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Since the beginning of the COVID-19 pandemic, the use of convalescent plasma as a possible treatment has been explored. Here we describe our experience as the first U.S. organization creating a COVID-19 convalescent plasma program to support its use through the single-patient emergency investigational new drug, the National Expanded Access Program, and multiple randomized controlled trials. Within weeks, we were able to distribute more than 8000 products, scale up collections to more than 4000 units per week, meet hospital demand, and support randomized controlled trials to evaluate the efficacy of convalescent plasma treatment. This was through strategic planning; redeployment of staff; and active engagement of hospital, community, and public health partners. Our partners helped with donor recruitment, testing, patient advocacy, and patient availability. The program will continue to evolve as we learn more about optimizing the product. Remaining issues to be resolved are antibody titers, dose, and at what stage of disease to transfuse. [ABSTRACT FROM AUTHOR]

Background: Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-associated mortality for which multiple mitigation strategies have been implemented over the past decade. However, product-specific TRALI rates have not been reported longitudinally and may help refine additional mitigation strategies.Study Design and Methods: This retrospective multicenter study included analysis of TRALI rates from 2007 through 2017. Numerators included definite or probable TRALI reports from five blood centers serving nine states in the United States. Denominators were components distributed from participating centers. Rates were calculated as per 100,000 components distributed (p < 0.05 significant).Results: One hundred four TRALI cases were reported from 10,012,707 components distributed (TRALI rate of 1.04 per 100,000 components). The TRALI rate was 2.25 for female versus 1.08 for male donated components (p < .001). The TRALI rate declined from 2.88 in 2007 to 0.60 in 2017. From 2007 to 2013, there was a significantly higher TRALI rate associated with female versus male plasma (33.85 vs. 1.59; p < 0.001) and RBCs (1.97 vs. 1.15; p = 0.03). From 2014 through 2017, after implementation of mitigation strategies, a significantly higher TRALI rate only from female-donated plateletpheresis continued to be observed (2.98 vs. 0.75; p = 0.04).Conclusion: Although the TRALI rates have substantially decreased secondary to multiple strategies over the past decade, a residual risk remains, particularly with female-donated plateletpheresis products. Additional tools that may further mitigate TRALI incidence include the use of buffy coat pooled platelets suspended in male donor plasma or platelet additive solution due to the lower amounts of residual plasma. [ABSTRACT FROM AUTHOR]

Background: Blood centers may offer point-based reward systems or cardiovascular disease (CVD) screening to incentivize donors. However, combining these incentives to improve CVD risk and blood donation rates has not been studied.Study Design and Methods: Study was a three-arm prospective controlled trial: Group 1, control (routine points, no CVD screening); Group 2, CVD screening with routine points; and Group 3, CVD screening plus incentive double points. The primary objective was to determine if double versus routine incentive points led to improvement or maintenance of CVD risk profile assessed using self-reported changes in 1) reading food labels for calorie and fat content, 2) exercising daily, 3) reduced fat intake, and 4) increase in eating fruits and vegetables. Outcomes were compared at first and final (2-year) follow-up visits. As secondary outcome, median blood donation rates before enrollment and during study were compared.Results: A total of 570 donors (290 in Group 1, 134 in Group 2, 146 Group 3) were selected. At first follow-up visit, 71.4% in Group 3 versus 62.0% in Group 2 subjects reported at least one of four positive behavioral changes (p < 0.001). Increase in reading food labels for calorie and fat content was the most common change and higher in Group 3 (Group 3 from 60.9% to 79.1%; Group 2 from 67.6% to 77.5%; p < 0.001). Final evaluation showed significant increase in self-reported exercise in Group 3 only (from baseline 52.9% to 68.3%; p < 0.05). Group 3 reported higher increase in median number of donations/year during study enrollment (6.8 [IQR, 4.3-12] vs. baseline 4.6 [IQR, 3.2-7.1] donations/year) than Group 2 (5.6 [IQR, 4.2-10.5] vs. baseline 4.9 [IQR, 3.5-10.2]) and Group 1 (4.4 [IQR, 2.7-8.0] vs. baseline 4.4 [IQR, 2.5-6.0] donations/year; p < 0.001).Conclusion: Positive donor reinforcement (double vs. routine points) resulted in better self-reported health maintenance behavior and increased donation rates. [ABSTRACT FROM AUTHOR]

Background: Expanding the African American (AA) donor pool is critical to sustain transfusion support for sickle cell disease patients.Study Design and Methods: The aims were to: 1) apply cognitive computing on donation related metrics to develop a predictive model that effectively identifies repeat AA donors, 2) determine whether a single e-mail communication could improve AA donor retention and compare retention results on higher versus lower predictive score donors, and 3) evaluate the effect of e-mail marketing on AA donor retention with culturally versus nonculturally tailored message.Results: Between 2011 and 2012, 30,786 AA donors donated blood at least once on whom predictive repeat donor scores (PRDSs) was generated from donor-related metrics (frequency of donations, duration between donations, age, blood type, and sex). In 2013, 28% (8657/30,786) of 2011 to 2012 donors returned to donate on whom PRDS was validated. Returning blood donors had a higher mean PRDS compared to nonreturning donors (0.649 vs. 0.268; p < 0.001). In the e-mail pilot, high PRDS (≥0.6) compared to low PRDS (<0.6) was associated with 89% higher donor presentation rate (p < 0.001), 20% higher e-mail opening rate (p < 0.001), and, specifically among those who opened the e-mail, 159% higher presentation rate (p < 0.001). Finally, blood donation rate did not differ (p = 0.79) as a function of generic (n = 9312, 1.4%) versus culturally tailored (n = 9326, 1.3%) message.Conclusion: Computational algorithms utilizing readily available donor metrics can identify highly committed AA donors and in conjunction with targeted e-mail communication has the potential to increase the efficiency of donor marketing. [ABSTRACT FROM AUTHOR]

Background: Each unit of blood donated is processed and stored individually resulting in variability in the amount of red blood cells (RBCs) collected, RBC properties, and the 24-hour posttransfusion RBC survivability. As a result, each unit differs in its ability to deliver oxygen and potentially its effects on the recipient. The goal of this study was to investigate the storage of pooled RBCs from multiple donors in comparison to control standard RBC units.Study Design and Methods: Two units of irradiated, leukoreduced RBCs of same ABO, D, E, C, and K antigen phenotype were collected from each of five donors using apheresis. One unit from each donor was pooled in a 2-L bag and remaining units were used as controls. After being pooled, RBCs were separated in five bags and stored at 4°C along with the controls. Quality indexes were measured on Days 2, 14, and 28 for all the units.Results: Adenosine triphosphate assays for both pooled and controls showed a slight decrease from Day 2 to Day 28 (pooled/control from 5.22/5.24 to 4.35/4.33 µmol/g hemoglobin [Hb]). 2,3-Diphosphoglycerate was successfully rejuvenated for all RBC units on Day 28 (pooled 11.46 µmol/g Hb; control 11.86 µmol/g Hb). The results showed a nonsignificant difference between pooled and control units, with a general trend of lower standard deviation for pooled units when compared to controls.Conclusion: Pooled units have reduced unit-to-unit variability. Future exploration of their immunogenicity is required before using pooled units for transfusion. [ABSTRACT FROM AUTHOR]

