from 6 platelet donations from 6 different donors were identified in patients from 6 states; 3 patients died. Cultures identified Acinetobacter calcoaceticus‒baumannii complex in 6 patients and 6 transfused platelets, S. saprophyticus in 4 patients and 4 transfused platelets. Whole-genome sequencing showed environmental isolates from the manufacturer were closely related genetically to patient and platelet isolates, indicating the manufacturer was the most probable source of recurrent polymicrobial contamination. Clinicians should maintain awareness of possible transfusion-transmitted sepsis even when using bacterial risk control strategies.

An outbreak of anaphylactic transfusion reactions to group B plasma and platelets and its possible relationship to Alpha-Gal syndrome.

BACKGROUND: Alpha-gal syndrome (AGS) is a potentially life-threatening acquired meat allergy associated with tick bites. The allergen Galactose-α-1,3-Galactose is antigenically similar to the B blood group antigen. B blood group status offers some protection against development of the allergy. Although not preferred practice, transfusion of plasma and platelets from group B donors is believed to be safe for group O recipients. STUDY DESIGN AND METHODS: Anaphylactic transfusion reactions were reported for three patients in two Washington DC hospitals from Nov 2022 to February 2023. A chart review was performed for all three patients. Patients or family members were interviewed, and IgE levels to alpha-gal were measured in two of the three patients. RESULTS: One reaction was acutely fatal. All reactions were to blood group B Plasma or Platelets in blood group O recipients. One patient had two prior anaphylactic reactions to group O RBCs and group B Plasma in a previous admission. All patients came from southern Maryland where AGS is an emerging problem. Two patients had histories of tick bites, previously unexplained gastrointestinal complaints, and abnormal elevated levels of IgE to alpha gal. Two patients had cat allergies. DISCUSSION: AGS is an emerging problem which may have implications for blood transfusion practice. Avoidance of blood group B antigen containing components may be prudent in non-blood group B patients with established AGS. Investigation for AGS should be considered in the evaluation of anaphylactic transfusion reactions.

HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.

BACKGROUND: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

Effectiveness of the post-donation instruction sheet in conveying information to repeat blood donors.

BACKGROUND AND OBJECTIVES: Written materials are commonly used for blood donor education. While pre-donation materials are largely standardized across US blood collectors, the post-donation instruction sheet (PDIS) is variable and few have been evaluated to assess their effectiveness in conveying information as reflected by donors' attention, understanding and recall. METHODS: An online survey was sent to two independent randomly selected samples of repeat donors, before and after implementation of the enhanced PDIS. RESULTS: A total of 12 935 blood donors responded (33·4% response rate). Most donors did not read the entire PDIS - 34·3% less than half and 18·1% none. Of the 10 593 donors who reported reading any of the PDIS, 97·8% recalled instructions about immediate post-donation care (e.g. extra fluids/no exercise) and 88·0% to call with questions/problems. However, only 50·1% remembered reading about what to do if you felt dizzy/faint and 32·4% about care for bruises. Recall rates in every area were similar before and after revision; except after revision, more donors remembered seeing information about maintaining iron and fewer that you should call the centre back with additional health information (P < 0·0001). DISCUSSION: Blood collectors rely heavily on written materials to convey instructions to donors. Most repeat donors do not read the entire PDIS, and many do not recall important information. More donors recalled seeing how to maintain iron with the enhanced PDIS, but recall deficits remained on how to care for adverse reactions. Written materials alone appear to be insufficient to educate some donors about new or updated topics.

Trend in ABO-incompatible RBC transfusion-related fatalities reported to the FDA, 2000-2019.

