Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders.
ABSTRACT: BACKGROUND:Bone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a disease of the elderly, with many elderly people managed conservatively with regular allogeneic red blood cell (RBC) transfusions to treat their anaemia. However, RBC transfusions are not without risk. Despite regular transfusions playing a central role in treating such patients, the optimal RBC transfusion strategy (restrictive versus liberal) is currently unclear. OBJECTIVES:To assess the efficacy and safety of a restrictive versus liberal red blood cell transfusion strategy for patients with myelodysplasia, acquired aplastic anaemia, and other inherited bone marrow failure disorders. SEARCH METHODS:We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (from 1946), Ovid EMBASE (from 1974), EBSCO CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 26th May 2015. SELECTION CRITERIA:RCTs including patients with long-term bone marrow failure disorders that require allogeneic blood transfusion, who are not being actively treated with a haematopoietic stem cell transplant, or intensive chemotherapy. DATA COLLECTION AND ANALYSIS:We used standard Cochrane review methodology. One author initially screened all references, and excluded any that were clearly irrelevant or duplicates. Two authors then independently screened all abstracts of articles, identified by the review search strategy, for relevancy. Two authors independently assessed the full text of all potentially relevant articles for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. MAIN RESULTS:We included one trial (13 participants) and identified three ongoing trials that assess RBC transfusion strategies in people with MDS.The quality of the evidence was very low across different outcomes according to GRADE methodology.The one included study randomised participants to a restrictive [haemoglobin (Hb) transfusion trigger < 72 g/L, 8 participants] or liberal [Hb trigger < 96 g/L, 5 participants] transfusion policy. There was insufficient evidence to determine a difference in all-cause mortality (1 RCT; 13 participants; RR 0.13, 95% CI 0.01 to 2.32; very low quality evidence). There was insufficient evidence to determine a difference in the number of red blood cell transfusions (1 RCT; 13 participants; 1.8 units per patient per month in the liberal group, compared to 0.8 in the restrictive arm, no standard deviation was reported; very low quality evidence). There were no anaemia-related complications reported (cardiac failure) and no reported effect on activity levels (no statistics provided). The study did not report: mortality due to bleeding/infection/transfusion reactions or iron overload, quality of life, frequency and length of hospital admissions, serious infections (requiring admission to hospital), or serious bleeding (e.g. WHO/CTCAE grade 3 (or equivalent) or above). AUTHORS' CONCLUSIONS:This review indicates that there is currently a lack of evidence for the recommendation of a particular transfusion strategy for bone marrow failure patients undergoing supportive treatment only. The one RCT included in this review was only published as an abstract and contained only 13 participants. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients, particularly as the incidence of the main group of bone marrow failure disorders, MDS, rises with an ageing population.
Project description:Hip fracture (HF) in frail elderly patients is associated with poor physical recovery and death. There is often postoperative blood loss and the hemoglobin (Hb) threshold for red blood cell (RBC) transfusions in these patients is unknown. We investigated whether RBC transfusion strategies were associated with the degree of physical recovery or with reduced mortality after HF surgery.We enrolled 284 consecutive post-surgical HF patients (aged ? 65 years) with Hb levels < 11.3 g/dL (7 mmol/L) who had been admitted from nursing homes or sheltered housing. Allocation was stratified by residence. The patients were randomly assigned to either restrictive (Hb < 9.7 g/dL; < 6 mmol/L) or liberal (Hb < 11.3 g/dL; < 7 mmol/L) RBC transfusions given within the first 30 days postoperatively. Follow-up was at 90 days.No statistically significant differences were found in repeated measures of daily living activities or in 90-day mortality rate between the restrictive group (where 27% died) and the liberal group (where 21% died). Per-protocol 30-day mortality was higher with the restrictive strategy (hazard ratio (HR) = 2.4, 95% CI: 1.1-5.2; p = 0.03). The 90-day mortality rate was higher for nursing home residents in the restrictive transfusion group (36%) than for those in the liberal group (20%) (HR = 2.0, 95% CI: 1.1-3.6; p = 0.01).According to our Hb thresholds, recovery from physical disabilities in frail elderly hip fracture patients was similar after a restrictive RBC transfusion strategy and after a liberal strategy. Implementation of a liberal RBC transfusion strategy in nursing home residents has the potential to increase survival.
