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Background: Washing red blood cell (RBC) units mitigates severe allergic transfusion reactions. However, washing reduces the time to expiration and the effective dose. Automated washing is time- and labor-intensive. A shortage of cell processor tubing sets prompted review of medical necessity for washed RBC for patients previously thought to require washing., Study Design and Methods: A single-center, retrospective study investigated discontinuing wash RBC protocols in chronically transfused adults. In select patients with prior requirements for washing, due to a history of allergic transfusion reactions, trials of unwashed transfusions were performed. Patient demographic, clinical, laboratory, and transfusion data were compiled. The per-unit washing cost was the sum of the tubing set, saline, and technical labor costs., Results: Fifteen patients (median age 34 years interquartile range [IQR] 23-53 years, 46.7% female) were evaluated. These patients had been transfused with a median of 531 washed RBC units (IQR 244-1066) per patient over 12 years (IQR 5-18 years), most commonly for recurrent, non-severe allergic reactions. There were no transfusion reactions with unwashed RBCs aside from one patient with one episode of pruritus and another with recurrent pruritus, which was typical even with washed RBC. We decreased the mean number of washed RBC units per month by 72.9% (104 ± 10 vs. 28.2 ± 25.2; p < .0001) and saved US $100.25 per RBC unit., Conclusion: Washing of RBCs may be safely reconsidered in chronically transfused patients without a history of anaphylaxis. Washing should be implemented judiciously due to potential lack of necessity and logistical/operational challenges., (© 2023 AABB.)

Background: Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy., Study Design and Methods: The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions. Outcomes included mortality, sepsis, and subsequent platelet transfusion requirements., Results: Following adjustment for possible confounding factors, no statistically significant association between ABO non-identical platelet transfusion and increased risk of mortality was observed in the overall cohort of 21,176 recipients. However, when analyzed by diagnostic category and recipient ABO group, associations with increased mortality for major mismatched transfusions were noted in two of eight subpopulations. Hematology/Oncology blood group A and B recipients (but not group O) showed a Hazard Ratio (HR) of 1.29 (95%CI: 1.03-1.62) and intracerebral hemorrhage group O recipients (but not groups A and B) showed a HR of 1.75 (95%CI: 1.10-2.80). Major mismatched transfusions were associated with increased odds of receiving additional platelet transfusion each post-transfusion day (through day 5) regardless of the recipient blood group., Discussion: We suggest that prospective studies are needed to determine if specific patient populations would benefit from receiving ABO identical platelet units. Our findings indicate that ABO-identical platelet products minimize patient exposure to additional platelet doses., (© 2023 AABB.)

Background: Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8)., Methods: MERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated., Discussion: Screening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda., Trial Registration: Mirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669 . Registered on 9 November 2018., (© 2022. The Author(s).)

Background: In 2019, the United States Food and Drug Administration published its final recommendations to mitigate bacterial contamination of platelets. We sought to evaluate our secondary bacterial culture (SBC) strategy in light of those recommendations., Study Design and Methods: A retrospective analysis was conducted of SBC data (October 2016-2019) at our institution. SBC was performed upon receipt (Day 3 after collection); 5 mL of platelet product was inoculated aseptically into an aerobic bottle and incubated at 35°C for 3 days. For 8 months, a 10-mL inoculum was trialed. No quarantine was applied. All positive cultures underwent Gram staining and repeat culture of the platelet product (if available). A probable true positive was defined as concordant positive culture between the initial and repeat culture. The incidence of probable true- and false-positive cultures were reported descriptively and differences evaluated by sampling volume., Results: Over 3 years, 55 896 platelet products underwent SBC, yielding 30 initial positive results (approx. 1/1863 platelets); 25 (83.3%) signaled within 24 hours of SBC. The rates of probable true positive, false positive, and indeterminate for 5 mL were 0.027% (1/3771), 0.002% (1/45 251) and 0.018% (1/5656), respectively. The respective rates for 10 mL were 0.018% (1/5323), 0.07% (1/1521), and 0%. Seven of eight (87.5%) false-positive SBCs occurred with a 10-mL inoculum. No septic transfusion reactions were reported., Conclusion: SBC continues to interdict bacterially contaminated units of platelets. Our findings suggest higher rates of false positivity using large-volume inocula., (© 2020 AABB.)

