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Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders
Malouf R, Ashraf A, Hadjinicolaou A V, Doree C, Hopewell S, Estcourt L J
The Cochrane Database of Systematic Reviews. 2018;5:CD012342.
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Abstract
BACKGROUND Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries. OBJECTIVES To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders. SEARCH METHODS We searched for randomised controlled trials (RCTs), non-RCTs, and controlled before-after studies (CBAs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2017, Issue 9), Ovid MEDLINE (from 1946), Ovid Embase (from 1974), PubMed (e-publications only), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 12 October 2017. SELECTION CRITERIA We included RCTs, non-RCTs, and CBAs that involved the transfusion of platelet concentrates (prepared either from individual units of whole blood or by apheresis any dose, frequency, or transfusion trigger) and given to treat or prevent bleeding among people with congenital or acquired bone marrow failure disorders.We excluded uncontrolled studies, cross-sectional studies, and case-control studies. We excluded cluster-RCTs, non-randomised cluster trials, and CBAs with fewer than two intervention sites and two control sites due to the risk of confounding. We included all people with long-term bone marrow failure disorders that require platelet transfusions, including neonates. We excluded studies of alternatives to platelet transfusion, or studies of people receiving intensive chemotherapy or a stem cell transplant. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures outlined by Cochrane. Due to the absence of evidence we were unable to report on any of the review outcomes. MAIN RESULTS We identified one RCT that met the inclusion criteria for this review. The study enrolled only nine adults with MDS over a three-year study duration period. The trial was terminated due to poor recruitment rate (planned recruitment 60 participants over two years). Assessment of the risk of bias was not possible for all domains. The trial was a single-centre, single-blind trial. The clinical and demographic characteristics of the participants were never disclosed. The trial outcomes relevant to this review were bleeding assessments, mortality, quality of life, and length of hospital stay, but no data were available to report on any of these outcomes.We identified no completed non-RCTs or CBAs.We identified no ongoing RCTs, non-RCTs, or CBAs. AUTHORS' CONCLUSIONS We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.
Clinical Commentary
Xiangrong He, MD, PhD & Claudia S. Cohn, MD, PhD, both of University of Minnesota, Department of Laboratory Medicine and Pathology.
What is known?
Thrombocytopenia represents a common problem for patients withchronic bone marrow failure disorders, the most common of which are myelodysplastic syndrome (MDS) and anaplastic anemia (AA). In addition to thrombocytopenia, both morphologic and functional platelet abnormalities may be seen in these patients as well. Platelet transfusion support is the primary management option for thrombocytopenia and active bleeding in these patients. Platelets are usually transfused prophylactically at counts less than 10 x 109/L and with higher counts in patients with hemorrhage. As compared with no prophylaxis, prophylactic platelet transfusions have been shown to be superior in reducing moderate to severe bleeding, primarily in people with leukemia. However, the evidence of prophylactic use for platelet transfusions in people with chronic bone marrow failure is lacking. Meanwhile, platelets are a precious resource and platelet transfusion carries many risks. Thus, avoiding unnecessary prophylactic platelet transfusions will have significant financial and safety implications for health services.
What did this paper set out to examine?
The authors set out to to review in thrombocytopenic patients with chronic bone marrow failure, whether prophylactic transfusions are really necessary or whether these patients can be effectively supported with only therapeutic platelet transfusions given with the onset of bleeding. In particular, they wanted to show that a therapeutic-only platelet transfusion strategy is as effective and safe as a prophylactic platelet transfusion strategy for the prevention of clinically significant bleeding in thrombocytopenic patients with primary bone marrow failure disorders.
What did they show?
The review included all patients with MDS, acquired AA, or congenital bone marrow failure disorders that were not being actively treated with a stem cell transplant or intensive chemotherapy. To maximize the number of studies eligible for inclusion, not only randomized controlled trials (RCTs), but good quality non-RCTs, and controlled before-after studies were included. Only one trial met the inclusion criteria for this review. Unfortunately, the trial was incomplete due to an unexpected slow recruiting rate. Therefore, no results were provided by the trial authors. Although the review was unable to make any recommendations on prophylactic platelet transfusion policies for this patient population, it did identify an urgent need for good quality studies in this area.
What are the implications for practice and for future work?
