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Practice patterns of ABO-matching for cryoprecipitate and patient outcomes after ABO-compatible versus incompatible cryoprecipitate
Raycraft T, Bartoszko J, Karkouti K, Callum J, Lin Y
Vox sanguinis. 2022
Abstract
BACKGROUND AND OBJECTIVES This sub-study of the FIBRES trial sought to examine the patterns of ABO-compatible cryoprecipitate administration and to identify adverse consequences of ABO-incompatible cryoprecipitate. MATERIALS AND METHODS This was a post hoc analysis of data collected from the FIBRES randomized clinical trial comparing fibrinogen concentrate with cryoprecipitate in the treatment of bleeding related to hypofibrinogenemia after cardiac surgery. The primary outcome was the percentage of administered cryoprecipitate that was ABO-compatible. Secondary outcomes were adverse events at 28 days. A follow-up survey was distributed to the FIBRES participating sites to examine the rationale behind the identified cryoprecipitate ABO-matching practice patterns. RESULTS A total of 363 patients were included: 53 (15%) received ABO-incompatible cryoprecipitate and 310 (85%) received ABO-compatible cryoprecipitate. There was an increased incidence of post-operative anaemia in the ABO-incompatible group (15; 28.3%) in comparison to the ABO-compatible (44; 14.2%) group (p = 0.01) at 28 days, which was unrelated to haemolysis, without a significant difference in transfusion requirement. In the multivariable logistic regression models accounting for clustering by site, there was no observed statistically significant association between the administration of ABO-incompatible cryoprecipitate and any other adverse outcomes. Nine out of 11 sites did not have a policy requiring ABO-matched cryoprecipitate. CONCLUSION This sub-study demonstrated that most cryoprecipitate administered in practice is ABO-compatible, despite the absence of guidelines or blood bank policies to support this practice. A signal towards increased risk of post-operative anaemia may be explained by higher rates of urgent surgery (vs. elective) in the ABO-incompatible group. Future studies should prospectively examine the impact of ABO-compatible versus incompatible cryoprecipitate to conclusively establish if there is a meaningful clinical impact associated with the administration of ABO-incompatible cryoprecipitate.
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A data-informed system to manage scarce blood product allocation in a randomized controlled trial of convalescent plasma
Li N, Zeller MP, Shih AW, Heddle NM, St John M, Bégin P, Callum J, Arnold DM, Akbari-Moghaddam M, Down DG, et al
Transfusion. 2022
Abstract
BACKGROUND Equitable allocation of scarce blood products needed for a randomized controlled trial (RCT) is a complex decision-making process within the blood supply chain. Strategies to improve resource allocation in this setting are lacking. METHODS We designed a custom-made, computerized system to manage the inventory and allocation of COVID-19 convalescent plasma (CCP) in a multi-site RCT, CONCOR-1. A hub-and-spoke distribution model enabled real-time inventory monitoring and assignment for randomization. A live CCP inventory system using REDCap was programmed for spoke sites to reserve, assign, and order CCP from hospital hubs. A data-driven mixed-integer programming model with supply and demand forecasting was developed to guide the equitable allocation of CCP at hubs across Canada (excluding Québec). RESULTS 18/38 hospital study sites were hubs with a median of 2 spoke sites per hub. A total of 394.5 500-ml doses of CCP were distributed; 349.5 (88.6%) doses were transfused; 9.5 (2.4%) were wasted due to mechanical damage sustained to the blood bags; 35.5 (9.0%) were unused at the end of the trial. Due to supply shortages, 53/394.5 (13.4%) doses were imported from Héma-Québec to Canadian Blood Services (CBS), and 125 (31.7%) were transferred between CBS regional distribution centers to meet demand. 137/349.5 (39.2%) and 212.5 (60.8%) doses were transfused at hubs and spoke sites, respectively. The mean percentages of total unmet demand were similar across the hubs, indicating equitable allocation, using our model. CONCLUSION Computerized tools can provide efficient and immediate solutions for equitable allocation decisions of scarce blood products in RCTs.
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Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial
Bégin P, Callum J, Jamula E, Cook R, Heddle NM, Tinmouth A, Zeller MP, Beaudoin-Bussières G, Amorim L, Bazin R, et al
Nature Medicine. 2021
Abstract
The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
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Red cell transfusion in outpatients with myelodysplastic syndromes: a feasibility and exploratory randomised trial
Stanworth SJ, Killick S, McQuilten ZK, Karakantza M, Weinkove R, Smethurst H, Pankhurst LA, Hodge RL, Hopkins V, Thomas HL, et al
British journal of haematology. 2020
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Abstract
Optimal red cell transfusion support in myelodysplastic syndromes (MDS) has not been tested and established. The aim of this study was to demonstrate feasibility of recruitment and follow-up in an outpatient setting with an exploratory assessment of quality of life (QoL) outcomes (EORTC QLQ-C30 and EQ-5D-5L). We randomised MDS patients to standardised transfusion algorithms comparing current restrictive transfusion thresholds (80 g/l, to maintain haemoglobin 85-100 g/l) with liberal thresholds (105 g/l, maintaining 110-125 g/l). The primary outcomes were measures of compliance to transfusion thresholds. Altogether 38 patients were randomised (n = 20 restrictive; n = 18 liberal) from 12 participating sites in UK, Australia and New Zealand. The compliance proportion for the intention-to-treat population was 86% (95% confidence interval 75-94%) and 99% (95-100%) for restrictive and liberal arms respectively. Mean pre-transfusion haemoglobin concentrations for restrictive and liberal arms were 80 g/l (SD6) and 97 g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm. Our findings support the feasibility and need for a definitive trial to evaluate the effect of different red cell transfusion thresholds on patient-centred outcomes.