Project description:BACKGROUND:Anemia is frequent among patients with traumatic brain injury (TBI) and is associated with an increased risk of poor outcome. The optimal hemoglobin concentration to trigger red blood cell (RBC) transfusion in patients with TBI is not clearly defined. METHODS:All eligible consecutive adult patients admitted to the intensive care unit (ICU) with moderate or severe TBI were randomized to a "restrictive" (hemoglobin transfusion threshold of 7?g/dL), or a "liberal" (threshold 9?g/dL) transfusion strategy. The transfusion strategy was continued for up to 14?days or until ICU discharge. The primary outcome was the mean difference in hemoglobin between groups. Secondary outcomes included transfusion requirements, intracranial pressure management, cerebral hemodynamics, length of stay, mortality and 6-month neurological outcome. RESULTS:A total of 44 patients were randomized, 21 patients to the liberal group and 23 to the restrictive group. There were no baseline differences between the groups. The mean hemoglobin concentrations during the 14-day period were 8.4?±?1.0 and 9.3?±?1.3 (p?<?0.01) in the restrictive and liberal groups, respectively. Fewer RBC units were administered in the restrictive than in the liberal group (35 vs. 66, p?=?0.02). There was negative correlation (r?=?-?0.265, p?<?0.01) between hemoglobin concentration and middle cerebral artery flow velocity as evaluated by transcranial Doppler ultrasound and the incidence of post-traumatic vasospasm was significantly lower in the liberal strategy group (4/21, 3% vs. 15/23, 65%; p?<?0.01). Hospital mortality was higher in the restrictive than in the liberal group (7/23 vs. 1/21; p?=?0.048) and the liberal group tended to have a better neurological status at 6?months (p?=?0.06). CONCLUSIONS:The trial reached feasibility criteria. The restrictive group had lower hemoglobin concentrations and received fewer RBC transfusions. Hospital mortality was lower and neurological status at 6 months favored the liberal group. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02203292 . Registered on 29 July 2014.
Project description:BACKGROUND:Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. METHODS:The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (? 70?years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ?9?g/dl during surgery or within 3?days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb???9?g/dl with a target range for the post-transfusion Hb level of 9-10.5?g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb???7.5?g/dl with a target range for the post-transfusion Hb level of 7.5-9?g/dl). The intervention per patient will be followed until hospital discharge or up to 30?days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90?days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. DISCUSSION:The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90?days after surgery. TRIAL REGISTRATION:ClinicalTrials.gov (identifier: NCT03369210 ).
Project description:INTRODUCTION:Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ?100?g/L), comparing a liberal transfusion strategy (Hb ?100?g/L) with a restrictive strategy (Hb ?80?g/L) on the combined rate of death and severe disability at 12?months. METHODS:Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14?days of their initial bleed and with anaemia (Hb ?110?g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ?100?g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ?100?g/L) or a restrictive transfusion strategy (threshold: Hb ?80?g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12?months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12?months. Outcome measures will be reported in aggregate. ETHICS AND DISSEMINATION:The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. TRIAL REGISTRATION NUMBER:NCT02483351; Pre-results.
Project description:OBJECTIVE:To address the significant uncertainty as to whether transfusion thresholds for critical care versus surgical patients should differ. DESIGN:Meta-analysis of randomized controlled trials. SETTING:Medline, EMBASE, and Cochrane Library searches were performed up to 15 June 2016. PATIENTS:Trials had to enroll adult surgical or critically ill patients for inclusion. INTERVENTIONS:Studies had to compare a liberal versus restrictive threshold for the transfusion of allogeneic packed RBCs. MEASUREMENTS AND MAIN RESULTS:The primary outcome was 30-day all-cause mortality, sub-grouped by surgical and critical care patients. Secondary outcomes included myocardial infarction, stroke, renal failure, allogeneic blood exposure, and length of stay. Odds ratios and weighted mean differences were calculated using random effects meta-analysis. To assess whether subgroups were significantly different, tests for subgroup interaction were used. Subgroup analysis by trials enrolling critically ill versus surgical patients was performed. Twenty-seven randomized controlled trials (10,797 patients) were included. In critical care patients, restrictive transfusion resulted in significantly reduced 30-day mortality compared with liberal transfusion (odds ratio, 0.82; 95% CI, 0.70-0.97). In surgical patients, a restrictive transfusion strategy led to the opposite direction of effect for mortality (odds ratio, 1.31; 95% CI, 0.94-1.82). The subgroup interaction test was significant (p = 0.04), suggesting that the effect of restrictive transfusion on mortality is statistically different for critical care (decreased risk) versus surgical patients (potentially increased risk or no difference). Regarding secondary outcomes, for critically ill patients, a restrictive strategy resulted in reduced risk of stroke/transient ischemic attack, packed RBC exposure, transfusion reactions, and hospital length of stay. In surgical patients, restrictive transfusion resulted in reduced packed RBC exposure. CONCLUSIONS:The safety of restrictive transfusion strategies likely differs for critically ill patients versus perioperative patients. Further trials investigating transfusion strategies in the perioperative setting are necessary.
