Abstract

BACKGROUND Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited. METHODS In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group. RESULTS A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06). CONCLUSIONS This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).

Abstract

OBJECTIVES Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia. METHODS Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist. RESULTS Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%). CONCLUSIONS Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.

Abstract

BACKGROUND AND OBJECTIVES Platelet transfusions are used across multiple patient populations to prevent and correct bleeding. This scoping review aimed to map the currently available systematic reviews (SRs) and evidence-based guidelines in the field of platelet transfusion. MATERIALS AND METHODS A systematic literature search was conducted in seven databases for SRs on effectiveness (including dose and timing, transfusion trigger and ratio to other blood products), production modalities and decision support related to platelet transfusion. The following data were charted: methodological features of the SR, population, concept and context features, outcomes reported, study design and number of studies included. Results were synthesized in interactive evidence maps. RESULTS We identified 110 SRs. The majority focused on clinical effectiveness, including prophylactic or therapeutic transfusions compared to no platelet transfusion (34 SRs), prophylactic compared to therapeutic-only transfusion (8 SRs), dose, timing (11 SRs) and threshold for platelet transfusion (15 SRs) and the ratio of platelet transfusion to other blood products in massive transfusion (14 SRs). Furthermore, we included 34 SRs on decision support, of which 26 evaluated viscoelastic testing. Finally, we identified 22 SRs on platelet production modalities, including derivation (4 SRs), pathogen inactivation (6 SRs), leucodepletion (4 SRs) and ABO/human leucocyte antigen matching (5 SRs). The SRs were mapped according to concept and clinical context. CONCLUSION An interactive evidence map of SRs and evidence-based guidelines in the field of platelet transfusion has been developed and identified multiple reviews. This work serves as a tool for researchers looking for evidence gaps, thereby both supporting research and avoiding unnecessary duplication.

Abstract

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

Abstract

AIM: To characterize the association between diabetes and transfusion and clinical outcomes in cardiac surgery, and to evaluate whether restrictive transfusion thresholds are harmful in these patients. MATERIALS AND METHODS The multinational, open-label, randomized controlled TRICS-III trial assessed a restrictive transfusion strategy (hemoglobin [Hb] transfusion threshold <75 g/L) compared to a liberal strategy (Hb <95 g/L for operating room or ICU; or < 85 g/L for ward) in patients undergoing cardiac surgery on cardiopulmonary bypass with a moderate-to-high risk of death (EuroSCORE ≥6). Diabetes status was collected preoperatively. The primary composite outcome was all-cause death, stroke, myocardial infarction, and new-onset renal failure requiring dialysis at 6 months. Secondary outcomes included components of the composite outcome at 6 months, and transfusion and clinical outcomes at 28 days. RESULTS Of the 5092 patients analyzed, 1396 (27.4%) had diabetes (Restrictive: n = 679, Liberal n = 717). Patients with diabetes had more cardiovascular disease than patients without diabetes. Neither the presence of diabetes (OR [95%CI]1.10[0.93-1.31]) or the restrictive strategy increased the risk for the primary composite outcome (diabetes OR [95%CI]1.04[0.68-1.59] vs. no diabetes OR 1.02[0.85-1.22],p(interaction) = 0.92). In patients with versus without diabetes, a restrictive transfusion strategy was more effective at reducing red blood cell transfusion (diabetes OR [95%CI] 0.28[0.21-0.36]; no diabetes OR [95%CI] 0.40[0.35-0.47];p(interaction) = 0.04). CONCLUSIONS The presence of diabetes did not modify the effect of a restrictive transfusion strategy on the primary composite outcome, but improved its efficacy on red cell transfusion. Restrictive transfusion triggers are safe and effective in patients with diabetes undergoing cardiac surgery. This article is protected by copyright. All rights reserved.

Abstract

BACKGROUND Guidelines for platelet (PLT) transfusion are an important source of information for clinicians. Although guidelines intend to increase consistency and quality of care, variation in methodology and recommendations may exist that could impact the value of a guideline. We aimed to determine the quality of existing PLT transfusion guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument and to describe the inconsistencies in recommendations. STUDY DESIGN AND METHODS A systematic search was undertaken for evidence-based guidelines from January 1, 2013, to January 25, 2019. Citations were reviewed in duplicate for inclusion and descriptive data extracted. Four physicians appraised the guideline using the AGREE II instrument and the scaled score for each item evaluated was calculated. The protocol was registered in PROSPERO. RESULTS Of 6744 citations, 6740 records were screened. Seven of 28 full-text studies met the inclusion criteria. The median scaled score (and the interquartile range of the scaled score) for the following items were as follows: scope and purpose, 94% (8%); stakeholder involvement, 63% (18%); rigor of development, 83% (14%); clarity of presentation, 94% (6%); applicability, 58% (20%); and editorial independence, 77% (4%). Overall quality ranged from 4 to 7 (7 is the maximum score). Inconsistent recommendations were on prophylactic PLT transfusion in hypoproliferative thrombocytopenia in the presence of risk factors and dose recommendations. CONCLUSION Inconsistencies between guidelines and variable quality highlight areas for future guideline writers to address. Areas of specific attention include issues of stakeholder involvement and applicability.