PICO Summary
Population
Patients with myelodysplastic syndrome, (n=38).
Intervention
Restrictive transfusion threshold (80 g/l, to maintain haemoglobin 85-100 g/l), (n=20).
Comparison
Liberal transfusion threshold (105 g/l, to maintain haemoglobin 110-125 g/l), (n=18).
Outcome
The compliance proportion for the intention-to-treat population was 86% and 99% for restrictive and liberal arms respectively. Mean pre-transfusion haemoglobin concentrations for restrictive and liberal arms were 80 g/l (SD6) and 97 g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm.
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Adverse effects of red blood cell transfusions in neonates: a systematic review and meta-analysis
Keir A, Pal S, Trivella M, Lieberman L, Callum J, Shehata N, Stanworth SJ
Transfusion. 2016;56((11):):2773-2780
Abstract
BACKGROUND Controversy exists regarding the contribution of blood transfusions to a range of adverse clinical outcomes in neonates. The aim of our systematic review was to identify the broader literature on harmful effects and associations potentially attributable to red blood cell (RBC) transfusions. STUDY DESIGN AND METHODS A comprehensive search of MEDLINE (PubMed) and EMBASE was undertaken. Eligible studies included both randomized controlled trials (RCTs) and nonrandomized studies examining the effects of small volume (10-20 mL/kg) RBC transfusions on neonates. Primary outcomes of interest were mortality, chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. Two independent authors conducted a review of abstracts and then of full-text article reviews as well as data extraction and quality assessments. RESULTS Sixty-one studies were eligible for inclusion, including 16 (26%) randomized studies. The majority of studies were nonrandomized (n = 45; 74%), which included 32 observational studies with and 13 studies without a comparator group. There was no evidence that rates of mortality differed between restrictive and liberal strategies for transfusion (eight RCTs: risk ratio, 1.24; 95% confidence interval, 0.89-1.672, heterogeneity = 0%) or for necrotizing enterocolitis (five RCTs: risk ratio, 1.45; 95% confidence interval, 0.91-2.33; heterogeneity = 0%). A liberal strategy also was not superior to restrictive transfusion practice in the pooled randomized studies for rates of retinopathy of prematurity, chronic lung disease, or intraventricular hemorrhage. CONCLUSIONS Statistically significant differences in a range of harmful outcomes between neonates exposed to restrictive and liberal RBC transfusion practice were not found. However, the risks of bias identified in many studies and the lack of consistent reporting and definitions of events limits our conclusions.
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A systematic review and meta-analysis of risks of red cell transfusion for neonatal morbidities or mortality
Keir AK, Pal S, Trivella M, Lieberman L, Callum J, Shehata N, Stanworth S
Vox Sanguinis. 2015;109((Suppl. 1)):31-32.. Abstract No. 3D-S12-02.
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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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Adverse effects of RBC transfusions in neonates: a systematic review and meta-analysis
Keir A, Pal S, Trivella M, Lieberman L, Callum J, Sheheta N, Stanworth S
Abstracts of the HAA 2015 Annual Scientific Meeting. 2015;:196-7.. Abstract No. 151.
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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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Adverse effects of small-volume red blood cell transfusions in the neonatal population
Keir A, Pal S, Trivella M, Lieberman L, Callum J, Shehata N, Stanworth S
Systems Review. 2014;3((1):):92.
Abstract
BACKGROUND Adverse transfusion reactions in the neonatal population are poorly understood and defined. The incidence and pattern of adverse effects due to red blood cell (RBC) transfusion are not well known, and there has been no systematic review of published adverse events. RBC transfusions continue to be linked to the development of morbidities unique to neonates, including chronic lung disease, retinopathy of prematurity, intraventricular haemorrhage and necrotising enterocolitis. Uncertainties about the exact nature of risks alongside benefits of RBC transfusion may contribute to evidence of widespread variation in neonatal RBC transfusion practice.Our review aims to describe clinical adverse effects attributed to small-volume (10-20 mL/kg) RBC transfusions and, where possible, their incidence rates in the neonatal population through the systematic identification of all relevant studies. METHODS A comprehensive search of the following bibliographic databases will be performed: MEDLINE (PubMed/OVID which includes the Cochrane Library) and EMBASE (OVID). The intervention of interest is small-volume (10-20 mL/kg) RBC transfusions in the neonatal population.We will undertake a narrative synthesis of the evidence. If clinical similarity and data quantity and quality permit, we will also carry out meta-analyses on the listed outcomes. DISCUSSION This systematic review will identify and synthesise the reported adverse effects and associations of RBC transfusions in the neonatal population. We believe that this systematic review is timely and will make a valuable contribution to highlight an existing research gap. TRIAL REGISTRATION PROSPERO, CRD42013005107http://www.crd.york.ac.uk/PROSPERO/display_record.asp? ID=CRD42013005107.