Thrombocytopenia (platelet counts < 10 x 109/L) is one of the most common complications in patients with chronic bone marrow failure. For example, 40% to 65% of MDS patients have thrombocytopenia. Meanwhile, in some Western countries, bone marrow failure is one of the most common underlying reasons for receiving a prophylactic platelet transfusion. However, guidelines on a therapeutic platelet transfusion strategy versus a prophylactic platelet transfusion strategy in this population are still lacking. Due to the absence of relevant data, the current review was not able to reach any conclusions on the safety and efficacy of prophylactic platelet transfusion compared with therapeutic platelet transfusion for patients with chronic bone marrow failure. Nontheless, this review identified a major gap in the literature and underscored the urgency of prioritizing research in this area. In the meantime, platelet transfusions for people with bone marrow disorders should still be managed according to national transfusion guidelines.
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Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia
Estcourt LJ, Ingram C, Doree C, Trivella M, Stanworth SJ
The Cochrane Database of Systematic Reviews. 2016;((5)):CD011980.
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BACKGROUND People with a low platelet count (thrombocytopenia) often require lumbar punctures or an epidural anaesthetic. Lumbar punctures can be diagnostic (haematological malignancies, epidural haematoma, meningitis) or therapeutic (spinal anaesthetic, administration of chemotherapy). Epidural catheters are placed for administration of epidural anaesthetic. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to lumbar punctures and epidural anaesthesia, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to these procedures varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding appears to be low but if bleeding occurs it can be very serious (spinal haematoma). Therefore, people may be exposed to the risks of a platelet transfusion without any obvious clinical benefit. OBJECTIVES To assess the effects of different platelet transfusion thresholds prior to a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count). SEARCH METHODS We searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 3 March 2016. SELECTION CRITERIA We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people of any age with thrombocytopenia requiring insertion of a lumbar puncture needle or epidural catheter. We only included RCTs published in English. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We identified no completed or ongoing RCTs in English. We did not exclude any completed or ongoing RCTs because they were published in another language. AUTHORS' CONCLUSIONS There is no evidence from RCTs to determine what is the correct platelet transfusion threshold prior to insertion of a lumbar puncture needle or epidural catheter. There are no ongoing registered RCTs assessing the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia. Any future RCT would need to be very large to detect a difference in the risk of bleeding. We would need to design a study with at least 47,030 participants to be able to detect an increase in the number of people who had major procedure-related bleeding from 1 in 1000 to 2 in 1000.
Clinical Commentary
Richard Kaufman MD, Brigham and Women’s Hospital, Boston
What is known?
In rare cases, bleeding complicates lumbar punctures and epidural anesthesia. The clinical consequences of bleeding in this setting range from trivial (traumatic tap detectable by cerebrospinal fluid cell count only) to devastating (spinal hematoma/paralysis). Most cases of spinal hematoma following lumbar puncture have been reported in patients with platelet counts below 50 X 109 cells/Lalthough other risk factors for bleeding were present in nearly all of these cases.1 Platelet transfusions are often administered prophylactically to thrombocytopenic patients having a lumbar puncture or epidural anesthesia. But what constitutes a safe minimum platelet count to perform these procedures is unclear, and clinical practices and published practice guidelines vary widely. This is an important topic because: (1) lumbar punctures and epidural anesthesia are performed commonly; (2) these procedures have rare but serious risks; (3) platelet transfusions carry a range of infectious and noninfectious risks; and (4) platelet units are expensive and limited in availability.
What did this paper set out to examine?
The authors conducted a systematic review of the literature aimed at evaluating the risks and benefits of different platelet transfusion thresholds before a lumbar puncture or epidural anesthesia in thrombocytopenic patients. This was an update of a 2016 Cochrane Review.
What did they show?
The authors found that the published literature on this topic remains extremely limited. They identified no high-quality studies. After rigorously screening 999 published reports, the authors included in their analysis only three retrospective cohort studies describing participants who received or did not receive lumbar puncture. One study was in adults; the other two were in children. No study compared different platelet count thresholds before a procedure. No major bleeding complications occurred in the two studies reporting this outcome (150 participants). There was no difference in minor bleeding (traumatic taps) among pediatric or adult patients who received or did not receive platelet transfusion pre-procedure. The authors concluded that no clinical study evidence exists on which to base a correct platelet transfusion threshold before lumbar puncture or epidural anesthesia.
