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Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: an overview of systematic reviews
Trentino KM, Farmer SL, Leahy MF, Sanfilippo FM, Isbister JP, Mayberry R, Hofmann A, Shander A, French C, Murray K
BMC Med. 2020;18(1):154
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Abstract
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.
PICO Summary
Population
Patients assigned to red cell transfusion strategies based on haemoglobin thresholds (19 studies).
Intervention
Restrictive transfusion strategy.
Comparison
Liberal transfusion strategy.
Outcome
Of the meta-analyses presenting high- to moderate-quality evidence, 12 reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and 4 reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. 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, and transfusion dosing regimens.
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Red blood cell transfusion: a clinical practice guideline from the AABB
Carson JL, Grossman BJ, Kleinman S, Tinmouth AT, Marques MB, Fung MK, Holcomb JB, Illoh O, Kaplan LJ, Katz LM, et al
Annals of Internal Medicine. 2012;157((1):):49-58.
Abstract
Description: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children. Methods: These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence). 2012 American College of Physicians.
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Evidence-based practice guidelines for plasma transfusion
Roback JD, Caldwell S, Carson J, Davenport R, Drew MJ, Eder A, Fung M, Hamilton M, Hess JR, Luban N, et al
Transfusion. 2010;50((6):):1227-1239.
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Abstract
BACKGROUND There is little systematically derived evidence-based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma. STUDY DESIGN AND METHODS A systematic review (SR) and meta-analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence-based plasma transfusion guidelines as well as identify areas for future investigation. RESULTS Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients. CONCLUSION We have systematically developed evidence-based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion.