Background: There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality. Methods: This was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels. Results: We included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens. Conclusions: Meta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy. Trial registration: PROSPERO CRD42019120503

As defined by evidence-based medicine randomized controlled trials rank higher than observational studies in the hierarchy of clinical research. Accordingly, when assessing the effects of treatments on patient outcomes, there is a tendency to focus on the study method rather than also appraising the key elements of study design. A long-standing debate regarding findings of randomized controlled trials compared with those of observational studies, their strengths and limitations and questions regarding causal inference, has recently come into focus in relation to research assessing patient outcomes in transfusion medicine. Observational studies are seen to have limitations that are largely avoided with randomized controlled trials, leading to the view that observational studies should not generally be used to inform practice. For example, observational studies examining patient outcomes associated with blood transfusion often present higher estimates of adverse outcomes than randomized controlled trials. Some have explained this difference as being a result of observational studies not properly adjusting for differences between patients transfused and those not transfused. However, one factor often overlooked, likely contributing to these variances between study methods is different exposure criteria. Another common to both study methods is exposure dose, specifically, measuring units transfused during only a part of the patient’s hospital stay. When comparing the results of observational studies with randomized controlled trials assessing transfusion outcomes it is important that one consider not only the study method, but also the key elements of study design. Any study, regardless of its method, should focus on accurate measurement of the exposure and outcome variables of interest. Failure to do so may subject the study, regardless of its type, to bias and the need to interpret the results with caution.

Background and Objectives: To explore variation in red blood cell transfusion rates between hospitals, and the extent to which this can be explained. A secondary objective was to assess whether hospital transfusion rates are associated with maternal morbidity.Materials and Methods: Linked hospital discharge and birth data were used to identify births (n = 279 145) in hospitals with at least 10 deliveries per annum between 2008 and 2010 in New South Wales, Australia. To investigate transfusion rates, a series of random‐effects multilevel logistic regression models were fitted, progressively adjusting for maternal, obstetric and hospital factors. Correlations between hospital transfusion and maternal, neonatal morbidity and readmission rates were assessed.Results: Overall, the transfusion rate was 1·4% (hospital range 0·6–2·9) across 89 hospitals. Adjusting for maternal casemix reduced the variation between hospitals by 26%. Adjustment for obstetric interventions further reduced variation by 8% and a further 39% after adjustment for hospital type (range 1·1–2·0%). At a hospital level, high transfusion rates were moderately correlated with maternal morbidity (0·59, P = 0·01), but not with low Apgar scores (0·39, P = 0·08), or readmission rates (0·18, P = 0·29).Conclusion: Both casemix and practice differences contributed to the variation in transfusion rates between hospitals. The relationship between outcomes and transfusion rates was variable; however, low transfusion rates were not associated with worse outcomes.