Background: Factors associated with red blood cell (RBC), plasma, and platelet transfusions in hospitalized neonates and children across the United States have not been well characterized., Methods: Data from the Kids' Inpatient Database (KID) 2016 were analyzed. KID is a random sample of 10% of all uncomplicated in-hospital births and 80% of remaining pediatric discharges from approximately 4200 US hospitals. Sampling weights were applied to generate nationally representative estimates. Primary outcome was one or more RBC transfusion procedures; plasma and platelet transfusions were assessed as secondary outcomes. Analysis was stratified by age: neonates (NEO; ≤28 d), and nonneonates (PED; >28 d and <18 y). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs)., Results: Among 5,604,984 total hospitalizations, overall prevalence of transfusions was 1.07% (95% CI, 0.94%-1.22%) for RBCs, 0.17% (95% CIs, 0.15%-0.21%) for plasma and 0.35% (95% CI, 0.30%-0.40%) for platelet transfusions. RBC transfusions occurred among 0.43% NEO admissions and 2.63% PED admissions. For NEO admissions, RBC transfusion was positively associated with nonwhite race, longer length of hospitalization, highest risk of mortality (aOR, 86.58; 95% CI, 64.77-115.73) and urban teaching hospital location. In addition to the above factors, among PED admissions, RBC transfusion was positively associated with older age, female sex (aOR, 1.10; 95% CI, 1.07-1.13), and elective admission status (aOR, 1.62; 95% CI, 1.46-1.80). Factors associated with plasma and platelet transfusions were largely similar to those associated with RBC transfusion, except older age groups had lower odds of plasma transfusion among PED admissions., Conclusions: While there is substantial variability in the proportion of neonates and nonneonatal children transfused nationally, there are several similar, yet unique, nonlaboratory predictors of transfusion identified in these age groups., (© 2020 AABB.)

Background: Thrombotic thrombocytopenic purpura (TTP) patients have increased risk for allergic transfusion reactions (ATR) due to the number of plasma products they require. This study evaluated the efficacy of solvent detergent treated plasma (S/D treated plasma) to reduce ATRs., Study Design and Methods: All TTP patients who presented from April 2014 to February 2015 and experienced a moderate-severe ATR to untreated plasma with TPE were switched to S/D treated plasma (Octaplas) for their remaining procedures and included in the study. Patient records were retrospectively reviewed., Results: The overall ATR rate per procedure decreased from 35.0% (95% CI = 15.4%-59.2%) with untreated plasma to 1.4% ([1/73] 95% CI = 0.0%-7.4%) with S/D treated plasma. The moderate-severe ATR rate decreased from 20.0% ([4/20] 95% CI = 5.7%-43.7%) with untreated plasma to 0.0% ([0/73] 95% CI = 0.0%-4.9%) with S/D treated plasma. The overall ATR rate per plasma unit decreased from 2.6% (95%CI = 1.0%-5.1%) with untreated plasma to 0.1% (95% CI = 0.0%-0.4%) with S/D treated plasma. No patients experienced VTE while receiving untreated plasma. Four patients experienced VTE events while receiving S/D treated plasma. All patients who experienced a VTE had additional risk factors for VTE., Conclusion: S/D plasma has promise as an effective product to reduce the risk of ATRs in TTP patients. Given the high risk of ATR in TTP patients, consideration of S/D plasma instead of untreated plasma for TPE in these patients may be warranted, especially for patients with a history of moderate to severe ATR. More extensive studies are needed to confirm these findings., (© 2019 AABB.)

Background: Bacterial contamination and associated septic transfusion reactions (STRs) remain the leading infectious risk to the blood supply. We sought to characterize the risk and clinical presentation of blood culture-positive transfusion reactions (BCPTRs) and STRs at our institution., Study Design and Methods: A retrospective analysis was conducted of all suspected transfusion reactions reported to the transfusion service at a 1000-bed tertiary academic medical center from January 2009 to September 2016. Routine investigation included review of the clinical presentation, Gram stain, and bacterial culture of residual blood from the transfused product or associated blood bag. BCPTRs were defined by the presence of a positive bacterial culture in the blood product and/or recipient. STRs met definitive Centers for Disease Control and Prevention hemovigilance criteria for transfusion-transmitted infection, with definite imputability and concordant bacterial culture of the blood product and recipient., Results: A total of 688,514 blood products were transfused during the study period, 3170 transfusion reactions were reported, and 18 (0.57%) were BCPTRs of which seven (0.22%) were STRs. Fifteen of 18 (83.3%) BCPTRs and six of seven (85.7%) were associated with transfusion of apheresis platelets. Major symptoms and signs of BCPTRs included chills (67%), fever (61%), and nausea and vomiting (50%). Four of seven (57.1%) STRs were classified as severe or life-threatening., Conclusion: BCPTRs are rare yet potentially serious. The signs and symptoms of BCPTRs, and associated STRs, are not specific, posing risk of misclassification. Challenges surrounding reporting and case ascertainment underscore the need for laboratory measures to address residual risk of contamination., (© 2018 AABB.)

