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1.
Length of red blood cell storage and clinical outcomes in transfused critical ill adults – the Age of Blood Evaluation (ABLE) randomised controlled trial
Lacroix L, Hebert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall, JC, Clayton L, McIntyre L, Callum J, et al
Transfusion Medicine. 2015;25((Suppl. 1)):6.. Abstract No. S10
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2.
Effects of red-cell storage duration on patients undergoing cardiac surgery
Steiner ME, Ness PM, Assmann SF, Triulzi DJ, Sloan SR, Delaney M, Granger S, Bennett-Guerrero E, Blajchman MA, Scavo V, et al
New England Journal of Medicine. 2015;372((15):):1419-29.
Abstract
BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion.METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge.RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group.CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).
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3.
Age of transfused blood in critically ill adults
Lacroix J, Hebert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, Clayton L, McIntyre L, Callum J, Turgeon AF, et al
New England Journal of Medicine. 2015;372((15):):1410-8.
Abstract
BACKGROUND Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (+/-SD) of 6.1+/-4.9 days in the fresh-blood group as compared with 22.0+/-8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).
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4.
Randomized trial results: red cell storage age is not associated with a significant difference in multiple-organ dysfunction score or mortality in transfused cardiac surgery patients
Steiner ME, Triulzi DJ, Assmann SF, Sloan SR, Delaney M, Blajchman MA, Granger S, D'Andrea PA, Pulkrabek S, Stowell CP
Transfusion. 2014;54((S2)):15A.. Abstract No. P2-030A.
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5.
Age of red blood cells in premature infants (ARIPI)
Fergusson DA, Hebert PC, LeBel L, Rouvinez-Bouali NG, Smyth JA, Sankaran K, Tinmouth AT, Blajchman MA, Kovacs L, Lachance C
Transfusion. 2012;52((S3)):11A-12A.. Abstract No. P3-030A.
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6.
Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial
Fergusson DA, Hébert P, Hogan DL, LeBel L, Rouvinez-Bouali N, Smyth JA, Sankaran K, Tinmouth A, Blajchman MA, Kovacs L, et al
JAMA: the Journal of the American Medical Association. 2012;308((14):):1443-51.
Abstract
CONTEXT Even though red blood cells (RBCs) are lifesaving in neonatal intensivecare, transfusing older RBCs may result in higher rates of organ dysfunction,nosocomial infection, and length of hospital stay. OBJECTIVE To determine if RBCs stored for 7 days or less compared with usual standards decreased rates ofmajor nosocomial infection and organ dysfunction in neonatal intensive care unitpatients requiring at least 1 RBC transfusion. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized controlled trial in 377 premature infants with birthweights less than 1250 g admitted to 6 Canadian tertiary neonatal intensive careunits between May 2006 and June 2011. INTERVENTION Patients were randomlyassigned to receive transfusion of RBCs stored 7 days or less (n = 188) vsstandard-issue RBCs in accordance with standard blood bank practice (n = 189). MAIN OUTCOME MEASURES The primary outcome was a composite measure of majorneonatal morbidities, including necrotizing enterocolitis, retinopathy ofprematurity, bronchopulmonary dysplasia, and intraventricular hemorrhage, as wellas death. The primary outcome was measured within the entire period of neonatalintensive care unit stay up to 90 days after randomization. The rate ofnosocomial infection was a secondary outcome. RESULTS The mean age of transfusedblood was 5.1 (SD, 2.0) days in the fresh RBC group and 14.6 (SD, 8.3) days inthe standard group. Among neonates in the fresh RBC group, 99 (52.7%) had theprimary outcome compared with 100 (52.9%) in the standard RBC group (relativerisk, 1.00; 95% CI, 0.82-1.21). The rate of clinically suspected infection in thefresh RBC group was 77.7% (n = 146) compared with 77.2% (n = 146) in the standardRBC group (relative risk, 1.01; 95% CI, 0.90-1.12), and the rate of positivecultures was 67.5% (n = 127) in the fresh RBC group compared with 64.0% (n = 121)in the standard RBC group (relative risk, 1.06; 95% CI, 0.91-1.22). CONCLUSION In this trial, the use of fresh RBCs compared with standard blood bank practicedid not improve outcomes in premature, very low-birth-weight infants requiring atransfusion. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00326924;Current Controlled Trials Identifier: ISRCTN65939658.
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7.
The Age of Blood Evaluation (ABLE) randomized controlled trial: study design
Lacroix J, Hebert P, Fergusson D, Tinmouth A, Blajchman MA, Callum J, Cook D, Marshall JC, McIntyre L, Turgeon AF
Transfusion Medicine Reviews. 2011;25((3):):197-205.