At this time, it is impossible to make firm recommendations on whether platelet transfusions should be administered before lumbar puncture or epidural anesthesia in thrombocytopenic children or adults. A safe minimum platelet count for performing these procedures cannot be identified based on the existing data. Until stronger data allow us to better understand the risks and benefits of platelet transfusion before lumbar puncture or epidural anesthesia, practices will vary among clinicians and will remain a matter of clinical judgment.
What are the implications for practice and for future work?
What are the implications for future research?Because bleeding complication rates are so low in the setting of lumbar puncture and epidural anesthesia, the authors estimate that performing a randomized trial would require more than 47,000 participants. Utilizing large electronic patient registries/databases thus appears to be the only realistic way that our understanding in this area could be improved moving forward.
Predicting bleeding in the setting of any invasive procedure has proven to be remarkably difficult. Hemostasis is complex; bleeding from most procedures is rare; and the tools that we have to assess bleeding risk are crude. Platelet counts tell us nothing about platelet hemostatic function. Other variables, including medications, coagulation factor activity, tissue integrity, and disease state may predominate in determining a patient’s bleeding risk. Platelet counts are easy to measure, but hopefully in the future we will discover better ways to determine whether a platelet transfusion should be given.
What are the implications for future practice? At this time, it is impossible to make firm recommendations on whether platelet transfusions should be administered before lumbar puncture or epidural anesthesia in thrombocytopenic children or adults. A safe minimum platelet count for performing these procedures cannot be identified based on the existing data. Until stronger data allow us to better understand the risks and benefits of platelet transfusion before lumbar puncture or epidural anesthesia, practices will vary among clinicians and will remain a matter of clinical judgment.
References
1. Van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol. 148(1):15-25.
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Blood transfusion after percutaneous coronary intervention and risk of subsequent adverse outcomes: a systematic review and meta-analysis
Kwok CS, Sherwood MW, Watson SM, Nasir SB, Sperrin M, NolanJ, Kinnaird T, Kiatchoosakun S, Ludman PF, de Belder MA, et al
JACC: Cardiovascular Interventions. 2015;8((3):):436-46.
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OBJECTIVES This study sought to define the prevalence and prognostic impact of blood transfusions in contemporary percutaneous coronary intervention (PCI) practice. BACKGROUND Although the presence of anemia is associated with adverse outcomes in patients undergoing PCI, the optimal use of blood products in patients undergoing PCI remains controversial. METHODS A search of EMBASE and MEDLINE was conducted to identify PCI studies that evaluated blood transfusions and their association with major adverse cardiac events (MACE) and mortality. Two independent reviewers screened the studies for inclusion, and data were extracted from relevant studies. Random effects meta-analysis was used to estimate the risk of adverse outcomes with blood transfusions. Statistical heterogeneity was assessed by considering the I(2) statistic. RESULTS Nineteen studies that included 2,258,711 patients with more than 54,000 transfusion events were identified (prevalence of blood transfusion 2.3%). Crude mortality rate was 6,435 of 50,979 (12.6%, 8 studies) in patients who received a blood transfusion and 27,061 of 2,266,111 (1.2%, 8 studies) in the remaining patients. Crude MACE rates were 17.4% (8,439 of 48,518) in patients who had a blood transfusion and 3.1% (68,062 of 2,212,730) in the remaining cohort. Meta-analysis demonstrated that blood transfusion was independently associated with an increase in mortality (odds ratio: 3.02, 95% confidence interval: 2.16 to 4.21, I(2) = 91%) and MACE (odds ratio: 3.15, 95% confidence interval: 2.59 to 3.82, I(2) = 81%). Similar observations were recorded in studies that adjusted for baseline hematocrit, anemia, and bleeding. CONCLUSIONS Blood transfusion is independently associated with increased risk of mortality and MACE events. Clinicians should minimize the risk for periprocedural transfusion by using available bleeding-avoidance strategies and avoiding liberal transfusion practices.Copyright 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Clinical Commentary
What is known?
Allogenic red cell transfusion is associated with adverse clinical outcomes in many clinical settings.