BACKGROUND: ABO-incompatible red blood cell (RBC) transfusions and acute hemolytic reactions occur infrequently, yet resultant fatalities are reported to the US Food and Drug Administration (FDA) every year. We describe a 20-year retrospective study of reported mistransfusion cases to identify temporal trends, common causes, and corrective actions taken to prevent recurrence. STUDY DESIGN AND METHODS: ABO-incompatible RBC transfusion-related fatalities reported to the FDA in 2000-2019 were reviewed for patient demographics, primary attributed cause, contributing factors, and corrective actions. RESULTS: Eighty reported deaths after ABO-incompatible RBC transfusion occurred in the 20-year period. A decrease in the number of cases after 2008 was sustained through 2019 (mean 6 cases/y, 2000-2009 vs 2 cases/y, 2010-2019). The estimated rate of reported mistransfusion fatalities was 1 per 2 million RBC units transfused in 2000-2009 and 1 per 7.14 million RBC units in 2010-2019 (P < .0001). Administration errors (wrong patient or wrong unit transfused) and sample collection errors (wrong blood in tube [WBIT]) significantly decreased over time but remained the most common causes. In all WBIT cases, verification of patients' ABO type with a second sample or historical type was not performed before transfusion; 16 of 19 (84%) institutions that reported corrective actions subsequently instituted this requirement. In the other categories, 22 of 58 (38%) facilities reported plans for technological process improvements, such as electronic patient identification. CONCLUSIONS: The rate of reported fatalities from ABO-incompatible RBC transfusion has significantly decreased in the past decade. Still, about two cases are reported each year, highlighting gaps in best practices and areas for improvement.

Predictive model for Zika virus RNA minipool nucleic acid testing in outbreak scenarios.

BACKGROUND: Zika virus (ZIKV), a mosquito-borne flavivirus, causes asymptomatic infections in blood donors and can be transmitted by transfusion. During the 2016 US outbreak, universal individual-donation nucleic acid testing (ID-NAT) was used to screen the blood supply for ZIKV. Testing pooled samples from multiple donations with minipool (MP)-NAT is less sensitive than ID-NAT, which raised questions about its utility in ZIKV outbreaks. STUDY DESIGN AND METHODS: A mathematical model and computer simulation determined the risk of missing ID-NAT-reactive and immunoglobulin (Ig) M-negative donations in a ZIKV outbreak if MP-NAT is used initially instead of ID-NAT. The model calculated the time required for ZIKV RNA to replicate to a concentration detectable by testing donations individually or in pools of 6 (MP6) or 16 (MP16). A computer simulation then randomly selected infection times to determine the probability of detection by the candidate tests. RESULTS: The probability of detecting the first ID-NAT-reactive unit in an outbreak is 92% (2.5th-97.5th percentile, 79%-99%) by MP6 and 85% (2.5th-97.5th percentile, 67%-99%) by MP16. When one donation is detected by MP-NAT, the model predicts that the chance of having missed one or more ID-NAT-reactive donations is 8% to 15%. The probability of missing a unit by MP-NAT is constant over the course of the outbreak (8% by MP6, 15% by MP16). CONCLUSION: The model predicts that the probability that a candidate MP-NAT will detect the first ID-NAT-reactive unit in a ZIKV outbreak is 85% to 92% and remains constant over time.

The effect of iron balance on platelet counts in blood donors.

BACKGROUND: Thrombocytosis (or, less commonly, thrombocytopenia) is associated with iron-deficiency anemia and resolves with iron therapy. Many volunteer blood donors have low iron stores, with or without anemia. Iron balance could affect platelet counts in blood donors. STUDY DESIGN AND METHODS: Whole blood donors deferred for finger-stick hemoglobin levels less than 12.5 g/dL were evaluated by complete blood count and serum iron panel before and after oral iron treatment. Group assignment for iron depletion was based on serum ferritin cutoffs of less than 20 µg/L for women and less than 30 µg/L for men or was based on changes in serum ferritin levels after iron replacement. RESULTS: Among 1273 Hb-deferred whole blood donors, 55% (619 of 1128) of the women and 70% (102 of 145) of the men were iron depleted. Iron-depleted donors had higher platelet counts compared with donors who had normal ferritin levels (women: 286 vs. 268 × 103 /µL; p < 0.0001; men: 246 vs. 222 × 103 /µL; p = 0.0454). Only 4.4% of iron-depleted donors had thrombocytosis (> 400 × 103 /µL) compared with 2.0% of donors who had normal ferritin levels (p = 0.017). Iron replacement decreased platelet counts in iron-depleted female donors (mean, -19,800/µL; interquartile range, 8000 to -45,000/µL), but not in donors who had normal or stable ferritin levels. The same trends were observed in male donors. CONCLUSION: Iron-depleted donors had higher platelet counts than donors who had adequate iron stores. Oral iron replacement decreased platelet counts on average by about 20,000/µL in iron-depleted donors but had no effect on platelet counts in donors who had normal or stable ferritin levels.

Autologous lymphapheresis for the production of chimeric antigen receptor T cells.