Background and Objectives: Many hospitals require transfusions to be discontinued when vital signs stray from predetermined ranges, regardless of clinical symptoms. Variations in vital signs may be unrelated to transfusion, however, and needlessly stopping a transfusion may delay medical care while increasing donor exposures and healthcare costs. We hypothesized that a detailed study of vital sign changes associated with transfusion of blood product by component, including those associated with potential reactions (complicated) and those deemed to be uncomplicated, would establish a useful framework of reference for treating clinicians and transfusion services alike., Materials and Methods: A retrospective electronic record review of transfusion service and transfusion recipient data was completed on 3852 inpatient transfusion episodes over a 6-month period at four academic tertiary care hospitals across the United States. Vital signs pre- and post-transfusion were recorded by trained clinical research nurses. Serious reactions were adjudicated by a panel of transfusion medicine experts., Results: In both uncomplicated transfusions (n = 3765) and those including an adverse reaction (n = 87), vital sign fluctuations were generally modest. Compared to uncomplicated transfusions, transfusions complicated by febrile reactions were associated with higher pretransfusion temperature and higher pretransfusion pulse rates. Episodes of transfusion circulatory overload were associated with higher pretransfusion respiration rates compared to uncomplicated transfusions., Conclusion: Most transfusions are associated with only modest changes in vital signs. Pretransfusion vital signs may be an important yet previously understudied predictor of vital sign changes during transfusion. The optimal role of vital sign assessment during blood transfusion deserves further study., (© 2017 International Society of Blood Transfusion.)

Background: Prevalence estimates of the serious hazards of transfusion vary widely. We hypothesized that the current reporting infrastructure in the United States fails to capture many transfusion reactions and undertook a multicenter study using active surveillance, data review, and adjudication to test this hypothesis., Study Design and Methods: A retrospective record review was completed for a random sample of 17% of all inpatient transfusion episodes over 6 months at four academic tertiary care hospitals, with an episode defined as all blood products released to a patient in 6 hours. Data were recorded by trained clinical research nurses, and serious reactions were adjudicated by a panel of transfusion medicine experts., Results: Of 4857 transfusion episodes investigated, 1.1% were associated with a serious reaction. Transfusion-associated circulatory overload was the most frequent serious reaction noted, being identified in 1% of transfusion episodes. Despite clinical notes describing a potential transfusion association in 59% of these cases, only 5.1% were reported to the transfusion service. Suspected transfusion-related acute lung injury/possible transfusion-related acute lung injury, anaphylactic, and hypotensive reactions were noted in 0.08, 0.02, and 0.02% of transfusion episodes, respectively. Minor reactions, including febrile nonhemolytic and allergic, were noted in 0.62 and 0.29% of transfusion episodes, respectively, with 30 and 50% reported to the transfusion service., Conclusion: Underreporting of cardiopulmonary transfusion reactions is striking among academic, tertiary care hospitals. Complete and accurate reporting is essential to identify, define, establish pathogenesis, and mitigate/treat transfusion reactions. A better understanding of the failure to report may improve the accuracy of passive reporting systems., (© 2016 AABB.)

Background: Prophylactic antigen-matching can reduce alloimmunization rates among chronically transfused patients with sickle cell disease (SCD), but this matching increases costs and may only benefit 30% of patients. We assessed the clinical and financial value of a potential assay for alloimmunization risk that would allow for targeted antigen-matching., Study Design and Methods: A Markov-based model evaluated direct medical costs and alloimmunization events over 10 to 20 years among transfused (simple or exchange) patients with SCD. Four matching strategies were evaluated: prospective matching (for all patients), history-based matching (only for patients with prior alloimmunization), perfectly informed matching (assay with 100% sensitivity, 100% specificity), and imperfectly informed matching (reduced accuracy). Under all matching protocols, matching included C, E, K, and any additional alloantibodies present. A hospital perspective was adopted, with costs (2012US$) and events discounted (3%)., Results: Perfectly informed antigen-matching using a $1000 assay is expected to save $82,334 per patient over 10 years, compared to prospective matching. Perfectly informed antigen-matching is more costly than history-based matching, but reduces alloimmunization events by 45.6% over 10 years. Averting each alloimmunization event using this strategy would cost an additional $10,934 per patient. Imperfectly informed antigen-matching using an assay with 75% specificity and 75% sensitivity is less costly than prospective matching, but increases alloimmunization events. Compared to history-based matching, imperfectly informed matching would decrease alloimmunization events by 32.61%, at an additional cost of $147,915 per patient over 10 years. Cost-effectiveness of informed antigen-matching is largely driven by assay specificity., Conclusions: A sufficiently specific assay to inform antigen-matching may be cost-effective in reducing alloimmunization among transfused patients with SCD., (© 2014 AABB.)