Abstract
Red blood cells (RBCs) are transfused to treat anemia and to maintain oxygen delivery to vital organs during critical illness. Laboratory and observational studies have raised the possibility that prolonged RBC storage may adversely affect clinical outcomes. Compared with RBCs stored less than 1 week, there are no clinical data demonstrating that RBCs stored longer remain as effective at carrying or releasing oxygen, and observational studies have risen to possibility that prolonged RBC storage might result in harm to vulnerable patients requiring blood transfusions. The Age of Blood Evaluation(ABLE) study (ISRCTN44878718) is a double-blind, multicenter, parallel randomized controlled clinical trial. It will test the hypothesis that the transfusion of prestorage leukoreduced RBCs stored for 7 days or less (fresh arm) as compared with standard-issue RBCs stored, on average, 15 to 20 days (control arm) will lead to lower 90-day all-cause mortality and reduced morbidity in critically ill adults. We include adults in intensive care units (ICUs) who (1) have had a request for a first RBC unit transfusion during the first 7 days of ICU admission and (2) have an anticipated requirement for ongoing invasive and noninvasive mechanical ventilation exceeding 48 hours. Enrolled patients are randomized at the time of transfusion to receive either standard-issue RBC units or RBCs stored 7 days or less issued by the local hospital transfusion service. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, organ failure, and serious nosocomial infections. With 2510 patients, we will be able to detect a 5% absolute risk reduction (from 25% to 20%). The ABLE study is currently enrolling patients in 23 university-affiliated and community-hospital ICUs across Canada; sites in France and United Kingdom are expected to start recruitment in 2011. Regardless of the results, ABLE study will have significant implications on the duration of RBC storage. A negative trial will reassure clinicians and blood bankers regarding the effectiveness and safety of standard-issue RBCs. A positive trial will have significant implications with respect to inventory management of RBCs given to critically ill adults with a high risk of mortality and will also prompt research to better understand the RBC storage lesion in the hopes of minimizing its clinical consequences through the development of better storage methods.
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8.
The age of red blood cells in premature infants (ARIPI) randomized controlled trial: study design
Fergusson D, Hutton B, Hogan DL, LeBel L, Blajchman MA, Ford JC, Hebert P, Kakadekar A, Kovacs L, Lee S, et al
Transfusion Medicine Reviews. 2009;23((1):):55-61.
Abstract
Despite recent trends in decreasing transfusion thresholds and the development of technologies designed to avoid allogeneic exposure, allogeneic red blood cell (RBC) transfusions remain an important supportive and life-saving measure for neonatal intensive care patients experiencing illness and anemia. Reluctantly, a number of laboratory and observational studies have indicated that the amount of time RBCs are stored can affect oxygen delivery to tissues. Consequently, older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and lengths of stay. Because of such harmful effects, an evaluation of the association between age of blood and nosocomial infection and organ dysfunction is warranted. The aim of the study was to determine if RBCs stored for 7 days or less (fresh RBCs) compared to current standard transfusion practice decreases major nosocomial infection and organ dysfunction in neonates admitted to the neonatal intensive care unit and requiring at least one RBC transfusion. This study is a double-blind, multicenter, randomized controlled trial design. The trial will be an effectiveness study evaluating the effectiveness of stored vs fresh RBCs in neonates requiring transfusion. Neonatal patients requiring at least one unit of RBCs will be randomized to receive either (1) RBCs stored no longer than 7 days or (2) standard practice. The study was conducted in Canadian university-affiliated level III (tertiary) neonatal intensive care units. The primary outcome for this study will be a composite measure of major neonatal morbidities (necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, and mortality). Secondary outcomes include individual items of the composite measure and nosocomial infection (bacteremia, septic shock, and pneumonia). The sample size calculations have been estimated based on the formula for 2 independent proportions using an alpha of . 05, a (1-beta) of . 80, and a 10% noncompliance factor. The baseline rate for our composite measure is estimated to be 65% as indicated by the literature. Assuming a 15% absolute risk reduction with the use of RBCs stored 7 days or less, our estimated total sample size required will be 450 (225 patients per treatment arm). The Age of Red Blood Cells in Premature Infants (ARIPI) trial is registered at the US National Institutes of Health (ClinicalTrials. gov) no. NCT00326924 and current controlled trials ISRCTN65939658.
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9.
A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation
Webert KE, Cook RJ, Couban S, Carruthers J, Lee KA, Blajchman MA, Lipton JH, Brandwein JM, Heddle NM
Transfusion. 2008;48((1):):81-91.
Abstract
BACKGROUND Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia. STUDY DESIGN AND METHODS A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L). RESULTS Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0. 233 vs. 0. 151; relative risk, 1. 56; 95% confidence interval, 1. 16-2. 10; p = 0. 003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented. CONCLUSION This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients.
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10.
A comparison of aprotinin and lysine analogues in high-risk cardiac surgery
Fergusson DA, Hébert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, Teoh K, Duke PC, Arellano R, Blajchman MA, et al
The New England Journal of Medicine. 2008;358((22):):2319-31.
Abstract
BACKGROUND Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences. METHODS In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days. RESULTS The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9. 5%) in the aprotinin group had massive bleeding, as compared with 93 (12. 1%) in the tranexamic acid group and 94 (12. 1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0. 79; 95% confidence interval [CI], 0. 59 to 1. 05). At 30 days, the rate of death from any cause was 6. 0% in the aprotinin group, as compared with 3. 9% in the tranexamic acid group (relative risk, 1. 55; 95% CI, 0. 99 to 2. 42) and 4. 0% in the aminocaproic acid group (relative risk, 1. 52; 95% CI, 0. 98 to 2. 36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1. 53 (95% CI, 1. 06 to 2. 22). CONCLUSIONS Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials. com]. ).