BACKGROUND: The first step in manufacturing chimeric antigen receptor (CAR) T cells is to collect autologous CD3+ lymphocytes by apheresis. Patients, however, often have leukopenia or have other disease-related complications. We evaluated the feasibility of collecting adequate numbers of CD3+ cells, risk factors for inadequate collections, and the rate of adverse events. STUDY DESIGN AND METHODS: Apheresis lymphocyte collections from patients participating in three CAR T-cell clinical trials were reviewed. Collections were performed on the COBE Spectra by experienced nurses, with the goal of obtaining a minimum of 0.6 × 109 and a target of 2 × 109 CD3+ cells. Preapheresis peripheral blood counts, apheresis parameters, and product cell counts were analyzed. RESULTS: Of the 71 collections, 69 (97%) achieved the minimum and 55 (77%) achieved the target. Before apheresis, the 16 patients with yields below the target had significantly lower proportions and absolute numbers of circulating lymphocytes and CD3+ lymphocytes and higher proportions of circulating blasts and NK cells than those who achieved the target (470 × 106 lymphocytes/L vs. 1340 × 106 lymphocytes/L, p = 0.008; 349 × 106 CD3+ cells/L vs. 914 × 106 CD3+ cells/L, p = 0.001; 17.6% blasts vs. 4.55% blasts, p = 0.029). Enrichment of blasts in the product compared to the peripheral blood occurred in four patients, including the two patients whose collections did not yield the minimum number of CD3+ cells. Apheresis complications occurred in 11 patients (15%) and, with one exception, were easily managed in the apheresis clinic. CONCLUSIONS: In most patients undergoing CAR T-cell therapy, leukapheresis is well tolerated, and adequate numbers of CD3+ lymphocytes are collected.

Apheresis technology correlates with bacterial contamination of platelets and reported septic transfusion reactions.

BACKGROUND: Apheresis technology to collect platelet (PLT) components differs among devices. We evaluated the relationship of the plateletpheresis device with bacterial contamination and reported septic transfusion reactions. STUDY DESIGN AND METHODS: Plateletpheresis was performed using Amicus (Fenwal, a Fresenius Kabi Company) or Trima (Trima Accel, TerumoBCT) from 2010 to 2014. All donations used inlet-line sample diversion and were tested by quality control (QC; Day 1) aerobic culture. Rates of bacterial contamination and septic reactions to PLTs were calculated for both devices. RESULTS: During the 5-year study period, plateletpheresis collections using Amicus and Trima devices totaled 1,486,888 and 671,955 donations, respectively. The rate of confirmed-positive bacterial cultures of apheresis PLT donations was significantly higher with Amicus than with Trima (252 vs. 112 per 106 donations [odds ratio {OR}, 2.3; 95% confidence interval {CI}, 1.8-2.9]). Septic transfusion reactions were caused by 30 apheresis PLT units from 25 contaminated Amicus procedures and three apheresis PLT units from three contaminated Trima procedures. The overall rate of septic reactions was significantly higher with apheresis PLT components collected with Amicus than with Trima (16.8 vs. 4.5 per 106 donations [OR, 3.8; 95% CI, 1.1-12.5]). All apheresis PLT components implicated in septic transfusion reactions had negative QC culture results incubated through Day 5 (i.e., false negatives). CONCLUSION: Apheresis technology affects bacterial contamination of plateletpheresis collections. The device-specific, higher rate of confirmed-positive bacterial culture results also correlated with a significantly higher rate of reported septic transfusion reactions to apheresis PLTs.

Predicted effect of selectively testing female donors for HLA antibodies to mitigate transfusion-related acute lung injury risk from apheresis platelets.