Project description:The association between red blood cell (RBC) transfusion strategies and health care-associated infection is not fully understood.To evaluate whether RBC transfusion thresholds are associated with the risk of infection and whether risk is independent of leukocyte reduction.MEDLINE, EMBASE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, Cochrane Database of Sytematic Reviews, ClinicalTrials.gov, International Clinical Trials Registry, and the International Standard Randomized Controlled Trial Number register were searched through January 22, 2014.Randomized clinical trials with restrictive vs liberal RBC transfusion strategies.Twenty-one randomized trials with 8735 patients met eligibility criteria, of which 18 trials (n?=?7593 patients) contained sufficient information for meta-analyses. DerSimonian and Laird random-effects models were used to report pooled risk ratios. Absolute risks of infection were calculated using the profile likelihood random-effects method.Incidence of health care-associated infection such as pneumonia, mediastinitis, wound infection, and sepsis.The pooled risk of all serious infections was 11.8% (95% CI, 7.0%-16.7%) in the restrictive group and 16.9% (95% CI, 8.9%-25.4%) in the liberal group. The risk ratio (RR) for the association between transfusion strategies and serious infection was 0.82 (95% CI, 0.72-0.95) with little heterogeneity (I2?=?0%; ?2 <.0001). The number needed to treat (NNT) with restrictive strategies to prevent serious infection was 38 (95% CI, 24-122). The risk of infection remained reduced with a restrictive strategy, even with leukocyte reduction (RR, 0.80 [95% CI, 0.67-0.95]). For trials with a restrictive hemoglobin threshold of <7.0 g/dL, the RR was 0.82 (95% CI, 0.70-0.97) with NNT of 20 (95% CI, 12-133). With stratification by patient type, the RR was 0.70 (95% CI, 0.54-0.91) in patients undergoing orthopedic surgery and 0.51 (95% CI, 0.28-0.95) in patients presenting with sepsis. There were no significant differences in the incidence of infection by RBC threshold for patients with cardiac disease, the critically ill, those with acute upper gastrointestinal bleeding, or for infants with low birth weight.Among hospitalized patients, a restrictive RBC transfusion strategy was associated with a reduced risk of health care-associated infection compared with a liberal transfusion strategy. Implementing restrictive strategies may have the potential to lower the incidence of health care-associated infection.
Project description:Research supports the efficacy and safety of restrictive transfusion protocols to reduce avoidable RBC transfusions, but evidence of their effectiveness in practice is limited. This study assessed whether admission to an ICU with an restrictive transfusion protocol reduces the likelihood of transfusion for adult patients.Observational study using data from the multicenter, cohort Critical Illness Outcomes Study. Patient-level analyses were conducted with RBC transfusion on day of enrollment as the outcome and admission to an ICU with a restrictive transfusion protocol as the exposure of interest. Covariates included demographics, hospital course (e.g., lowest hematocrit, blood loss), severity of illness (e.g., Sequential Organ Failure Assessment score), interventions (e.g., sedation/analgesia), and ICU characteristics (e.g., size). Multivariable logistic regression modeling assessed the independent effects of restrictive transfusion protocols on transfusions.Fifty-nine U.S. ICUs.A total of 6,027 adult ICU patients.None.Of the 59 study ICUs, 24 had an restrictive transfusion protocol; 2,510 patients (41.6%) were in an ICU with an restrictive transfusion protocol. The frequency of RBC transfusion among patients with severe (hematocrit, < 21%), moderate (hematocrit, 21-30%), and mild (hematocrit, > 30%) anemia in restrictive transfusion protocol ICUs was 67%, 19%, and 4%, respectively, compared with 60%, 14%, and 2% for those in ICUs without an restrictive transfusion protocol. Only 27% of transfusions were associated with a hematocrit less than 21%. Adjusting for confounding factors, restrictive transfusion protocols independently reduced the odds of transfusion in moderate anemia with an odds ratio of 0.59 (95% CI, 0.36-0.96) while demonstrating no effect in mild (p = 0.93) or severe (p = 0.52) anemia.In this sample of ICU patients, transfusions often occurred outside evidence-based guidelines, but admission to an ICU with an restrictive transfusion protocol did reduce the risk of transfusion in moderately anemic patients controlling for patient and ICU factors. This study supports the effectiveness of restrictive transfusion protocols for influencing transfusions in clinical practice.
Project description:This study sought to evaluate whether restrictive blood transfusion strategies are associated with a risk of infection in orthopedic patients by conducting a meta-analysis of randomized controlled trials (RCTs). RCTs with restrictive versus liberal red blood cell (RBC) transfusion strategies were identified by searching Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from their inception to December 2014. Eight RCTs with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. The pooled risk ratio [RR] for the association between transfusion strategy and infection was 0.65 (95% CI, 0.47-0.91; p = 0.012), and the number of patients needed to treat to avoid an infection using a restrictive transfusion strategy was 62. No heterogeneity was observed. The sensitivity analysis indicated unstable results, and no significant publication bias was observed. This meta-analysis of RCTs demonstrates that restrictive transfusion strategies in orthopedic patients result in a significant reduction in infections compared with more liberal strategies.
Project description: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.
Project description:OBJECTIVE:Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. BACKGROUND:Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. METHODS:This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8?g/dL) or liberal (hemoglobin 10-11?g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS:Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3?±?32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8?±?44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, ? test). CONCLUSIONS:A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).