What did this paper set out to examine?
The authors conducted a systematic review of the evidence that relates to the relationship between red cell transfusion and adverse clinical outcomes in patients undergoing percutaneous coronary interventions (PCI). The study is timely because the increasingly elderly population referred for PCI are at increased risk of anaemia and acute haemorrhage, the two key indications for red cell transfusion.
What did they show?
The authors conducted a robust and well described systematic review of relevant databases. They identified 19 observational analyses that included 2,258,711 patients met their eligibility criteria; reporting of transfusions, death and Major Adverse Cardiac Events (MACE). The included studies were of mixed quality and showed differences in their design, definitions of primary and secondary exposures, duration of follow up, and type of analyses. Pooled effect estimates demonstrated strong associations between transfusion, mortality and MACE, although these analyses also demonstrated significant heterogeneity. Sub group analyses that included only studies with longer follow-up, or that contained adjustment for confounders such as transfusion volume or anaemia showed consistent associations between transfusion and harm, with some reduction in heterogeneity.
What are the implications for practice and for future work?
Implications for future research: The authors conclude that their data cannot demonstrate a causal relationship between transfusion and adverse outcomes in these patients. However they do discuss the possible pathological effects of transfusion and conclude that their data should support more restrictive transfusion practice. Implications for future practice: This study generates the hypothesis that reduced exposure to red cells may have benefits in these high risk patients. This hypothesis should be tested in a randomised controlled clinical trial. It is premature to suggest that the evidence presented here makes a case for restrictive practice.
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Risks associated with red blood cell transfusion in the trauma population, a meta-analysis
Patel SV, Kidane B, Klingel M, Parry N
Injury. 2014;45((10):):1522-33.
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INTRODUCTION A previous meta-analysis has found an association between red blood cell (RBC) transfusions and mortality in critically ill patients, but no review has focused on the trauma population only. OBJECTIVES To determine the association between RBC transfusion and mortality in the trauma population, with secondary outcomes of multiorgan failure (MOF) and acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). DATA SOURCES EMBASE (1947-2012) and MEDLINE (1946-2012). STUDY ELIGIBILITY CRITERIA Randomized controlled trials and observational studies were to be included if they assessed the association between RBC transfusion and either the primary (mortality) or secondary outcomes (MOF, ARDS/ALI). PARTICIPANTS Trauma patients. EXPOSURE Red blood cell transfusion. METHODS A literature search was completed and reviewed in duplicate to identify eligible studies. Studies were included in the pooled analyses if an attempt was made to determine the association between RBC and the outcomes, after adjusting for important confounders. A random effects model was used for and heterogeneity was quantified using the I(2) statistic. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS 40 observational studies were included in the qualitative review. Including studies which adjusted for important confounders found the odds of mortality increased with each additional unit of RBC transfused (9 Studies, OR 1.07, 95%CI 1.04-1.10, I(2) 82.9%). The odds of MOF (3 studies, OR 1.08, 95%CI 1.02-1.14, I(2) 95.9%) and ARDS/ALI (2 studies, OR 1.06, 95%CI 1.03-1.10, I(2) 0%) also increased with each additional RBC unit transfused. CONCLUSIONS We have found an association between RBC transfusion and the primary and secondary outcomes, based on observational studies only. This represents the extent of the published literature. Further interventional studies are needed to clarify how limiting transfusion can affect mortality and other outcomes. Copyright 2014 Elsevier Ltd. All rights reserved.
Clinical Commentary
Dr Annemarie Docherty, University of Edinburgh, Edinburgh, UK.
What is known?
Death from haemorrhage is the second most common cause of death in the trauma population and a high proportion of severely injured patients receive red blood cell transfusions. Evidence from randomised controlled trials in critically ill patients support a restrictive transfusion threshold, however the effect of transfusion on outcomes in trauma may differ due to the timing and amount of transfusion required. Trauma patients may be unstable or actively bleeding, as opposed to the slow decline in haemoglobin often seen in critical care. Evidence in the trauma population is based primarily on small observational studies.
What did this paper set out to examine?
This systematic review and meta-analysis set out to assess the association between red blood cell transfusion and mortality in the trauma population. Secondary outcomes included acute respiratory distress syndrome or acute lung injury (ARDS/ALI) and multiorgan failure. Comparative observational and interventional studies were eligible for inclusion.