BACKGROUND: The use of male-donor-predominant plasma has reduced the risk of transfusion-related acute lung injury (TRALI), but the possible benefit of different mitigation strategies for other components is unknown. We evaluated the risk of TRALI from apheresis platelets (PLTs) to predict the effect of selectively testing female plateletpheresis donors who have been pregnant for HLA antibodies. STUDY DESIGN AND METHODS: The American Red Cross hemovigilance program classified TRALI cases from apheresis PLTs or red blood cells (RBCs) in 2006 to 2013 or from predominantly male-donor (>95%) plasma in 2008 to 2013 and compared the component-specific TRALI rates. RESULTS: The overall rate of TRALI was significantly higher for apheresis PLTs (6.2 cases per 10(6) units; OR [95% CI], 3.3 [2.3-4.8]) or plasma (3.8 cases per 10(6) units; OR [95% CI], 2.0 [1.4-2.9]) compared to RBCs (1.9 per 10(6) units). Twenty-nine of the 41 apheresis PLT cases involved female donors; 28 had been pregnant, and one had not been pregnant and was not tested. Twenty-five (61%) of the apheresis PLT TRALI cases had female donors with HLA Class I or Class II antibodies. In five of six cases that implicated specific HNA antibodies, the female parous donors also had multiple HLA antibodies. CONCLUSIONS: TRALI was more likely after transfusion of apheresis PLTs than male-donor-predominant plasma or RBCs. A selective strategy to test all female plateletpheresis donors who have been pregnant for HLA antibodies might reduce the risk of TRALI by approximately 60% and prevent some cases from coexisting HNA antibodies.

2015 proceedings of the National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium.

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.

Clostridium perfringens in apheresis platelets: an unusual contaminant underscores the importance of clinical vigilance for septic transfusion reactions (CME).

BACKGROUND: Posttransfusion sepsis is typically caused by aerobic bacteria in apheresis platelets (PLTs) that escape detection by routine quality control cultures performed on every donation before components are distributed. We report the first case to implicate an anaerobic isolate, Clostridium perfringens, in apheresis PLTs and investigate its detection in vitro by approved tests. STUDY DESIGN AND METHODS: The C. perfringens strain was inoculated at high (10-100 colony-forming units [CFUs]/mL) or low (1-10 CFUs/mL) concentrations into apheresis PLTs and evaluated for growth over 5 to 7 days by qualitative plate cultures, culture-based assays (BacT/ALERT 3D), and rapid (PLT PGD) tests. RESULTS: C. perfringens grew in only 3 of 8 apheresis PLT units after inoculation at either high (2 units) or low (1 unit) concentrations. The PGD test detected the isolate after 5 days in 1 unit with 4.7 × 10(5) CFUs/mL but failed at five other time points in units with greater than 10(5) CFUs/mL. CONCLUSION: C. perfringens demonstrated variable growth in spiked PLTs and was not consistently detected by a rapid test even when high levels of contamination were present. The case underscores the importance of direct observation during transfusion, appropriate clinical management, and immediate reporting of suspected septic reactions to the blood center.

An international survey of pediatric apheresis practice.

INTRODUCTION: Pediatric apheresis (PA) has distinct characteristics compared to adult apheresis, and requires specialized knowledge and experience to perform safely, particularly in low-weight patients. As evidence-based medicine advances the field of therapeutic apheresis, increased attention must be paid to pediatric patients with conditions for which apheresis is indicated. METHODS: An electronic survey of >5,000 potential participants throughout the world was conducted to ascertain the scope and the current state of practice. RESULTS: The survey elicited 159 responses from 12 countries; 107 of the responses provided sufficient information for analysis. Participants performed an average of 176 PA procedures/year (range: 1-2,000). The types of PA procedures were therapeutic plasma exchange (92% of centers), red cell exchange (86%), leukocyte depletion (87%) and peripheral blood hematopoietic progenitor cell collection (72%). More than 65% of the centers had treated children older than 5 years with PA. Many centers had also performed PA on younger children; 40% have treated patients <12 months of age; 61% had treated patients 1-5 years old. 36% of centers reported that they would perform apheresis regardless of patient weight; 18% used a 5 kg threshold, 11% used 5-10 kg, and 17% used 10 kg as their weight threshold. CONCLUSION: This report is the largest single survey of centers performing PA. The results provide information about the scope and diversity of PA and identify areas where considerable variability in practice exists. Further exploration of these differences could establish best practices in PA through international research and collaboration.

How we manage AB plasma inventory in the blood center and transfusion service.

The growing use of group AB plasma in the United States in recent years poses unique challenges to blood centers and transfusion services. Blood centers must collect sufficient plasma components from a limited pool of group AB donors while taking steps to improve transfusion safety that further restricts the available supply. Transfusion services, on the other hand, must use the finite resource in the most conscientious and medically appropriate manner. Recently, many investigations have challenged long-held beliefs about transfusion practice and appropriate indications for blood components across a variety of specialties. Balancing supply and demand of group AB plasma requires collaboration between blood suppliers and transfusion services, and opportunities for improvement exist on both sides of the equation.