Background: Two studies were performed to test the effectiveness of riboflavin and ultraviolet (UV) light treatment (Mirasol PRT, Terumo BCT) against murine cytomegalovirus (MCMV). The first study utilized immune-compromised mice to measure the reduction of cell-free MCMV. A second study used a murine model to evaluate the ability of Mirasol PRT to prevent transfusion-transmitted (TT)-MCMV infection.Study Design and Methods: Human plasma was inoculated with MCMV and then treated with Mirasol PRT. The viral titer was measured using an infectious dose 50% assay in nude mice. Mice were euthanized on Day 10 posttransfusion, and their spleens were tested for the presence of MCMV DNA using polymerase chain reaction (PCR). Mirasol PRT was also evaluated to determine its effectiveness in preventing TT-MCMV in platelets (PLTs) stored in PLT additive solution. PLTs were inoculated with either cell-associated MCMV or cell-free MCMV and then treated with Mirasol PRT. Mice were transfused with treated or untreated product and were euthanized 14 days posttransfusion. Blood and spleens were assayed for MCMV DNA by real-time-PCR.Results: Using nude mice to titer MCMV, a modest 2.1-log reduction was observed in plasma products after Mirasol PRT treatment. TT-MCMV was not observed in the mouse transfusion model when either cell-free or cell-associated MCMV was treated with Mirasol PRT; MCMV transmission was uniformly observed in mice transfused with untreated PLTs.Conclusions: These results suggest that using riboflavin and UV light treatment may be able to reduce the occurrence of transmission of human CMV from infectious PLTs and plasma units. [ABSTRACT FROM AUTHOR]

Background Individuals with sickle cell disease ( SCD), thalassemia, and leukemia often require frequent transfusion and run the risk of red blood cell ( RBC) alloimmunization. To prevent alloimmunization or when alloimmunization is present, phenotype-matched and antigen-negative RBCs are transfused. To increase the probability of a phenotypic match, donors and recipients should share the same racial and/or ethnic background. Because the majority of patients with SCD are of African and Hispanic or Latino descent, a donor base of racial and ethnic minority donors providing an adequate supply of antigen-negative RBC units that can be phenotypically matched is required to meet the needs of frequently transfused patients. Study Design and Methods The New York Blood Center began the Precise Match program in 2005 to increase donations among African American and Hispanic/ Latino donors by 150 incremental units per month. To evaluate the program, we conducted a systematic analysis of program documentation, focus group results, and collections data by race and ethnicity over time. Results The program achieved 75% of the operationalized goal of a 150-unit-per-month increase; 75% of donors were first-time donors, with deferral rates at new drives as high as 50%. Significant time and effort was involved in cultivating the community connections that facilitated new drives. Conclusions Although Precise Match fell short of targets, it served as a foundation for relationships with diverse communities. Further research is needed to understand better how to increase minority donation using existing infrastructure and in the face of market pressures to collect blood as efficiently as possible. [ABSTRACT FROM AUTHOR]

Background Lack of ready access to a donation site may be a potential barrier to or influence the frequency of blood donations. In this study, we applied geographic analysis to blood donor behavior and use of different donation sites. Study Design and Methods The study population consisted of blood donors who gave whole blood in Georgia between 2004 and 2008. Zip code, city, and county of donor's residence were matched with the addresses of their donation sites. Donors were dichotomized as either nonmetro Atlanta or metro Atlanta residents. Six donation site categories were defined: donation within the same or a different zip code, within the same or a different city, and within the same or a different county. Logistic regression was used to compare donations by zip code, city, and county. Results The study population consisted of 402,692 blood donors who donated 1,147,442 whole blood units between 2004 and 2008, more than half of whom (56.4%) resided in the metro Atlanta area. The majority of donors were white (75.0%) and female (55.7%). In nonmetro Atlanta, repeat donors were more likely to have donated at fixed sites (p < 0.001). In metro Atlanta, repeat donors were more likely to have donated at a mobile site than at a fixed site (p < 0.001). Conclusion Geographic and demographic differences in blood donation patterns exist. The locations of donor residences and blood donation sites influence donor behaviors. Understanding the geographic influence on donation patterns provides an important tool for optimizing donor recruitment strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood centers have Implemented public health initiatives, including cardiovascular disease (CVD) screening, to improve donor and com-munity health and serve as an incentive to donate. STUDY DESIGN AND METHODS: CVD risk screening and counseling were performed at mobile blood drives in diverse neighborhoods. Risk factors were determined by point-of-care testing (total cholesterol, high-density lipoprotein, and hemoglobin A1c levels), interviews, and physical examinations (body mass index, waist circum-ference, and blood pressure). Results were confiden-tially relayed to participant by health counselors. A 60-day follow-up survey was sent to some participants. RESULTS: Over 11 months, 2406 participants (44% male; mean age 28 ± 16; 67% minority racial/ethnic group) were screened at 290 mobile drives. A total of 92% of participants had medical insurance. A total of 14% had none, 26% one, 33% two, and 27% three or more risk factors. A total of 72% of teenage participants had at least one risk factor. A total of 18% of partici-pants who were taking medications for risks were poorly controlled. A total of 15% had newly identified risks. A total of 711 participants completed follow-up survey: 21% sought medical care, 51% were motivated to change their lifestyle, 81% were pleased with screen-ing, 48% were more likely to donate, and 62% recom-mended donation to friends and family because of the screening. CONCLUSION: CVD risk screening and counseling can occur during a mobile blood drive. A majority of partici-pants screened had risk factors. Follow-up surveys showed that the program was well received. Further studies are planned to evaluate long-term effects of the program on donor health and donor return rates. [ABSTRACT FROM AUTHOR]

BACKGROUND: The prevalence of blood donor eligibility factors has a major impact on the availability of blood donors and thus the blood supply in the United States. The prevalence of these factors may differ between demographic groups and thus help explain the differences in blood donation rates. STUDY DESIGN AND METHODS: The study population (18-69 years old who were African American [AA], white, or Hispanic) was 185,073,489. Forty eligibility factors determined by US Food and Drug Administration's Code of Federal Regulations and AABB Standards for Blood Banks and Transfusion Services were used to calculate whole blood donation eligibility rates. Eligibility data were obtained from the 2007 to 2008 National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, US Census Bureau, and Centers for Disease Control and Prevention. Eligibility rates were determined by race/ethnicity, sex, and age groups (18-39 and 40-69 years). RESULTS: In 2007 to 2008, 122 million Americans (65.9% of the study population and 41.0% of the total US population) were estimated to be eligible to donate blood in the United States. Significant differences in eligibility rates by demographic characterizers were determined (p < 0.001): AAs (36.5%), whites (46.4%), and Hispanics (40.7%); males (45.4%) and females (42.7%); individuals 18 to 39 years old (35.8%); and individuals 40 to 69 years old (32.9%). CONCLUSIONS: AAs were significantly less eligible to donate blood than whites and Hispanics. Disparities in donor eligibility exist by race/ethnicity, sex, and age groups. [ABSTRACT FROM AUTHOR]

In this article, the author discusses the role and effect of 2-(diethylhexyl) phthalate (DEHP) in blood storage bags. They note that DEHP as a plasticizer helps to increase bag flexibility, red blood cell (RBC) survival, and platelet (PLT) storage's oxygen permeability. However, they assert that DEHP poses potential damage to the environment and adverse health effects due to its toxicity including disorders of reproductive system, behavioral disorders, and an increase risk for obesity.