Background: Both cardiopulmonary bypass (CPB) and red blood cell (RBC) storage are associated with detrimental changes in RBC structure and function that may adversely affect tissue oxygen delivery. We tested the hypothesis that in cardiac surgery patients, RBC deformability and aggregation are minimally affected by CPB with autologous salvaged blood alone but are negatively affected by the addition of stored allogeneic blood., Methods: In this prospective cohort study, 32 patients undergoing cardiac surgery with CPB were divided into 3 groups by transfusion status: autologous salvaged RBCs alone (Auto; n = 12), autologous salvaged RBCs + minimal (<5 units) stored allogeneic RBCs (Auto+Allo min; n = 10), and autologous salvaged RBCs + moderate (≥5 units) stored allogeneic RBCs (Auto+Allo mod; n = 10). Ektacytometry was used to measure RBC elongation index (deformability) and critical shear stress (aggregation) before, during, and for 3 days after surgery., Results: In the Auto group, RBC elongation index did not change significantly from the preoperative baseline. In the Auto+Allo min group, mean elongation index decreased from 32.31 ± 0.02 (baseline) to 30.47 ± 0.02 (nadir on postoperative day 1) (P = 0.003, representing a 6% change). In the Auto+Allo mod group, mean elongation index decreased from 32.7 ± 0.02 (baseline) to 28.14 ± 0.01 (nadir on postoperative day 1) (P = 0.0001, representing a 14% change). Deformability then dose-dependently recovered toward baseline over the first 3 postoperative days. Changes in aggregation were unrelated to transfusion (no difference among groups). For the 3 groups combined, mean critical shear stress decreased from 359 ± 174 mPa to 170 ± 141 mPa (P = 0.01, representing a 54% change), with the nadir at the end of surgery and returned to baseline by postoperative day 1., Conclusions: In cardiac surgery patients, transfusion with stored allogeneic RBCs, but not autologous salvaged RBCs, is associated with a decrease in RBC cell membrane deformability that is dose-dependent and may persist beyond 3 postoperative days. These findings suggest that autologous salvaged RBCs may be of higher quality than stored RBCs, since the latter are subject to the so-called storage lesions.

Background: Hyperkalemic cardiac arrest is a potential complication of massive transfusion in children. Our objective was to identify risk factors and potential preventive measures by reviewing the literature on transfusion-associated hyperkalemic cardiac arrest (TAHCA) in the pediatric population., Study Design and Methods: Literature searches were performed in MEDLINE and the Cochrane Database of Systematic Reviews., Results: We identified nine case reports of pediatric patients who had experienced cardiac arrest during massive transfusion. Serum potassium concentration was reported in eight of those reports; the mean was 9.2 ± 1.8 mmol/L. Risk factors for TAHCA noted in the case reports included infancy (n = 6); age of red blood cells (RBCs; n = 5); site of transfusion (n = 5); and the presence of comorbidities such as hyperkalemia, hypocalcemia, acidemia, and hypotension (n = 9). We also identified 13 clinical studies that examined potassium levels associated with transfusion. Of those 13, five studied routine transfusion, two were registries, and six examined massive transfusion., Conclusions: Key points identified from this literature search are as follows: 1) Case reports are skewed toward infants and neonates in particular and 2) the rate of blood transfusion, more so than total volume, cardiac output, and the site of infusion, are key factors in the development of TAHCA. Measures to reduce the risk of TAHCA in young children include anticipating and replacing blood loss before significant hemodynamic compromise occurs, using larger-bore (>23-gauge) peripheral intravenous catheters rather than central venous access, checking and correcting electrolyte abnormalities frequently, and using fresher RBCs for massive transfusion., (© 2013 American Association of Blood Banks.)

Background: Transfusion-related acute lung injury (TRALI) is an uncommon but serious transfusion reaction. Studies have shown that the transfusion of HLA and HNA antibodies in donor plasma can lead to TRALI. Female donors are more likely to have such antibodies due to alloantigen exposure during pregnancy. Many blood suppliers have now implemented various TRALI risk reduction strategies to unknown effect. A retrospective analysis of TRALI reactions in plasma recipients before and after the conversion to low-TRALI-risk plasma (all-male donor plasma, male-predominant plasma, nulliparous female plasma, and HLA antibody-tested plasma) is reported., Study Design and Methods: Transfusion reaction reports at three large hospitals 16 months before and 16 months after the conversion to low-TRALI-risk plasma were analyzed. Respiratory reactions were categorized as TRALI, possible TRALI, or other (e.g., transfusion-associated circulatory overload or allergic reactions). Reactions were reported as a percentage of total units transfused and rates for the two time periods were compared. Trends in reaction rates for other components were also compared., Results: A total of 2156 transfusion reactions in association with 461,598 transfused blood components were reviewed. The incidence of combined TRALI or possible TRALI reactions, due to the transfusion of plasma, decreased from 0.0084% to zero (p = 0.052). The rate of TRALI or possible TRALI reactions in red blood cell and platelet recipients did not change significantly., Conclusion: The conversion to low-TRALI-risk plasma has reduced the incidence of TRALI reactions in plasma recipients., (© 2011 American Association of Blood Banks.)

