Transfusions of RBCs stored for longer durations are associated with adverse effects in hospitalized patients. We prospectively studied 14 healthy human volunteers who donated standard leukoreduced, double RBC units. One unit was autologously transfused "fresh" (3-7 days of storage), and the other "older" unit was transfused after 40 to 42 days of storage. Of the routine laboratory parameters measured at defined times surrounding transfusion, significant differences between fresh and older transfusions were only observed in iron parameters and markers of extravascular hemolysis. IntroductionThe safety of transfusing RBCs after longer durations of refrigerated storage was recently identified as "the most critical issue facing transfusion medicine." 1 page 667 Concern was heightened when a large observational study of cardiac surgery patients found an increased risk of postoperative complications and reduced survival in those who received RBCs stored for more than 14 days. 2 Although still controversial, adverse clinical consequences have since been reported in most, [3][4][5] although not all, 6,7 epidemiologic studies of transfusions of RBCs stored for longer durations, but still within Food and Drug Administration (FDA) guidelines. The association between the duration of RBC storage and increased rates of serious infections, sepsis, and mortality is particularly strong in trauma patients. [7][8][9][10][11] Definitive determination of the potential risks associated with transfusion of RBCs stored for longer durations has been elusive, in part because the mechanisms responsible have not yet been identified.More than 14 million RBC units are transfused in the United States each year, with a mean storage interval of 18 days before transfusion. 12 During storage, RBCs undergo cumulative biochemical and biomechanical changes (the "storage lesion") that reduce their survival in vivo after transfusion. 13,14 In mouse models, 15 transfusion of RBCs stored for longer durations was followed by brisk extravascular clearance of a subpopulation of these cells, which were damaged during storage and removed by macrophages in the spleen and liver of recipient mice. The iron liberated by phagocytic digestion of these RBCs rapidly entered the systemic circulation in amounts that exceeded the transport capacity of plasma transferrin, the physiologic iron-binding protein; in this way, circulating non-transferrin-bound iron appeared and promoted the proliferation of pathogenic bacteria both in vitro 15 and in vivo. 16 We hypothesized that the infectious complications observed in human patients after transfusion of RBCs stored for longer durations were, at least in part, the result of the production of circulating non-transferrin-bound iron. Therefore, we prospectively examined healthy human volunteers to determine (1) if transfusion of autologous RBCs stored for longer durations was followed by the appearance of circulating non-transferrin-bound iron in vivo, and (2) if this increased circulating non-transferrinbound iron was assoc...

Background: Although convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited. Objective: To evaluate the clinical efficacy and safety of convalescent plasma among adults hospitalized with severe and critical COVID-19. Design: Randomized, double-blind, controlled, multicenter, phase 2 trial conducted from April 21st to November 27th, 2020. Setting: Five hospitals in New York City (NY, USA) and Rio de Janeiro (Brazil). Participants: Hospitalized patients aged ≥18 years with laboratory-confirmed COVID-19, infiltrates on chest imaging and oxygen saturation ≤ 94% on room air or requirement for supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Intervention: Participants were randomized 2:1 to a single transfusion of either 1 unit of convalescent or normal control plasma. Measurements: The primary outcome was clinical status at 28 days, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population (with an odds ratio (OR) >1.0 indicating improved clinical status in the convalescent plasma group). Results: Of 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to normal control plasma. At 28 days, no significant improvement in clinical status was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval (CI) 0.83-2.68, p=0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, p=0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected. Serious adverse events occurred in 39/147 (27%) participants who received convalescent plasma and 26/72 (36%) participants who received control plasma. Limitations: Some participants did not receive high-titer convalescent plasma. Conclusion: In adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in 28 days clinical status. However, a significant improvement in mortality was observed, which warrants further evaluation. Registration: ClinicalTrials.gov, NCT04359810 Funding: Amazon Foundation

Background: Although convalescent plasma has been widely used to treat severe coronavirus disease 2019 , data from randomized controlled trials that support its efficacy are limited. Methods:We conducted a randomized, double-blind, placebo-controlled trial among adults hospitalized with severe and critical COVID-19 at five sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or placebo (normal control plasma). The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.Results: Of 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval (CI) 0.83-2.68, p=0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, p=0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected. Conclusion:In adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.

BACKGROUND Children are known to be physiologically and biochemically different from adults. However, there are no multi‐institutional studies examining the differences in the frequency, type, and severity of transfusion reactions in pediatric versus adult patients. This study aims to characterize differences between pediatric and adult patients regarding adverse responses to transfusions. STUDY DESIGN AND METHODS This is a retrospective data analysis of nine children's hospitals and 35 adult hospitals from January 2009 through December 2015. Included were pediatric and adult patients who had a reported reaction to transfusion of any blood component. Rates are reported as per 100,000 transfusions for comparison between pediatric and adult patients. RESULTS Pediatric patients had an overall higher reaction rate compared to adults: 538 versus 252 per 100,000 transfusions, notably higher for red blood cell (577 vs. 278 per 100,000; p < 0.001) and platelet (833 vs. 358 per 100,000; p < 0.001) transfusions. Statistically higher rates of allergic reactions, febrile nonhemolytic reactions, and acute hemolytic reactions were observed in pediatric patients. Adults had a higher rate of delayed serologic transfusion reactions, delayed hemolytic transfusion reactions, and transfusion‐associated circulatory overload. CONCLUSION Pediatric patients had double the rate of transfusion reactions compared to adults. The nationally reported data on reaction rates are consistent with this study's findings in adults but much lower than the observed rates for pediatric patients. Future studies are needed to address the differences in reaction rates, particularly in allergic and febrile reactions, and to further address blood transfusion practices in the pediatric patient population.