The article comments on the risks associated with transfusion of D+ blood components, particularly red blood cells (RBCs) and blood platelets (PLTs), to D- individuals. It is said that due to the possibility of D sensitization, such transfusion to D- individuals, especially females of childbearing potential, has been a subject of concern. Reference is made to the article "Platelet transfusions from D+ donors to Dpatients: a ten year follow-up study of 1014 patients," by J. Cid et al.

Historically, African Americans have a general mistrust for the health care system that has contributed to significant health disparities. The goal of this study was to evaluate whether this distrust among African Americans affects attitudes toward blood donation. Fifteen African American churches in metropolitan Atlanta participated in an 81-item self-administered survey. The questionnaire assessed barriers and motivators for, and knowledge and beliefs about, blood donation in African Americans. Bivariate analysis and logistic regression models were performed. A total of 930 individuals responded to the survey. This group was 99% African Americans, 71% female, and 84% college educated, 54% with a household income of at least $50,000 and mean age of 47 ± 14 years. Donation history was 3% current donors, 46% lapsed donors, and 40% nondonors. Respondents who trusted versus distrusted hospitals had more knowledge of the blood supply and less fear of donation and were more likely to respond to blood needs of the community. In a multivariate logistic regression model, donors were more likely to trust hospitals (p = 0.003) and were more likely to have participated in research (p < 0.001) than nondonors. African American distrust of the health care system is associated with decreased likelihood of previous blood donation. This may be secondary to donor centers being viewed as a component of the health care system. Building trust between donor centers and African American community by ensuring the safety of donation may increase African American blood donation rates. [ABSTRACT FROM AUTHOR]

The article focuses on the history of blood banking and transfusion medicine profession. It states that physicians were initially focused on technical and consultative medical aspects including blood collection, proper use of blood products, and blood collection. The first blood bank was established by Bernard Fantus at Cook County Hospital. It also mentions that the House of Delegates of the American Medical Association adopted the requirement of a physician during blood transfusion in 1963.

One proposed mechanism of extracorporeal photopheresis (ECP) in reducing chronic graft-versus-host disease (cGVHD) is alteration in numbers of circulating dendritic cells (DCs). This hypothesis was tested by correlating numbers of DC precursors and T cells in the blood before and during ECP therapy with response of cGVHD. Twenty-five patients with cGVHD were treated with ECP. Data were collected with emphasis on blood cellular markers, clinical response to ECP, and overall survival. Fourteen patients (56%) responded and had better 2-year survival than nonresponders (88% vs. 18%, p = 0.003). Responders had higher baseline circulating myeloid DC (mDC) and plasmacytoid DC precursors and CD4+ and CD8+ T cells compared with nonresponders. Receiver operating characteristic curve analyses showed that the best baseline cutoff values to predict response to ECP were mDC counts of 3.7 cells/µL (79% sensitivity, 82% specificity) and CD4+ T-cell counts of 104 cells/µL (71% sensitivity, 82% specificity). CD4+ T cells declined in responders over time, but not in nonresponders, and no significant changes were seen in CD8 T-cell or DC numbers over a 12-month period in responder or nonresponder groups. Higher baseline numbers of circulating DCs and T cells may predict clinical response to ECP in patients with cGVHD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Platelet (PLT) storage adversely affects PLT structure and function in vitro and is associated with decreased PLT recovery and function in vivo. In pediatric transfusion medicine, it is not uncommon for small residual volumes to remain in parent units after aliquot preparation of leukoreduced apheresis-derived PLTs (LR-ADP). However, limited data exist regarding the impact of storage on residual small-volume LR-ADP. STUDY DESIGN AND METHODS: Standard metabolic testing was performed on residual volumes of LR-ADP after aliquot removal and PLT aggregometry using a dual agonist of ADP and collagen was performed on stored, small-volume aliquots (10-80 mL) created from an in vitro model of PLT storage. RESULTS: Seventy-seven LR-ADP underwent metabolic (n = 67) or metabolic and aggregation (n = 10) studies. All products maintained a pH value of more than 6.89 throughout storage. Lactate and pCO2 increased proportionally with longer storage time. Regardless of acceptable metabolism during storage, aggregation in 10- to 20-mL aliquots was impaired by Day 4 and aliquots less than 40 mL demonstrated the most dramatic decrease in aggregation from baseline. CONCLUSIONS: Despite maintenance of acceptable metabolic conditions, residual volumes of LR-ADP develop impaired aggregation in vitro that may adversely affect PLT survival and function in vivo. At volumes below 40 mL, LR-ADP revealed reduced aggregation. As a result, it is recommended to monitor and record volumes of LR-ADP used for pediatric transfusion. Moreover, once LR-ADP attain a volume of 50 mL or less on Day 4 or Day 5 of storage, consider discarding these products until their in vivo efficacy can be studied. [ABSTRACT FROM AUTHOR]