Background: Mechanisms of allergic transfusion reactions (ATRs) are not well understood. The aim of this study was to distinguish recipient-, donor-, and product-specific factors associated with ATRs., Study Design and Methods: We conducted a retrospective cohort study of apheresis platelet (AP) products transfused from April 2000 through March 2010. The concordance rate of ATRs when split AP products were transfused to at least two individuals was compared to the overall ATR rate among all AP products. Per-person ATR rates also were compared to the overall ATR rate., Results: We observed 1616 ATRs among 93,737 transfusions, for an overall incidence of 1.72% (95% confidence interval [CI], 1.64%-1.81%). Of the 1616 ATRs, 630 occurred when split AP products were transfused to at least two recipients. Of these 630 AP products, ATRs were observed in at least two different recipients of the same AP collection only 6 of 630 times, for a concordant incidence of 0.95% (95% CI, 0.35%-2.06%), which is similar to the overall ATR rate (p = 0.17). On an individual level, 30.0% of recipients had ATR rates of more than 5%, and these 30.0% accounted for 62.1% of ATRs. Donors of AP products associated with concordant ATRs donated AP products that had an ATR rate of 5.8% (95% CI, 3.1%-9.7%), which is higher than the overall ATR rate (p < 0.001)., Conclusions: An observed ATR does not predict an ATR in a different recipient of a split AP product. A minority of platelet recipients accounts for the majority of ATRs. Some donors are strongly associated with ATRs. Consequently, recipient and donor factors are implicated in the mechanism of ATRs., (© 2010 American Association of Blood Banks.)

Background: The incidence of allergic transfusion reactions (ATRs) ranges from 1% to 3% of all transfusions, and they are difficult to prevent. This study evaluated whether removing plasma from apheresis platelets (APs) or red blood cells (RBCs) by concentrating or washing transfusion products can decrease the incidence of ATRs., Study Design and Methods: A retrospective cohort study of 179 individuals who received unmanipulated and subsequently concentrated and/or washed APs was conducted. Poisson regression with generalized estimating equations was used to estimate the incident rate ratios and 95% confidence intervals (CIs) of ATRs., Results: The incidence of ATRs to unmanipulated APs was 5.5% (306 ATRs/5575 AP units). The incidence decreased to 1.7% (135 ATRs/4327 AP units) when individuals received concentrated APs (73% reduction; 95% CI, 65%-79%) and 0.5% (21 ATRs/4082 AP units) when individuals received washed APs (95% reduction; 95% CI, 91%-97%). Of the 39 individuals who received unmanipulated RBCs and subsequently washed RBCs, the incidence of ATRs decreased from 2.7% (33 ATRs/1236 RBC units) to 0.3% (2 ATRs/733 RBC units; 89.4% reduction; 95% CI, 55.5%-97.5%). The median number of AP transfusions to first ATR was six (interquartile range [IQR], 2-19) for unmanipulated APs and increased to 13 (IQR, 4-32) for concentrated APs and 40 (IQR, 29-73.5) for washed APs., Conclusions: Concentrating APs and washing APs and RBCs substantially reduces ATRs, suggesting that the plasma component of APs and RBCs has an essential role in the etiology of ATRs., (© 2010 American Association of Blood Banks.)

In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of alloimmunization caused by the transfusion of allogeneic blood components and to evaluate potential approaches to both reduce its occurrence and manage its effects. Significant sequelae of alloimmunization were discussed and identified, including difficulties in maintaining chronic transfusion of red blood cells and platelets, hemolytic disease of the newborn, neonatal alloimmune thrombocytopenia, and rejection of transplanted cells and tissues. The discussions resulted in a consensus that identified key areas of future research and developmental areas, including genetic and epigenetic recipient factors that regulate alloimmunization, biochemical specifics of transfused products that affect alloimmunization, and novel technologies for high-throughput genotyping to facilitate extensive and efficient antigen matching between donor and recipient. Additional areas of importance included analysis of unappreciated medical sequelae of alloimmunization, such as cellular immunity and its effect upon transplant and autoimmunity. In addition, support for research infrastructure was discussed, with an emphasis on encouraging collaboration and synergy of animal models biology and human clinical research. Finally, training future investigators was identified as an area of importance. In aggregate, this communication provides a synopsis of the opinions of the working group on the above issues and presents both a list of suggested priorities and the rationale for the topics of focus. The areas of research identified in this report represent potential fertile ground for the medical advancement of preventing and managing alloimmunization in its different forms and mitigating the clinical problems it presents to multiple patient populations., (© 2011 American Association of Blood Banks.)