A comparison of human immunodeficiency virus, hepatitis C virus, hepatitis B virus, and human T-lymphotropic virus marker rates for directed versus volunteer blood donations to the American Red Cross during 2005 to 2010.

BACKGROUND: At most US blood centers, patients may still opt to choose specific donors to give blood for their anticipated transfusion needs. However, there is little evidence of improved safety with directed donation when compared to volunteer donation. STUDY DESIGN AND METHODS: The percentage of directed donations made to the American Red Cross (ARC) from 1995 to 2010 was determined. Infectious disease marker rates for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), and human T-lymphotropic virus (HTLV) were calculated for volunteer and directed donations made from 2005 to 2010. Odds ratios (ORs) were calculated to compare marker-positive rates of directed donations to volunteer donations. RESULTS: The percentage of donations from directed donors declined from 1.6% in 1995 to 0.12% in 2010. From 2005 to 2010, the ARC collected 38,894,782 volunteer and 69,869 directed donations. Rates of HIV, HCV, HBV, and HTLV for volunteer donations were 2.9, 32.2, 12.4, and 2.5 per 100,000 donations, respectively; for directed, the rates were 7.2, 93.0, 40.1, and 18.6 per 100,000. After demographics and first-time or repeat status were adjusted for, corresponding ORs of viral marker positivity in directed versus volunteer donations were not significant for HIV, HBV, or HTLV and significant for HCV (OR, 0.7; 95% confidence interval, 0.50-0.90). CONCLUSIONS: Directed donations have declined by 92% at the ARC since 1995, but have higher viral marker rates than volunteer donations. The difference can be explained in part by the effects of first-time or repeat status of the donors. Patients considering directed donation should be appropriately counseled about the potential risks.

The residual risk of transfusion-related acute lung injury at the American Red Cross (2008-2011): limitations of a predominantly male-donor plasma mitigation strategy.

BACKGROUND: The American Red Cross began preferentially distributing plasma from male donors in 2007 and subsequently observed an 80% decrease in reported cases of transfusion-related acute lung injury (TRALI) after plasma transfusion. Plasma distributions from male donors now exceed 99% for groups A, B, and O, but only approximately 60% for group AB. We evaluated the ongoing risk of TRALI and the ABO blood group of involved plasma donors. STUDY DESIGN AND METHODS: The rate of suspected TRALI per distributed components before (2006) and after (2008-2011) implementing the predominantly male-donor plasma strategy is compared. RESULTS: The risk of TRALI from the general inventory of distributed plasma decreased significantly from 18.6 cases per million units in 2006 to 4.2 cases per million units in 2008 to 2011 (p < 0.0001). However, the risk from AB plasma did not change (26.3 cases per million units) and was significantly greater than group A, B, and O plasma in 2008 to 2011 (1.8 per million units; odds ratio 14.5; 95% confidence interval, 6.8-30.9). Group AB plasma from female donors with HLA or HNA antibodies accounted for 14 of 28 (50%) of TRALI cases but less than 4% of all plasma units distributed in 2008 to 2011. CONCLUSION: The risk of TRALI after plasma transfusion has been markedly reduced for blood groups A, B, and O but not for AB, reflecting continued reliance on group AB plasma from female donors to meet increasing demand.

Current efforts to reduce the risk of syncope among young blood donors.

PURPOSE OF REVIEW: This review examines recent research on syncope after whole blood donation and efforts by blood centers to improve safety for young blood donors. RECENT FINDINGS: Young (16-18-year-old) volunteers contribute about 14% of the whole blood collected by the American Red Cross each year. Although quite safe, blood donation has some attendant risk, and syncopal reactions are more common among the youngest donors. Precautionary measures include predonation education, environmental controls, water ingestion shortly before phlebotomy, and distraction and muscle tension during collection. American Red Cross and Blood Systems, Inc. introduced new criteria to select donors with an estimated blood volume above 3.5 l. The changes led to about a 20% decrease in reactions among young blood donors, with the greatest benefit observed among the youngest, most susceptible donors. SUMMARY: Although the risk to blood donors cannot be eliminated, a systematic approach can achieve a significant and sustained improvement among vulnerable donor populations. Further research should explore novel ways to reduce the risk of syncope and prevent the uncommon, but potentially serious, associated injuries after whole blood donation.