BACKGROUND: HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion-related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized. STUDY DESIGN AND METHODS: Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics. RESULTS: A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80-3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%-11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68-12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07-1.80). In a linear probability model, the estimated additive risk of transfusion-induced alloimmunization was only 0.8% (95% CI, −0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously. CONCLUSION: Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whole blood donation in the United States is restricted in volume to 10.5 mL/kg or less in an effort to prevent hypovolemic reactions, but still may exceed more than 15% of a donor's estimated blood volume (EBV). We analyzed the association of EBV with prefaint and systemic vasovagal reactions (SVRs) among whole blood donors and the potential impact of an EBV-based deferral policy. STUDY DESIGN AND METHODS: Independent predictors for prefaint reactions and SVRs were assessed by multivariate logistic regression analysis on 591,177 unique donors participating in the Retrovirus Epidemiology Donor Study-II study. RESULTS: Young age (16 years old odds ratio [OR], 3.70; 95% confidence interval [CI], 2.78-4.94), low EBV (<3.5 L OR, 3.30; 95% CI, 2.57-4.23), and first-time donation status (OR, 2.33; 95% CI, 2.03-2.67) were the strongest predictors for SVRs, with similar trends seen for prefaint reactions. Sex, height, race, blood center, and donation site were weakly associated predictors. A total of 5.6% of all donors had an EBV of less than 3.5 L and experienced 12.5% of all prefaint reactions and 14.5% of SVRs. The highest reaction rates were seen in donors less than 23 years old with an EBV of less than 3.5 L who comprised 2.7% of all donors, who were mostly female (99.9%), and who experienced 8.8% of prefaint reactions and 11.0% of SVRs. CONCLUSION: Young age, low EBV, and first-time donation status are the major correlates of prefaint reactions and SVRs, suggesting that high school and college donors are at particular risk. Deferral of donors with low EBV who are less than 23 years old may offer a rational approach to protecting donors at greater risk of reactions without jeopardizing the adequacy of the blood supply. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pediatric transfusion medicine (PTM) is a subspecialty of transfusion medicine with no formal training program and few specialists. The Pediatric Transfusion Medicine Academic Awardees (PedsTMAA) group surveyed PTM content experts to identify relevant objectives for the first formal PTM curriculum. STUDY DESIGN AND METHODS: Eight North American PTM experts were invited to participate in a two-step consensus process. PTM-related objectives compiled from a review of existing training documents were organized into a survey. Experts were asked to rate each objective for relevancy for a clinical pathology trainee. Content validity indexes (CVIs) and asymmetric confidence intervals (ACIs) of expert ratings and analysis of respondents' comments were used to identify relevant objectives. RESULTS: Six experts participated and reviewed 117 objectives. Based on content validity criteria (CVI ≥ 0.83 and lower-limit 95% ACI ≥ 3), a total of 65 objectives were considered relevant. Twenty-three objectives were rated “very relevant” by all the experts while some proposed objectives were determined to be not relevant, out of date, or inappropriate for a resident trainee level. CONCLUSIONS: The PedsTMAA group identified 65 objectives for a PTM curriculum. Twenty-three represent a clear core set of objectives and should be considered for clinical pathology training. The next step is to consider the teaching strategies and evaluation methods that will be employed to best deliver this content addressing competency in medical knowledge. [ABSTRACT FROM AUTHOR]

BACKGROUND: Data-driven practices in preoperative red blood cell (RBC) preparation for pediatric surgical procedures are not well established. Adaptation of established adult preparation guidance methods to pediatric populations may improve perioperative RBC utilization. STUDY DESIGN AND METHODS: A retrospective audit of preoperative RBC preparation volumes (Vp) and intraoperative RBC transfusion volumes (Vt) for pediatric surgical procedures was undertaken at a large children's hospital from January to June 2006. RBC preparation-to-transfusion volume (mL/kg) ratios (P:T) were calculated for all surgeries, subspecialties, and select procedures. P:T equals Vp divided by Vt. Resulting P:Ts were compared to a target P:T of 2:1. A model for maximum procedure-specific Vp (Vp-max) defined Vp-max as the RBC transfusion volume able to meet the needs of 80% of patients undergoing an individual surgical procedure. Vp-max values were applied to the study data set to predict the impact on P:Ts and Vp. RESULTS: RBCs were prepared for 332 surgical procedures and transfused during 113 procedures. P:T was 3.5:1 for total surgical procedures (subspecialty range, 2.7:1-46:0), exceeding the 2:1 target. Vp-max modeling for spinal fusion, craniotomy for neoplasia, craniotomy for seizure, and craniosynostectomy yielded P:T ratios of 1.5:1, 1.5:1, 1.7:1, and 1.0:1, respectively, predicting a 30% decrease in Vp for these four surgical procedures. CONCLUSIONS: P:Ts for pediatric surgical procedures at this institution indicate potentially excessive preoperative RBC preparations. Determination of data-driven procedure-specific Vp may increase the efficiency of preoperative RBC preparation practices. [ABSTRACT FROM AUTHOR]

BACKGROUND: Red blood cell (RBC) alloimmunization can be a serious complication of blood transfusion, but factors influencing the development of alloantibodies are only partially understood. Within FDA-approved time limits, RBCs are generally transfused without regard to length of storage. However, recent studies have raised concerns that RBCs stored for more than 14 days have altered biologic properties that may affect medical outcomes. To test the hypothesis that storage time alters RBC immunogenicity, we utilized a murine model of RBC storage and alloimmunization. STUDY DESIGN AND METHODS: Blood from transgenic HOD donor mice, which express a model antigen (hen egg lysozyme [HEL]) specifically on RBCs, was filter leukoreduced and stored for 14 days under conditions similar to those used for human RBCs. Fresh or 14-day-stored RBCs were transfused into wild-type recipients. The stability of the HOD antigen and posttransfusion RBC survival were analyzed by flow cytometry. RBC alloimmunization was monitored by measuring circulating anti-HEL immunoglobulin levels. RESULTS: Transfusion of 14-day-stored, leukoreduced HOD RBCs resulted in 10- to 100-fold higher levels of anti-HEL alloantibodies as detected by enzyme-linked immunosorbent assay than transfusion of freshly collected, leukoreduced RBCs. RBC expression of the HOD antigen was stable during storage. CONCLUSIONS: These findings demonstrate that HOD murine RBCs become more immunogenic with storage and generate the rationale for clinical trials to test if the same phenomenon is observed in humans. Length of storage of RBCs may represent a previously unappreciated variable in whether or not a transfusion recipient becomes alloimmunized. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent data from military and civilian centers suggest that mortality is decreased in massive transfusion patients by increasing the transfusion ratio of plasma and platelet (PLT) products, and fibrinogen in relationship to red blood cell (RBC) products during damage control resuscitation and surgery. This study investigates the relationship of plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios to mortality in massively transfused patients at a civilian Level 1 trauma center. STUDY DESIGN AND METHODS: Demographic, laboratory, transfusion, and outcome data were collected prospectively from February 1, 2007, to January 31, 2009, and retrospectively from February 1, 2005, to January 31, 2007, on all injured patients who underwent massive transfusion (defined as ≥10 RBC products within 24 hr). Mortality was analyzed in relation to the plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios using both univariate and multivariate analyses. RESULTS: A total of 214 patients received massive transfusion secondary to traumatic injury. High versus low transfusion ratios were associated with improved 30-day survival: plasma:RBC 59% versus 44%, p = 0.03; PLT:RBC 63% versus 33%, p < 0.01; and cryoprecipitate:RBC 66% versus 41%, p < 0.01. By multivariable stepwise logistic regression analysis, increased plasma:RBC (p = 0.02) and PLT:RBC (p = 0.02), and decreased age (p = 0.02), ISS (p < 0.01) and total RBCs (p = 0.03) were statistically associated with improved 30-day survival. CONCLUSIONS: In the civilian setting, plasma, PLT, and cryoprecipitate products significantly increased 30-day survival in trauma patients. Future prospective randomized clinical trials are required to determine the optimal transfusion ratios. [ABSTRACT FROM AUTHOR]

BACKGROUND: Historically, minority populations have represented only a small proportion of US blood donors, but recent trends in immigration and potential blood shortages emphasize the need for recruitment strategies to increase minority donations. STUDY DESIGN AND METHODS: Donation data from a network of six US blood centers for 2006 were analyzed. Race/ethnicity, country of birth, and educational attainment data were collected specifically for the study and assessed for their influence on donation behavior. Logistic regression was used to determine independent associations with repeat donors status and annual donation frequency. RESULTS: A total of 1,288,998 donations from 729,068 donors were studied; most donors had data on race/ethnicity (97.1%) and country of birth (93.1%). The proportion of minority donors differed by blood center, with African American donors (16%) most common at the Southeastern blood center and Asian (12%), Hispanic (13%), and foreign-born donors (13%) most common at the Northern California blood center. Minority donors and those born in Mexico or Latin America were younger than white donors. Minority and non–US-born donors were less likely than white and US-born donors to be repeat donors (odds ratio [OR], 0.60-0.78), and most were less likely to give two or more annual donations (OR, 0.82-1.11). CONCLUSION: Minority and Mexico/Latin America–born donors represent a younger and often first-time donor population compared to white and US-born donors, but their annual donation frequency was only slightly lower than white and US-born donors. Increasing the retention and donation frequency of minorities will be important for supplementing the blood supply. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sickle cell disease (SCD) patients have unique transfusion considerations during bone marrow transplantation (BMT), including prophylaxis against stroke and alloimmunization. Characterization of transfusion requirements is important for blood bank and clinician patient management. STUDY DESIGN AND METHODS: A retrospective analysis of red blood cell (RBC) and platelet (PLT) transfusion of SCD patients during myeloablative matched sibling donor (MSD) BMT at one institution from 1993 to 2007 was performed. Patient characteristics (RBC blood group antibodies, ABO-incompatible donor, BMT-related morbidity) and transfusion practices (RBC phenotype matching, transfusion threshold, and blood age) were assessed for effect on total RBC transfusion volumes. RESULTS: Twenty-seven patients received MSD BMT with 96% survival and 0% rejection. Six alloimmunized patients received RBCs with extended phenotype matching (C, c, E, e, K, Fya, Jkb), 14 nonalloimmunized received limited matching (C, c, E, e, K), and 7 did not have phenotype matching. Among 26 survivors, a median seven RBC transfusions (range, 3-15) and 13.5 PLT transfusions (range, 4-48) per patient were administered, equivalent to 64 mL/kg RBCs (range, 22-122 mL/kg) and 106 mL/kg PLTs (range, 26-343 mL/kg). BMT-related morbidity predicted increased RBC transfusions (p = 0.006). Venoocclusive disease was associated with greater RBC (p = 0.016) and PLT transfusion volumes (p = 0.016). Greater phenotype matching was associated with decreased RBC transfusions (p = 0.0247). CONCLUSIONS: SCD patients have high transfusion support during MSD BMT. Communication of BMT complications to the blood bank is essential for transfusion inventory management. Phenotype matching decreased RBC transfusions in this cohort and warrants further investigation in SCD transfusion therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Storage of red blood cells (RBCs) is necessary for an adequate blood supply. However, reports have identified potential negative sequelae of transfusing stored RBCs. An animal model would be useful to investigate the pathophysiology of transfusing stored RBCs. However, it has been reported that storage of rat RBCs in CPDA-1 resulted in an unexpected sudden decline in posttransfusion survival. A mouse model of RBC storage and transfusion was developed to assess survival kinetics of mouse RBCs. STUDY DESIGN AND METHODS: RBCs expressing green fluorescent protein were collected in CPDA-1, filter leukoreduced, adjusted to a 75% hematocrit, and stored at 4°C. At weekly intervals, stored RBCs were transfused into C57BL/6 recipients. RBC survival was measured by flow cytometry and chromium-51 labeling. Phosphatidylserine externalization and CD47 expression was also evaluated. RESULTS: Mean 24-hour survivals of transfused RBCs were 99, 91, 64, 54, 30, and 18% after 0, 7, 14, 21, 28, and 35 days of storage, respectively. Stored RBCs showed an initial rapid clearance with subsequent extended survival. Increased surface phosphatidylserine and decreased CD47 expression were also observed. CONCLUSIONS: Mouse RBCs showed a progressive decline in survival, as a function of storage time, unlike the precipitous loss of viability reported for rat RBCs. Moreover, changes in the measured surface markers were analogous to trends reported for human RBCs. Together, these findings provide an initial characterization of a novel mouse model of RBC storage with the potential to serve as an experimental platform for studying the pathophysiologic consequences of transfusing stored RBCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several differences exist between antigens on transfused red blood cells (RBCs) and other immunogens, including anatomical compartmentalization. Whereas antigens from microbial pathogens and solid organ transplants drain into local lymph nodes, circulating RBCs remain segregated in the peripheral circulation, where they are consumed by antigen-presenting cells (APCs) in the spleen and liver. Accordingly, it was hypothesized that the splenic APCs play a central role in primary alloimmunization to transfused RBCs. STUDY DESIGN AND METHODS: Recipient mice were splenectomized and transfused with transgenic RBCs expressing the membrane-bound hen egg lysozyme (mHEL) model RBC antigen. In some experiments, mHEL-specific CD4+ T cells were adoptively transferred into recipient mice to allow investigation of helper T-cell responses. Unmanipulated or sham-splenectomized mice served as controls. Recombinant murine cytomegalovirus expressing mHEL (mHEL-MCMV) was used as a control non-RBC immunogen. Humoral responses were measured by mHEL-specific enzyme-linked immunosorbent assay and flow cytometric–based RBC cross-match. RESULTS: Control animals synthesized detectable anti-HEL immunoglobulin (Ig)G after a single mHEL RBC transfusion. mHEL-specific CD4+ T cells underwent robust expansion, and adoptive transfer of CD4+ T cells resulted in a 1000-fold increase in anti-HEL IgG. In contrast, minimal anti-HEL IgG was detectable in splenectomized mice, mHEL-specific CD4+ T cells did not proliferate, and adoptive transfer did not increase anti-HEL IgG. However, anti-HEL IgG response after exposure to mHEL-MCMV was equivalent in control and splenectomized mice. DISCUSSION: Together, these findings illustrate the distinct properties of transfused RBCs as immunologic stimuli, with the spleen playing a critical role in primary RBC alloimmunization at the level of CD4+ T-cell activation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood donation is a medical procedure with attendant risks, and thus blood donors should undergo acceptable informed consent. There are no guidelines for the informed consent forms (ICFs) for whole blood donors or for parental consent forms (PCFs) for minor age blood donors. The goal of the study was to determine if the majority of the generally accepted elements of informed consent are provided to volunteer allogeneic whole blood donors in the United States. STUDY DESIGN AND METHODS: ICFs and PCFs along with their accompanying general information forms (GIFs) from nonmilitary blood collection establishments for allogeneic whole blood donation were collected throughout the United States and scored using a system based on the essential elements of informed consent derived from guidelines of consent for research subjects. The overall score for each ICF and PCF was obtained. RESULTS: Twenty-one ICFs and 37 PCFs from 48 states representing major collection centers within the United States were scored. The mean score for the common essential elements ICFs was 35 percent (range, 10%-80%) and for PCFs was 46 percent (range, 10%-90%). CONCLUSION: None of the whole blood allogeneic donation informed consents surveyed contained all the common essential or specific blood donation information desired. There is a need for national guidelines for the informed consent process for both the donor and the parent of a minor to ensure adequate information is specified. [ABSTRACT FROM AUTHOR]