Background: Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion-related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined., Study Design and Methods: A total of 8171 volunteer blood donors were prospectively recruited by six US blood centers from December 2006 to May 2007. Donors provided a detailed history of pregnancy and transfusion and a sample for HLA Class I and II antibody testing by multiantigen bead flow analysis., Results: A total of 8171 donors were enrolled; 7920 (96.9%) had valid HLA antibody test results and 7841 (99%) of those had complete pregnancy and transfusion information. The prevalence of any HLA antibody was similar in nontransfused (n = 1138) and transfused (n = 895) men, 1.0% versus 1.7% (p = 0.16). HLA antibodies were detected in 17.3% of all female donors (n = 5834) and in 24.4% of those with a history of previous pregnancy (n = 3992). The prevalence of HLA antibodies increased in women with greater numbers of pregnancy: 1.7% (zero), 11.2% (one), 22.5% (two), 27.5% (three), and 32.2% (four or more pregnancies; p < 0.0001)., Conclusion: HLA Class I and Class II antibodies are detectable at low prevalence in male donors regardless of transfusion and in female donors without known immunizing events. The prevalence of HLA antibodies increases significantly with more pregnancies. These data will allow blood centers to estimate the impact of HLA antibody testing as a potential TRALI risk reduction measure.

Background: Transfusion-associated circulatory overload (TACO) can be difficult to diagnose and distinguish from transfusion-related acute lung injury (TRALI), but is a relatively common complication that occurs when increases in blood volume overwhelm the cardiovascular system. Brain natriuretic peptide (BNP) has been shown to be a functional marker for TACO. N-terminal pro-brain natriuretic peptide (NT-proBNP) is another marker that could be more helpful than BNP since it has a longer half-life in circulation and is also much more stable in laboratory samples. In this study, whether NT-proBNP is a useful diagnostic marker for TACO was evaluated., Study Design and Methods: Forty patients were enrolled into a case-control study (16 patients with TACO and 24 control patients) and had pre- and posttransfusion NT-proBNP concentrations evaluated from submitted type-and-screen blood samples., Results: The sensitivity of elevated posttransfusion NT-proBNP to diagnose TACO was 93.8 percent, the specificity was 83.8 percent, and the accuracy was 87.5 percent. Elevated posttransfusion NT-proBNP is the only independent variable for the diagnosis of TACO based on multivariate logistic regression., Conclusion: NT-proBNP is both a sensitive and a specific marker for TACO and can be helpful in confirming transfusion associated fluid overload. This study also demonstrates that many patients who experience TACO may already be in a state of excess volume. Clinicians should be aware that many asymptomatic patients have excess fluid and transfusion may cause these patients to become symptomatic.

Delayed hemolytic transfusion reactions (DHTRs) are a well-known complication of transfusion that may be defined as immune-mediated hemolysis of allogeneic donor red cells that occurs approximately 3 to 5 days after transfusion. In general, DHTRs occur in patients who have been alloimmunized previously, but the antibody titers have fallen below serologically detectable levels. Transfusion of seemingly compatible blood and exposure to the putative alloantigen results in an anamnestic immune response that may lead to in vivo accelerated destruction of donor red cells. Symptoms may include a drop in hemoglobin and hematocrit, fever, jaundice, and renal insufficiency. More recent studies have shown that there is a subset of cases called delayed serologic transfusion reactions (DSTRs) when there are serologic findings consistent with DHTRs but no clinical evidence of hemolysis. In both DHTRs and DSTRs, direct antiglobulin tests are often persistently positive long after the transfused donor red cells should have been removed from the circulation. Because the studies required to investigate the immunologic and clinical aspects of these reactions are precluded in humans, we developed an animal model for the study of DHTRs and DSTRs. Our article provides a comprehensive review of DHTRs and DSTRs, the role of complement and cytokines in these reactions, and the phenomenon of bystander hemolysis. We describe our studies using the rabbit as a model for the study of DHTRs and bystander hemolysis., (Copyright 2001 by W.B. Saunders Company)

The discovery of AIDS in the 1980s and its rapid evolution as a major concern for physicians and their patients have led to many questions about the safety of the blood supply. The attention placed on AIDS has led to new discoveries and technologies to reduce the risk of other transfusion complications such as hepatitis, bacterial contamination, and transfusion-associated graft-vs-host disease. Concerns about blood safety have focused much attention on alternative blood transfusion strategies such as autologous blood, viral inactivation, and artificial blood substitutes. This review describes the transfusion medicine delivery system in the United States, with special emphasis on evolving developments and their implications for the discipline of chemical pathology.

