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<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Despite the vast antigen disparity between donor and recipient red blood cells (RBCs), only 2%–6% of transfusion patients mount an alloantibody response. Recently, RBC antigen density has been proposed as one of the factors that can influence alloimmunization, however, there has been no characterization of the role of antigen density along with RBC dose in primary and secondary immunization.</jats:p></jats:sec><jats:sec><jats:title>Study Design and Methods</jats:title><jats:p>To generate RBCs that express distinct antigen copy numbers, different quantities of hen egg lysozyme (HEL) were coupled to murine RBCs. The HEL‐RBCs were subsequently transfused into recipient mice at different RBC doses and their HEL‐specific IgM, IgG, and IgG subclass response was evaluated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Productive immune responses could be generated through a high copy number antigen transfused at low RBC doses or a low copy number transfused at high RBC doses. Further, primary but submaximal humoral immunization predominantly induced the IgG2b and IgG3 subclasses. In contrast, a maximal primary immunization or a secondary immunization induced all four IgG subclasses.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Our results confirm the existence of an antigen threshold for productive immune responses but indicate that a high antigen copy number alone might not be enough to induce a response, but rather a combination of both antigen copy number and cell dosage may determine the outcome of immunization. Further, this study provides a proof of concept that the IgG subclass composition can be an indicator of the level of RBC alloimmunization as well as discern between primary and secondary immunization at least in this murine model.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Warm autoantibodies (WAAs) cause delays and additional expenses while determining suitable products when using a traditional protocol (TP). In 2013, Carter BloodCare Immunohematology Reference Laboratory (IRL) introduced a molecular protocol (MP) for patients with WAAs.</jats:p></jats:sec><jats:sec><jats:title>Study Design and Methods</jats:title><jats:p>Retrospective review of records for samples referred to the IRL from November 2004 to September 2020, was performed. Referrals, alloantibody(ies), gender, and age were recorded. Additionally, the count of common clinically significant antigens needed for phenotypically matched red blood cells (RBCs) were recorded for patients in MP. To further analyze charges and time spent testing patients with WAAs, 300 patients were selected.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Analysis of average charges to the referring hospital and time spent testing in the IRL determined savings at two or more referrals. Overall, 219 of 300 (73%) of patients in the study met or exceeded the number of referrals. Further analysis shows that while the population of patients with WAA (<jats:italic>n</jats:italic> = 300) shared similar demographics, there was a statistically significant difference between the average time testing patients in TP (<jats:italic>M</jats:italic> = 264.18, <jats:italic>SD</jats:italic> = 15.06) and MP (<jats:italic>M</jats:italic> = 156.00, <jats:italic>SD</jats:italic> = 90.37), <jats:italic>t</jats:italic>(157) = 14.46, <jats:italic>p</jats:italic> &lt; .001, 95% confidence interval [CI] (93.41–122.97). Additionally, the assumption that each patient received two RBCs per referral provided no statistically significant difference between average charges to the hospitals of patients in TP (<jats:italic>M</jats:italic> = 1222.58, <jats:italic>SD</jats:italic> = 165.69) and MP (<jats:italic>M</jats:italic> = 1269.78, <jats:italic>SD</jats:italic> = 433.52), <jats:italic>t</jats:italic>(192) = −1.25, <jats:italic>p</jats:italic> = .214, 95% CI (−121.95–27.54).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The MP has been effective in saving time spent testing patients with WAAs, which benefits referring hospitals, patients, and IRLs. Charges for prophylactic phenotypically matched blood were negligible and a MP would alleviate some of the current laboratory difficulties while providing safe products to patients.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Transfusion‐related acute lung injury (TRALI) is a leading cause of transfusion‐related mortality. A concern with passive surveillance to detect transfusion reactions is underreporting. Our aim was to obtain evidence‐based estimates of TRALI incidence using meta‐analysis of active surveillance studies and to compare these estimates with passive surveillance.</jats:p></jats:sec><jats:sec><jats:title>Study Design and Methods</jats:title><jats:p>We performed a systematic review and meta‐analysis of studies reporting TRALI rates. A search of Medline and Embase by a research librarian identified studies published between January 1, 1991 and January 20, 2023. Prospective and retrospective observational studies reporting TRALI by blood component (red blood cells [RBCs], platelets, or plasma) were identified and all inpatient and outpatient settings were eligible. Adult and pediatric, as well as general and specific clinical populations, were included. Platelets and plasma must have used at least one modern TRALI donor risk mitigation strategy. A random effects model estimated TRALI incidence by blood component for active and passive surveillance studies and heterogeneity was examined using meta‐regression.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Eighty studies were included with approximately 176‐million blood components transfused. RBCs had the highest number of studies (<jats:italic>n</jats:italic> = 66) included, followed by platelets (<jats:italic>n</jats:italic> = 35) and plasma (<jats:italic>n</jats:italic> = 34). Pooled TRALI estimates for active surveillance studies were 0.17/10,000 (95% confidence intervals [CI]: 0.03–0.43; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 79%) for RBCs, 0.31/10,000 (95% CI: 0.22–0.42; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = &lt;1%) for platelets, and 3.19/10,000 (95% CI: 0.09–10.66; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 86%) for plasma. Studies using passive surveillance ranged from 0.02 to 0.10/10,000 among the various blood components.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>In summary, these estimates may improve a quantitative understanding of TRALI risk, which is important for clinical decision‐making weighing the risks and benefits of transfusion.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Study Design and Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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; <jats:italic>p</jats:italic> &lt; .0001) and saved US $100.25 per RBC unit.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>