Many significant events have occurred in the recent past that beg a broad audience to address the question “What is pediatric transfusion medicine?” Herein, we list some of these events and their relevance below and attempt to provide an answer for this question. Indeed, several issues regarding the subspecialty of pediatric transfusion medicine (PTM) are particularly timely, and it appears that a critical mass, or a nidus capable of becoming a critical mass, is developing in PTM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Factors influencing alloimmunization to transfused red blood cells (RBCs) are not well understood. Utilizing a murine model, we have recently reported that RBC alloimmunization is enhanced by recipient treatment with viral-like polyinosinic polycytidylic acid (poly(I:C)). To determine whether a different subtype of inflammation also enhances RBC alloimmunization, we investigated the effects of the bacterial endotoxin lipopolysaccharide (LPS) on alloimmunization. STUDY DESIGN AND METHODS: Mice were treated with poly(I:C) or LPS; in select experiments, the precursor frequency of naïve antigen-specific CD4+ T cells was increased using T cells from T-cell receptor transgenic mice. Recipients were transfused with leukoreduced RBCs expressing the membrane-bound hen egg lysozyme (mHEL) antigen, and alloimmunization was measured by anti-HEL immunoglobulin G responses using enzyme-linked immunosorbent assay and flow cytometric cross-match. Costimulatory molecule expression was examined on antigen-presenting cells (APCs) by flow cytometry. RESULTS: Increased expression of costimulatory molecules on APCs was seen after treatment with either poly(I:C) and LPS. In contrast to the enhancement of RBC alloimmunization observed after treatment with poly(I:C), LPS not only failed to enhance but also actively suppressed alloimmunization, even in the presence of increased mHEL-specific CD4+ T cells (p < 0.001 LPS vs. control). CONCLUSIONS: These data demonstrate that the regulation of RBC alloimmunization by inflammatory stimuli is complex, including enhancement by a viral-like stimulus and suppression by a bacterial-type stimulus. The mechanism(s) are unlikely to involve variation in the costimulatory molecules studied, because only subtle differences on APCs were observed after treatment with poly(I:C) and LPS. [ABSTRACT FROM AUTHOR]

BACKGROUND: The American Red Cross (ARC) initiated a comprehensive donor hemovigilance program in 2003. We provide an overview of reported complications after whole blood (WB), apheresis platelet (PLT), or automated red cell (R2) donation and analyze factors contributing to the variability in reported complication rates in our national program. STUDY DESIGN AND METHODS: Complications recorded at the collection site or reported after allogeneic WB, apheresis PLT, and R2 donation procedures in 36 regional blood centers in 2006 were analyzed by univariate and multivariate logistic regression. RESULTS: Complications after 6,014,472 WB, 449,594 PLT, and 228,183 R2 procedures totaled 209,815, 25,966, and 12,282 (348.9, 577.5, and 538.3 per 10,000 donations), respectively, the vast majority of which were minor presyncopal reactions and small hematomas. Regional center, donor age, sex, and donation status were independently associated with complication rates after WB, PLT, and R2 donation. Seasonal variability in complications rates after WB and R2 donation correlated with the proportion of donors under 20 years old. Excluding large hematomas, the overall rate of major complications was 7.4, 5.2, and 3.3 per 10,000 collections for WB, PLT, and R2 procedures, respectively. Outside medical care was recorded at similar rates for both WB and automated collections (3.2 vs. 2.9 per 10,000 donations, respectively). CONCLUSION: The ARC data describe the current risks of blood donation in a model multicenter hemovigilance system using standardized definitions and reporting protocols. Reported reaction rates varied by regional center independently of donor demographics, limiting direct comparison of different regional blood centers. [ABSTRACT FROM AUTHOR]

The National Heart, Lung, and Blood Institute (NHLBI) supports major research programs related to the field of transfusion medicine, which encompass blood banking, the practice of transfusion medicine itself, and cellular therapies. Specific programmatic elements have included 1) the Transfusion Medicine/Hemostasis Clinical Trials Network (TMH CTN) charged with conducting clinical trials in transfusion medicine and hemostasis; 2) the Retrovirus Epidemiology Donor Study–II (REDS-II), which includes domestic and international efforts dedicated to blood donor safety and blood availability issues; 3) the Specialized Centers of Clinically Oriented Research (SCCOR) in Transfusion Biology and Medicine that include two major projects, the Biologic and Immunologic Aspects of Transfusion Medicine Program and the Transfusion and Lung Injury Program, and 4) the Transfusion Therapy Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS), a Phase III clinical trial that has as its major goal to determine whether a more aggressive transfusion strategy in surgery patients with cardiovascular disease (or risk factors) is associated with improved functional recovery and decreased risk of adverse postoperative outcomes. Notably, none of these programs supports epidemiologic and clinical outcomes research focused on transfusion recipients. Thus, on October 31, 2007, a Working Group on Transfusion Recipient Epidemiology and Outcomes Research was convened by the NHLBI. This group was asked to discuss the current status of the field, identify critical research needs, and make recommendations to the NHLBI program staff. [ABSTRACT FROM AUTHOR]