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.

Abstract

The COVID-19 pandemic has major implications for blood transfusion. There are uncertain patterns of demand, and transfusion institutions need to plan for reductions in donations and loss of crucial staff because of sickness and public health restrictions. We systematically searched for relevant studies addressing the transfusion chain-from donor, through collection and processing, to patients-to provide a synthesis of the published literature and guidance during times of potential or actual shortage. A reduction in donor numbers has largely been matched by reductions in demand for transfusion. Contingency planning includes prioritisation policies for patients in the event of predicted shortage. A range of strategies maintain ongoing equitable access to blood for transfusion during the pandemic, in addition to providing new therapies such as convalescent plasma. Sharing experience and developing expert consensus on the basis of evolving publications will help transfusion services and hospitals in countries at different stages in the pandemic.

Abstract

PURPOSE Iron restricted anemia is prevalent in surgical patients and is associated with an increased risk of allogeneic red blood cell (RBC) transfusion and adverse events. Treatment of anemia includes oral and intravenous iron and erythropoiesis stimulating agents (ESAs). More recent studies have focused on the use of intravenous iron as the primary approach to treating anemia. Nevertheless, the optimal treatment strategy for anemia remains to be established. Our primary objective was to evaluate the efficacy and safety of ESA and iron therapy relative to iron therapy alone in reducing RBC transfusion in surgical patients. SOURCE We searched the Cochrane Library, MEDLINE, EMBASE, and ClinicalTrials.gov from inception to May 2018. We included randomized-controlled trials in which adult surgical patients received an ESA and iron, vs iron alone, prior to cardiac and non-cardiac surgery. Our primary outcome was RBC transfusion rate. Secondary outcomes included hemoglobin concentration (post-treatment and postoperatively), number of RBC units transfused, mortality, stroke, myocardial infarction (MI), renal dysfunction, pulmonary embolism (PE), and deep vein thrombosis (DVT). PRINCIPAL FINDINGS In total, 25 studies (4,719 participants) were included. Erythropoiesis stimulating agents and iron therapy reduced RBC transfusion relative to iron therapy (relative risk [RR] 0.57; 95% confidence interval [CI], 0.46 to 0.71) without any change in mortality (RR 1.31; 95% CI, 0.80 to 2.16), stroke (RR 1.91; 95% CI, 0.63 to 5.76), MI (RR 1.12; 95% CI, 0.50 to 2.50), renal dysfunction (RR 0.96; 95% CI, 0.72 to 1.26), PE (RR 0.92; 95% CI, 0.15 to 5.83), or DVT (RR 1.48; 95% CI, 0.95 to 2.31). CONCLUSION Administration of ESA and iron therapy reduced the risk for RBC transfusion compared with iron therapy alone in patients undergoing cardiac and non-cardiac surgery. Nevertheless, publication bias and heterogeneity reduces the confidence of the finding. Although the analysis was probably under-powered for some outcomes, no difference in the incidence of serious adverse events was observed with ESA and iron compared with iron alone. Further large prospective trials are required to confirm these findings.

Abstract

BACKGROUND Safely reducing red blood cell transfusions can prevent transfusion-related adverse effects, conserve the blood supply, and reduce health care costs. Both anemia and red blood cell transfusion are independently associated with AKI, but observational data are insufficient to determine whether a restrictive approach to transfusion can be used without increasing AKI risk. METHODS In a prespecified kidney substudy of a randomized noninferiority trial, we compared a restrictive threshold for red blood cell transfusion (transfuse if hemoglobin<7.5 g/dl, intraoperatively and postoperatively) with a liberal threshold (transfuse if hemoglobin<9.5 g/dl in the operating room or intensive care unit, or if hemoglobin<8.5 g/dl on the nonintensive care ward). We studied 4531 patients undergoing cardiac surgery with cardiopulmonary bypass who had a moderate-to-high risk of perioperative death. The substudy's primary outcome was AKI, defined as a postoperative increase in serum creatinine of ≥0.3 mg/dl within 48 hours of surgery, or ≥50% within 7 days of surgery. RESULTS Patients in the restrictive-threshold group received significantly fewer transfusions than patients in the liberal-threshold group (1.8 versus 2.9 on average, or 38% fewer transfusions in the restricted-threshold group compared with the liberal-threshold group; P<0.001). AKI occurred in 27.7% of patients in the restrictive-threshold group (624 of 2251) and in 27.9% of patients in the liberal-threshold group (636 of 2280). Similarly, among patients with preoperative CKD, AKI occurred in 33.6% of patients in the restrictive-threshold group (258 of 767) and in 32.5% of patients in the liberal-threshold group (252 of 775). CONCLUSIONS Among patients undergoing cardiac surgery, a restrictive transfusion approach resulted in fewer red blood cell transfusions without increasing the risk of AKI.