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In patients with myocardial infarction and anemia, a liberal transfusion strategy led to fewer deaths and heart attacks than a restricted transfusion strategy, but the difference was of borderline significance.

In a pragmatic trial, more than 30,000 patients requiring blood transfusion were randomly assigned to receive blood after short-term storage or long-term storage. In-hospital mortality did not differ significantly between the two groups. Red-cell transfusion is one of the most common medical interventions. 1 Blood is stored for up to 42 days before transfusion. Biochemical, structural, and functional changes during storage may reduce oxygen delivery to tissues, and the release of extracellular vesicles and cell-free DNA during storage may cause a hypercoagulable state. 2 Observational studies have suggested that prolonged blood storage is associated with an increased risk of cardiovascular events. 3 Randomized, controlled trials have not shown harm in transfusing red-cell units with a longer duration versus a shorter duration of storage. However, most of these trials have been restricted to high-risk populations and have . . .

In this study, patients were randomly assigned to a transfusion threshold of 9 or 7.5 g per deciliter after cardiac surgery. There was no significant between-group difference in infectious or ischemic events, but more deaths were associated with the lower threshold. Perioperative anemia is common after cardiac surgery and is associated with significant increases in morbidity and mortality. 1 – 3 The transfusion of allogeneic red cells is the preferred treatment for acute anemia and is also used in patients undergoing cardiac surgery; typically, more than 50% of patients receive a perioperative transfusion, 4 , 5 which uses a substantial proportion of blood supplies. 6 Observational studies suggest that transfusion is harmful after cardiac surgery; associations have been reported between transfusion and infection, low cardiac output, acute kidney injury, and death. 2 , 7 , 8 In contrast, randomized, controlled trials of red-cell transfusion with restrictive thresholds (i.e., transfusions . . .

For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4–16 years and had abnormal TCD flow velocities (≥200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140–146) in children who received standard transfusions and 138 cm/s (135–142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10–8·98). Non-inferiority (p=8·82 × 10−16) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. National Heart, Lung, and Blood Institute, National Institutes of Health.

Background The optimal hemoglobin (Hb) threshold to trigger red blood cell transfusions (RBCT) in subarachnoid hemorrhage (SAH) patients is unclear. This study evaluated the impact of liberal versus restrictive transfusion strategies on neurological outcome in patients with SAH. Methods This is a pre-planned secondary analysis of the “TRansfusion Strategies in Acute brain INjured Patients” (TRAIN) study. We included all SAH patients from the original study that were randomized to receive RBCT when Hb levels dropped below 9 g/dL (liberal group) or 7 g/dL (restrictive group). The primary outcome was an unfavorable neurological outcome at 180 days, defined by a Glasgow Outcome Scale Extended score of 1–5. Results Of the 190 SAH patients in the trial, 188 (98.9%) had data available for the primary outcome, with 86 (45.3%) in the liberal group and 102 (53.6%) in the restrictive group. Patients in the liberal group were older than in the restrictive group, but otherwise had similar baseline characteristics. Patients in the liberal group received more RBCT and showed higher Hb levels over time. At 180 days, 57 (66.3%) patients in the liberal group and 78 (76.4%) in the restrictive group had unfavorable outcomes (risk ratio, RR 0.87; 95% confidence intervals, 95% CI 0.71–1.04). Patients in the liberal group had a significantly lower risk of cerebral ischemia (RR 0.63; 95% CI 0.41–0.97). In a multivariate analysis, randomization to the liberal group was associated with a lower risk of unfavorable outcome (RR 0.83, 95% CI 0.70–0.99). Conclusions A liberal transfusion strategy was not associated with a lower incidence of unfavorable outcome after SAH when compared to a restrictive strategy. However, in a multivariable analysis adjusted for confounders randomization to the liberal group was associated with lower risk of unfavorable outcome. The occurrence of cerebral ischemia was significantly lower in the liberal transfusion strategy group. Trial registration ClinicalTrials.gov number—NCT02968654 registered on November 16th, 2016.

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.

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.

Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients. Patients with acute coronary syndrome may benefit from higher hemoglobin levels. We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin <10 g/dL. Patients in the liberal transfusion strategy received one or more units of blood to raise the hemoglobin level ≥10 g/dL. Patients in the restrictive transfusion strategy were permitted to receive blood for symptoms from anemia or for a hemoglobin <8 g/dL. The predefined primary outcome was the composite of death, myocardial infarction, or unscheduled revascularization 30 days post randomization. Baseline characteristics were similar between groups except age (liberal, 67.3; restrictive, 74.3). The mean number of units transfused was 1.6 in the liberal group and 0.6 in the restrictive group. The primary outcome occurred in 6 patients (10.9%) in the liberal group and 14 (25.5%) in the restrictive group (risk difference = 15.0%; 95% confidence interval of difference 0.7% to 29.3%; P = .054 and adjusted for age P = .076). Death at 30 days was less frequent in liberal group (n = 1, 1.8%) compared to restrictive group (n = 7, 13.0%; P = .032). The liberal transfusion strategy was associated with a trend for fewer major cardiac events and deaths than a more restrictive strategy. These results support the feasibility of and the need for a definitive trial.

Hemorrhage coupled with coagulopathy remains the leading cause of preventable in-hospital deaths among trauma patients. Use of a transfusion protocol with a predefined ratio of 1:1:1 (1 each of red blood cells [RBC], frozen plasma [FP] and platelets) has been associated with improved survival in retrospective studies in military and civilian settings, but such a protocol has its challenges and may increase the risk of respiratory complications. We conducted a randomized controlled trial to assess the feasibility of a 1:1:1 transfusion protocol and its effect on mortality and complications among patients with severe trauma. We included 78 patients seen in a tertiary trauma centre between July 2009 and October 2011 who had hypotension and bleeding and were expected to need massive transfusion (≥ 10 RBC units in 24 h). We randomly assigned them to either the fixed-ratio (1:1:1) transfusion protocol (n = 40) or to a laboratory-results–guided transfusion protocol (control; n = 38). The primary outcome, feasibility, was assessed in terms of blood product ratios and plasma wastage. Safety was measured based on 28-day mortality and survival free of acute respiratory distress syndrome. Overall, a transfusion ratio of 1:1:1 was achieved in 57% (21/37) of patients in the fixed-ratio group, as compared with 6% (2/32) in the control group. A ratio of 1:1 (RBC:FP) was achieved in 73% (27/37) in the fixed-ratio group and 22% (7/32) in the control group. Plasma wastage was higher with the intervention protocol (22% [86/390] of FP units v. 10% [30/289] in the control group). The 28-day mortality and number of days free of acute respiratory distress syndrome were statistically similar between the groups. The fixed-ratio transfusion protocol was feasible in our study, but it was associated with increased plasma wastage. Larger randomized trials are needed to evaluate the efficacy of such a protocol in trauma care.

ObjectivesTo compare the effect of liberal versus restrictive transfusion strategies on the proportion of time (%time) spent with intermittent hypoxaemia (IH, ie, arterial haemoglobin oxygen saturation measured by pulse oximetry (SpO2) <80% lasting ≥60 s) in the ‘Effects of Transfusion Thresholds on Neurocognitive Outcome’ (ETTNO) population, and to investigate whether infants with above-median exposure to IH might benefit more from liberal transfusion strategies than those with lower exposure.Design, setting, patientsSecondary analysis in all 554/1013 infants of <1000 g birth weight recruited into the ETTNO trial (mean gestational age 26.2 weeks) with >80% completeness of SpO2 recordings during postnatal days 8–49.InterventionRandomly assigned liberal (n=268) or restrictive (n=286) transfusion strategies, defining transfusion triggers based on postnatal age and health status.Main outcome measures%time with IH, rate and mean duration of IH episodes during postnatal days 8–49. Interaction between exposure to IH and transfusion strategies with respect to ETTNO’s composite primary outcome, death or disability at 24 months corrected age.ResultsThe median (quartile 1–quartile 3) %time with IH was similar between treatment groups (0.91% (0.13%–2.83%) with liberal vs 0.79% (0.16%–2.44%) with restrictive transfusions). There was no interaction between exposure to IH and transfusion strategies on outcome at 24 months.ConclusionsIn infants <1000 g birth weight, a liberal transfusion strategy did not reduce IH. Blood transfusions should not be administered ‘liberally’ to reduce IH or to improve neurocognitive outcome in infants with above-average exposure to IH.Trial registration number NCT01393496.