Blood bank serology has identified hundreds of red blood cell (RBC) antigens contained within numerous blood group systems. Although most blood group antigens are defined by amino acid polymorphisms in the extracellular domain of membrane proteins, it is also possible that additional nonexofacial polymorphisms (NEPs) may exist within cytoplasmic or transmembrane domains. To assess this possibility, we analyzed several blood group molecules by searching the SNPper database for nonsynonymous single-nucleotide polymorphisms. We report the identification of a number of NEPs in the Kell, Kidd, and Duffy molecules. Because the identified NEPs are not exposed on the surface of intact RBCs and are, thus, not accessible to recipient antibodies, they would neither be detected by blood bank serology in vitro, nor would they be recognized targets in hemolytic transfusion reactions in vivo. The presentation of peptides containing NEPs by recipient MHC Class II molecules, however, would nevertheless produce helper T-cell epitopes. In addition to identifying NEPs in human blood group molecules, we explore a novel hypothesis that the presence of NEPs contributes to the immunogenicity of blood group antigens. We further hypothesize that NEPs provide a mechanism by which transfusion can lead to anti-RBC autoantibodies, which are known to occur in humans after transfusion. The scientific basis, existing evidence, approaches to testing, and predicted biology of this hypothesis are presented. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the pediatric population, hemolysis after out-of-group platelet (PLT) transfusion is a potentially fatal event that is thought to be underrecognized. Group A patients transfused with group O single-donor PLTs (SDPs) with “high-titer” anti-A are at greatest risk for hemolysis. STUDY DESIGN AND METHODS: A clinical and serologic evaluation of a pediatric patient with hemolysis of initially unknown etiology was conducted. Retrospective testing for anti-A titer of an admission sample and a transfused group O SDP was performed. RESULTS: The group A patient (previously group O) was found to have a history of engrafted major ABO-mismatched hematopoietic peripheral blood progenitor cell transplant (HPBPCT). Immune-mediated intravascular hemolysis with a delayed presentation was determined. Testing identified passive anti-A in the patient's plasma and high-titer anti-A (IgG 4096, IgM 256) in the group O SDP unit. CONCLUSION: Hemolysis after out-of-group SDP transfusion may be delayed in presentation and, thus, clinically unrecognized. When evaluating these cases, the limitations of routine type and screen for detection of passive anti-A must be considered. Group A individuals with a history of engrafted major ABO-mismatched HPBPCT potentially have increased susceptibility to hemolysis from group O SDP transfusion due to their lack of tissue and soluble A antigen. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Most alloantigens on transfused red blood cells (RBCs) are weakly immunogenic, with only a 2 to 6 percent overall immunization rate even in patients receiving multiple transfusions. Although recipient genetics may contribute to responder and/or nonresponder status, in most cases HLA type does not predict humoral response to RBC antigens. In contrast, rates of alloimmunization do correspond to the underlying disease status of transfusion recipients, suggesting that acquired host factors may play an important role. In this context, it was hypothesized that the inflammatory status of a transfusion recipient would influence immunization to transfused RBCs. STUDY DESIGN AND METHODS: A novel murine model for alloimmunization to RBC antigens was developed with the mHEL mouse, which expresses hen egg lysozyme (HEL) as a model blood group antigen. Leukoreduced mHEL RBCs were transfused into wild-type recipient mice, and anti-HEL responses were monitored. To test the stated hypothesis, some recipient animals were injected with polyinosinic polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA molecule that induces viral-like inflammation. RESULTS: Similar to the immunogenicity of most RBC antigens in humans, transfusion of mHEL RBCs into uninflamed mice was only a weak immunogen. In contrast, poly(I:C)-treated mice had a significant increase in both the frequency and the magnitude of alloimmunization to the mHEL antigen. CONCLUSIONS: These findings demonstrate that recipient inflammation with poly(I:C) significantly enhances humoral immunization to transfused alloantigens in a murine model. Moreover, these data suggest that the inflammatory status of human transfusion recipients may regulate the immunogenicity of transfused RBCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Donor and recipient mechanisms that modulate the incidence and severity of transfusion-transmitted cytomegalovirus (TT-CMV) are unclear. The kinetics of murine CMV (MCMV) infection in the peripheral blood of donor mice were investigated to determine the utility of this model for studying TT-CMV. STUDY DESIGN AND METHODS: BALB/cByJ mice, experimentally infected with Smith strain MCMV, were killed at serial time points up to 28 days after infection. Peritoneal exudate cells (PECs), peripheral blood white blood cells (WBCs), plasma, and marrow were tested for MCMV DNA with quantitative polymerase chain reaction (PCR), replication-competent virus with quantitative culture, and transcription of viral genes with reverse transcription (RT)-PCR targeted at the immediate-early 1 (ie1) gene. RESULTS: PECs, macrophages infected by MCMV shortly after intraperitoneal inoculation, demonstrated high mean levels of MCMV DNA (105-107 genome equivalents [geqs]/105 PECs), virus production (101-104 infectious virions/105 PECs), and ie1 gene transcription, demonstrating productive infection. In contrast, while MCMV loads averaged 104 to 106 geqs per 105 peripheral WBCs, all WBC samples were uniformly negative for MCMV ie1 expression by RT-PCR and for culturable virus, consistent with latent MCMV infection. Plasma and marrow showed lower viral loads than WBCs and PECs and were all negative by culture and RT-PCR analysis. CONCLUSIONS: Following experimental MCMV infection, murine peripheral blood WBCs appear to be latently infected with virus (MCMV DNA–positive; MCMV RNA–negative; MCMV culture–negative), similar to the latently infected human monocytes in peripheral blood of CMV-seropositive donors. These donor kinetics suggest that the experimental MCMV system can be used to effectively model the mechanisms of TT-CMV infections in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recipients of umbilical cord blood (UCB) transplants are susceptible to opportunistic infections, including cytomegalovirus (CMV). To prevent CMV transmission from UCB donors, most laboratories perform serology on corresponding maternal samples and quarantine units when the mother has immunoglobulin M (IgM) anti-CMV. STUDY DESIGN AND METHODS: UCB units and associated samples (UCB plasma and red cell pellet; maternal whole blood and serum) from two cord blood banks were tested with two validated CMV polymerase chain reaction assays (UL54 and UL93 targets). Results were compared with maternal CMV serology (IgG and IgM). RESULTS: Only 4 of 48 (8.3%) quarantined CMV IgM–positive units were also CMV nucleic acid testing (NAT)-positive (651-68,600 copies/mL). In contrast, 1 of 200 “CMV-safe” UCB units (CMV IgM–equivocal or –negative) had CMV DNA (0.5%). The corresponding maternal samples were CMV NAT–negative. Positive maternal IgM serology demonstrates only modest sensitivity (80%) and specificity (82%) and poor positive predictive value (8%), when correlated with the presence of CMV DNA in UCB units. CONCLUSION: CMV NAT may be a useful adjunct to serologic screening, potentially reducing wastage of IgM-positive and NAT-negative units while also detecting potentially infectious units that would pass serologic screening. A prospective clinical trial to further evaluate the role of CMV NAT in UCB transplantation appears warranted. [ABSTRACT FROM AUTHOR]

A photochemical treatment (PCT) process utilizing amotosalen hydrochloride and long wavelength UVA light has been developed to inactivate pathogens in PLTs. This study investigated the effects of amotosalen/UVA treatment on free and latent murine CMV (MCMV) in PLT preparations using a murine model of transfusion-transmitted CMV (TT-CMV). In a model of latent MCMV infection, “donor” mice received 1 × 106 plaque-forming units (PFUs) MCMV and were rested 14 days. Subsequently harvested, pooled, and washed WBCs were PCR positive for MCMV. Murine WBC doses of 1 × 104, 1 × 105, and 1 × 106 were added to human apheresis PLTs in 35 percent autologous plasma and 65 percent PLT AS (PAS). The WBC-PLT products were treated with 150 µmol/L amotosalen and 0.6 J per cm2 UVA and transfused via tail vein injection into recipient mice. Recipients were killed on Day 14. Blood and spleens were collected and assayed for MCMV by PCR. In a parallel model of active infection with free virus, human PLT in 35 percent autologous plasma and 65 percent PAS were dosed with 1 × 105 and 1 × 106 PFUs of MCMV. All other procedures were as described above. In the absence of amotosalen/UVA-pretreatment, transfusion of PLT latently or actively infected with MCMV produced TT-CMV in a dose-dependent fashion. In contrast, all transfusion recipients of identical PLT preparations pretreated with amotosalen/UVA were uniformly PCR negative for MCMV (abrogation of TT-CMV; p < 0.05). PCT of PLT preparations with the specified doses of amotosalen hydrochloride and UVA light prevents transfusion transmission of free and latent MCMV in a murine model. These results suggest that PCT of human PLTs with amotosalen/UVA should also effectively abrogate TT-CMV in the clinical setting. [ABSTRACT FROM AUTHOR]