Background: A hemolytic transfusion reaction (HTR) due to anti-IH is reported in a patient with sickle cell disease (SCD)., Case Report: An 18-year-old woman with SCD and a complete phenotype on file had been identified as group B-positive with negative antibody-screening tests and had received 1 unit of packed RBCs. Ten days later, she was readmitted in painful crisis with a Hb of 4.2 g per dL. Antibody-screening tests and panel cells were positive at all test phases with a negative autocontrol, which suggested alloantibodies. Phenotypically matched group O RBCs were issued emergently. After the transfusion of 100 mL, the patient had an HTR with chills, fever, and tachycardia and laboratory findings of hemoglobinemia, hemoglobinuria, and negative DATs. A high-titer, IgM anti-IH with a high thermal amplitude (reactive with group O, but not group B RBCs at 37 degrees C) was identified. Autologous RBCs appeared to have normal I antigen expression, but less H antigen than pooled group B RBCs. She was given group B RBCs, uneventfully, by use of a blood warmer., Conclusions: This is a rare case of anti-IH as the cause of a HTR, as a serologic problem that may be seen in SCD, and as an autoantibody that may mimic an alloantibody. Ironically, this HTR resulted from the effort to provide phenotypically matched RBCs, which necessitated the selection of group O RBCs.

Background: Bystander hemolysis may be defined as the destruction of antigen-negative red cells during immune hemolysis, such as delayed hemolytic transfusion reaction (DHTR). Although many have suspected that bystander hemolysis does occur, that phenomenon is very difficult to document., Study Design and Methods: Five patients with sickle cell disease (SCD) who underwent exchange transfusion and subsequently experienced a DHTR were retrospectively evaluated. Serial samples were examined for complete blood counts, the percentage of hemoglobin A and S, and the percentage of reticulocytes. The total red cell count and the percentage of hemoglobin S were used to calculate the hemoglobin S red cell count. The patients' profiles were compared to proposed models., Results: DHTRs due to anti-E, -S, -Fy(a), or -Jk(a) or serologically undetectable antibodies were identified 7 to 19 days after exchange transfusion. All patients had a significant decrease in hemoglobin A red cells; 56.4 to 94.7 percent of hemoglobin A red cells were hemolyzed. Patients 4 and 5 had a decrease in hemoglobin S red cells which indicated the destruction of autologous red cells during DHTR. The evidence for bystander hemolysis was particularly convincing in Patient 5, because there was a substantial decrease in hemoglobin S red cells despite a reticulocyte production index of 2.2 percent at the nadir of the DHTR., Conclusion: Hemoglobin S provides a biologic marker for monitoring autologous red cell loss in sickle cell patients. We have shown one patient with clinical evidence of bystander hemolysis complicating a DHTR.

Objective: To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and II (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors., Design: A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991., Setting: Cardiac surgery services of three large tertiary care hospitals., Patients: The study included 11,532 patients in three hospitals who had cardiovascular surgery., Measurements: Incident HIV-1 and HTLV-I or HTLV-II infection., Results: We detected two new HIV-1 infections among patients transfused with 120,312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% CI of 0.0053%. Before donor screening for HTLV-I, transfusion of 51,026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69,272 units, a rate of 0.0014%. A corresponding HTLV-I/II-infected donor was found for this patient., Conclusion: Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmitted HIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60,000 units.

Background: The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown., Methods: From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive., Results: Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 patients receiving transfusions since the addition in May 1990 of screening for antibodies to HCV, the risk was 0.57 percent per patient (0.03 percent per unit). The trend toward decreasing risk with increasingly stringent screening of donors was statistically significant (P less than 0.001). After we controlled for the method of donor screening, the risk of seroconversion was strongly associated (P less than 0.001) with the volume of blood transfused, but not with the use of particular blood components., Conclusions: The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV. The current risk of post-transfusion hepatitis is about 3 per 10,000 units transfused.

Objective: To determine the medical and laboratory characteristics of bacteremia secondary to transfusion of microbiologically contaminated platelet concentrates., Design: Febrile transfusion reactions were prospectively monitored over 42 months. Units involved in reactions were evaluated with Gram's stain and culture tests., Setting: Comprehensive cancer center., Patients: Patients receiving platelet transfusions for thrombocytopenia secondary to bone marrow failure., Result: Seven cases of transfusion-associated sepsis were observed. Multidonor platelet products stored for 5 days resulted in an incidence of sepsis five times higher than those stored for 4 days or less (P less than .01). Investigation indicates that contamination most likely occurred at the time of blood collection. Clinically, septic reactions were associated with greater temperature elevations (average increase, 2.0 degrees C) than febrile reactions to sterile products., Conclusions: Contamination of platelet concentrates remains a significant clinical problem. Septic episodes may be reduced by transfusion of platelets with shorter storage intervals.

