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      Impact of restrictive red blood cell transfusion strategy on thrombosis‐related events: A meta‐analysis and systematic review

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          Abstract

          Background and Objectives

          There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta‐analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis‐related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated.

          Materials and Methods

          We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random‐effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data.

          Results

          Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44–0.94; p = 0.020; I 2 = 0.0%, very low‐quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR = 0.83; 95% CI 0.64–1.09; p = 0.180; I 2 = 0.0%, very low‐quality evidence) or myocardial infarction (RR = 1.05; 95% CI 0.87–1.26; p = 0.620; I 2 = 0.0%, low‐quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups).

          Conclusions

          A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.

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          Most cited references61

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          RoB 2: a revised tool for assessing risk of bias in randomised trials

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            Transfusion strategies for acute upper gastrointestinal bleeding.

            The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).
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              Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.

              Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002). Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. clinicaltrials.gov Identifier: NCT01021631.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Vox Sanguinis
                Vox Sanguinis
                Wiley
                0042-9007
                1423-0410
                July 2022
                March 25 2022
                July 2022
                : 117
                : 7
                : 887-899
                Affiliations
                [1 ] School of Management University of Science and Technology of China Hefei Anhui China
                [2 ] Lee Kong Chian School of Business Singapore Management University Singapore
                [3 ] School of Management Technical University of Munich Heilbronn Germany
                [4 ] Munich Data Science Institute Technical University of Munich Munich Germany
                [5 ] Department of Cardiac, Thoracic and Vascular Surgery National University Hospital Singapore
                Article
                10.1111/vox.13274
                54e7f6eb-4f3c-4672-bc52-398cc14f9ffd
                © 2022

                http://creativecommons.org/licenses/by-nc-nd/4.0/

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