In January 2003, “white particulate matter” (WPM) was transiently observed in red blood cell (RBC) units collected predominately in the southeastern US. In this report, these events, their chronology, perti-nent observations and investigations, and summaries and conclusions associated with WPM during the 2-week observation period are described. On January 27, 2003, WPM was first identified in RBCs; by January 31, 2003, 110 RBC units containing WPM had been identified. Elective surgeries were postponed. Approxi-mately 400 RBC units containing WPM were inspected in the blood center and characterized into four types: I, II, III, and IV. A variety of preparations of aspirated WPM were made, including light and electron microscopic sections. The rate of WPM-containing units was 1.67 percent (1 in 60 units), whereas the background incidence was less than 0.25 percent. Investigations revealed that WPM was composed of activated and nonactivated platelets (PLTs); no toxins, infectious agents, or agents of bioterrorism were iden-tified. WPM correlated with certain variables studied, including PLT-rich components that had been centrifuged with a “hard spin” before leukoreduction and manu-factured in one vendor's collection sets. Because the increased rate of appearance of WPM was a transient phenomenon, it is not clear whether this is a newly noticed or a new and different phenomenon from “aggregates” observed in the past. [ABSTRACT FROM AUTHOR]

A method for accurate immunohematology testing by fluorescence cytometry (FC) was previously described. Nevertheless, the use of vacuum filtration to wash RBCs and a standard-flow cytometer for data acquisition hindered efforts to incorporate this method into an automated platform. A modified procedure was developed that used low-speed centrifugation of 96-well filter plates for RBC staining. Small-footprint benchtop capillary cytometers (PCA and PCA-96, Guava Technologies, Inc.) were used for data acquisition. Authentic clinical samples from hospitalized patients were tested for ABO group and the presence of D antigen (n = 749) as well as for the presence of RBC alloantibodies (n = 428). Challenging samples with mixed-field reactions and weak antibodies were included. Results were compared to those obtained by column agglutination technology (CAT), and discrepancies were resolved by standard tube methods. Detailed investigations of FC sensitivity and reproducibility were also performed. The modified FC method with the PCA determined the correct ABO group and D type for 98.7 percent of 520 samples, compared to 98.8 percent for CAT (p > 0.05). No-type-determined (NTD) rates were 1.2 percent for both methods. In testing for unexpected alloantibodies, FC determined the correct result for 98.6 percent of 215 samples, compared to 96.3 percent for CAT (p > 0.05). When samples were automatically acquired in the 96-well plate format with the PCA-96, 98.7 percent of 229 samples had correct ABO group and D type determined by FC, compared to 97.4 percent for CAT (p > 0.05). NTD rates were 0.9 and 2.6 percent, respectively. Antibody screens were accurate for 99.1 percent of 213 samples with the PCA-96, compared to 99.5 percent for CAT (p > 0.05). Further investigations demonstrated that FC with the PCA-96 was better than CAT at detecting weak anti-A (p < 0.0001) and alloantibodies. An improved method for FC immunohematology testing has been described. This assay was comparable in accuracy to standard CAT techniques, but had better sensitivity for detecting weak antibodies and was superior in detecting mixed-field reactions (p < 0.005). The FC method demonstrated excellent reproducibility. The compatibility of this assay with the PCA-96 capillary cytometer with plate-handling capabilities should simplify development of a completely automated platform. [ABSTRACT FROM AUTHOR]

Background: Current immunohematology testing methods have limitations including cost, throughput, and adaptability to automation. Furthermore, current automated and semiautomated workstations cannot accommodate many other tests relevant to blood transfusion.Study Design and Methods: Authentic clinical samples from hospitalized patients were tested for ABO group, D type, and presence of RBC alloantibodies by column agglutination technology (CAT), standard tube methods, and a recently developed flow cytometry (FC) technique. Included were challenging samples with rouleaux, autoantibodies, mixed-field reactions, and weak antibodies. Antibody staining of RBCs for FC was initially performed in test tubes and subsequently in microtiter filter plates interfaced with a vacuum manifold.Results: When antibody staining was performed in tubes, FC testing determined the correct ABO group and D type for 99.1 percent of 222 clinical samples, as compared to accuracies of 91.9 percent for CAT and 95.0 percent for standard tube testing. FC testing also detected 99.5 percent of clinically relevant RBC alloantibodies in 239 patient samples, as compared to 98.9 percent for CAT and 94.7 percent for LISS-IAT. Using the FC filter plate technique, 104 of 109 samples (95.4%) were correctly typed for ABO and D (the remaining five samples were read as "no type determined" due to RBC and serum testing discrepancies), and RBC alloantibodies of the IgG and IgM classes were correctly identified in 98.3 percent of samples.Conclusions: Optimized FC testing methods that are comparable in accuracy to standard CAT and tube methods are described. When used with filter plates, this methodology should allow rapid and cost-effective immunohematology testing of both patient and donor samples in an automated workstation format. The same workstation should support automation of other pretransfusion assays that can be analyzed by FC. [ABSTRACT FROM AUTHOR]

Discusses the rarity of detecting cytomegalovirus (CMV) DNA in healthy blood donors using validated polymerase chain reaction assays. Reduction of the incidence of transfusion-transmitted CMV infection cases; Difficulty in evaluating CMV DNA in healthy CMV-seropositive blood donors; Cause of morbidity and mortality in immunocompromised patients.

Reports on the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection. Impairment of bone marrow and peripheral blood responses to both rrIL-3 and rhG-CSF administration, as compared to historic controls; Decrease in the hematopoietic reserve and the response to various cytokines.

Several human CC chemokines have been shown to inhibit HIV/ SIV infection in vitro, providing the rationale for their potential use in vivo. However, because of their inherent physiological effect, such chemokines are reasoned to be of limited therapeutic value due to potential side effects. The knowledge that amino terminus modified Or deleted human RANTES retains its receptor binding properties but loses its signaling properties has provided a means to use such modified chemokines in vivo for possible therapeutic benefits. In efforts to test the efficacy of such modified chemokines, our laboratory has cloned, sequenced, and prepared recombinant forms Of wild-type (wt) and amino-terminus modified rhesus macaque chemokines MIP-1α, MIP1β, and RANTES. These Sets of Chemokines were tested for their potential to inhibit SIV infection and induce signaling. The data showed that whereas wt chemokines retained both virus inhibitory and signaling functions, corresponding amino-terminus modified chemokines only showed vitals inhibitory effects without detectable signaling effects. Such reagents will be valuable for evaluation of their therapeutic potential in vivo, either alone or as adjuncts to other chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]