Delayed serologic transfusion reactions (DSTRs) and delayed hemolytic transfusion reactions (DHTRs) were studied in a large tertiary-care hospital. A DSTR was defined by the posttransfusion finding of a positive direct antiglobulin test (DAT) and a newly developed alloantibody specificity. A DHTR was defined as a DSTR case that showed clinical and/or laboratory evidence of hemolysis. Thirty-four cases of DSTR, 70 percent of which were due to anti-E and/or -Jka, were documented prospectively over a 20-month period. Retrospective review of the medical records found clinical evidence of hemolysis in only 6 (18%) of the 34. Thus, the incidence of DSTR was 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, whereas the incidence of DHTR was only 1 (0.12%) of 854 patients tested. Fifteen of the 34 patients were followed for up to 174 days after reaction. Twelve of the 15 still demonstrated a positive DAT with anti-IgG only. Eluate studies indicated that the persistence of a positive DAT after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies. This study indicates 1) that DSTRs are a frequent finding in multiply transfused patients, although most cases are benign and fail to meet rigid criteria for DHTR, and 2) that the persistence of a positive DAT after DSTR or DHTR is common.

Hemolytic transfusion reactions typically are explained by red cell serologic incompatibilities. We describe a patient in whom a clinically significant red cell alloantibody could not be demonstrated, despite the occurrence of several clinically severe hemolytic reactions. Serologic studies using multiple techniques demonstrated only an anti-Bga; these studies included standard procedures as well as more sensitive experimental techniques. A 51Cr survival study using red cells from a random unit, compatible in vitro with conventional techniques, showed 72 percent survival at 1 hour and 7 percent survival at 24 hours. R2R2 (hr" (e) negative) red cells in a second 51Cr survival study showed 90 percent survival at 1 hour and 92 percent survival at 6 hours. The patient was transfused with R2R2 units which were tolerated well and survived normally. Extensive serologic testing still demonstrated only an anti-Bga. A third 51Cr survival study, 10 months after the first study, with an R1R1 (hr" (e) positive) sample showed 90 percent survival at 1 hour and 42 percent survival at 6 hours. A fourth study using a larger aliquot of R2R2 (hr"(e)negative) 51Cr-labeled red cells, examined over 2 weeks showed a near normal 21-day survival of 50 percent. These 51Cr survival studies, along with normal survival of hr" (e) negative units, suggest that this patient destroys hr" (e) positive red cells despite negative serologic testing.

Posttransfusion purpura typically occurs in PLA1 negative blood recipients who have been previously immunized to the PLA1 antigen. Following transfusion, severe thrombocytopenia develops with the formation of anti-PLA1. Since the patients' platelets lack the PLA1 antigen, one would not expect this antibody to destroy autologous platelets. In this study we show that PLA1 antigen exists in stored blood and can absorb to PLA1 negative platelets making them PLA1 reactive. Incubating PLA1 (-) platelets with ultracentrifuged plasma from PLA1 (+) blood donors allowed anti-PLA1 to bind to PLA1 (-) platelets. Control plasma from PLA1 (-) blood donors did not lead to anti-PLA1 binding. Using an inhibition assay, we showed that stored blood contains PLA1 material that was not removed by ultracentrifugation. The material absorbing to PLA1 (-) platelets represented the PLA1 antigen, which was confirmed by Western blotting. After incubating plasma containing PLA1 antigen with PLA1 (-) platelets, reactivity at 95,000 D was observed. Native PLA1 (+) platelets showed a similar band. When PLA1 (-) platelets were incubated with plasma from a PLA1 (-) donor, this band was not present. These studies show that a soluble form of PLA1 antigen exists in stored blood that can absorb to PLA1 (-) platelets. Consequently, anti-PLA1 can bind to these platelets leading to thrombocytopenia. These observations may explain the autologous destruction of platelets in posttransfusion purpura.

The devastating transfusion reaction that can occur after the infusion of blood contaminated with bacteria has prompted blood banks to adopt practices designed to minimize the possibility of bacterial contamination. There are four recognized sources of contamination of blood collected for transfusion: 1) prior contamination of the bag or the anticoagulant solution; 2) airborne contamination of the needle; 3) inadequate skin preparation including coring of the skin; and 4) bacteremia in the donor. The use of plastic collection bags and specially designed needles, and the recognition of the importance of aseptic technique have drastically reduced the incidence of serious transfusion reactions due to contamination. The history obtained from the donor prior to phlebotomy also eliminates many donors who could have bacteria in their blood at the time of donation. Improved collection techniques and the deferral of potential high risk donors have made serious reactions from contaminated blood a rare occurrance.

In a 3-month period four episodes of bacterial sepsis related to contaminated random donor platelet concentrates were observed. Evaluation incriminated extended (5 or more days) platelet storage. To determine if platelets stored for longer periods were likely to have greater bacterial contamination, platelet concentrates were inoculated with bacteria and daily quantitative bacteriology was performed. In vitro studies using polyolefin bags indicated contamination could occur with a single organism of Staphylococcus epidermidis. By 72 hours, platelet concentrates contained from 10(3) to 10(8) organisms per 0.1 ml depending on the inoculum size. By 6 days all inoculated units contained 10(7) to 10(9) organisms per 0.1 ml.