What did they show?
The authors included 40 studies in the qualitative review. No randomised controlled trials addressed the study question. All studies were observational cohort studies, which increased the risk of selection bias and confounding. Particularly relevant confounders were injury severity and other measures of shock which were strongly associated with the study outcomes. The authors assessed the quality of the studies using the Newcastle-Ottawa Scale, and the quality of the meta-analysis using the GRADE guidelines.
There was significant heterogeneity. Study size varied from 29 to 25,299. Timing of red blood cell transfusion varied considerably from studies that included transfusion within 24-48 hours only, total in-hospital transfusion, to studies that excluded patients transfused within 48 hours of admission. There were also marked differences in the categorisation of red blood cell transfusion: continuous variable (per unit change), binary variable (transfused/not transfused) and a categorical variable. In addition to this, patient populations also varied: multiply injured patients, patients with only one system injured, massively transfused patients, patients only admitted to the intensive care unit, surgical patients only, intubated patients only, and various injury severity score cutoffs.
Seventeen studies attempted to determine the effect of transfusion on mortality after adjusting for important confounders, and nine of these had enough information to be pooled in the meta-analysis. Eight studies found that red blood cell transfusion was associated with increased odds of mortality, and the adjusted pooled analysis showed an increase in the odds of mortality with each additional unit transfused (OR 1.07, 95%CI 1.04-1.10, p<0.001, I^2=94.6%). The authors graded this evidence as low.
Six studies attempted to determine the adjusted association with multiorgan failure. The odds of multiorgan failure increased with each additional unit of blood (OR 1.08, 95%CI 1.02-1.14, p=0.012, I^2=95.9%). The grade of evidence was moderate.
Six studies assessed the adjusted association between transfusion and ARDS, but only two had enough information to be included in the meta-analysis (transfused vs not transfused: OR 2.04, 95%CI 1.47-2.83, p<0.001, I^2=0%). The authors graded this evidence as very low.
What are the implications for practice and for future work?
The observational studies all showed an association between transfusion and mortality and other negative outcomes. However, there was considerable heterogeneity between the studies, and as the authors acknowledge, it is likely that significant confounding persisted even after attempts to adjust for injury and illness severity. The authors have graded the evidence as very low to moderate, and it is not possible to refine red blood cell transfusion practice in trauma on the basis of these observational studies.
This systematic review highlights the lack of evidence for red blood cell transfusion in trauma, and the need for a robust randomised controlled trial in this population. This would minimise confounding and bias, and give a definitive answer regarding the effect of red blood cell transfusion on mortality.
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Association of red blood cell transfusion and in-hospital mortality in patients admitted to the intensive care unit: a systematic review and meta-analysis
Zheng Y, Lu C, Wei S, Li Y, Long L, Yin P
Critical Care (London, England). 2014;18((6):):515.
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INTRODUCTION Previous research has debated whether red blood cell (RBC) transfusion is associated with decreased or increased mortality in patients admitted to the intensive care unit (ICU). We conducted a systematic review and meta-analysis to assess the relationship of RBC transfusion with in-hospital mortality in ICU patients. METHODS We carried out a literature search on Medline (1950 through May 2013), Web of Science (1986 through May 2013) and Embase (1980 through May 2013). We included all prospective and retrospective studies on the association between RBC transfusion and in-hospital mortality in ICU patients. The relative risk for the overall pooled effects was estimated by random effects model. Sensitivity analyses were conducted to assess potential bias. RESULTS The meta-analysis included 28,797 participants from 18 studies. The pooled relative risk for transfused versus nontransfused ICU patients was 1.431 (95% CI, 1.105 to 1.854). In sensitivity analyses, the pooled relative risk was 1.211 (95% CI, 0.975 to 1.505) if excluding studies without adjustment for confounders, 1.178 (95% CI, 0.937 to 1.481) if excluding studies with relative high risk of bias, and 0.901 (95% CI, 0.622 to 1.305) if excluding studies without reporting hazard ratio (HR) or relative risk (RR) as an effect size measure. Subgroup analyses revealed increased risks in studies enrolling patients from all ICU admissions (RR 1.513, 95%CI 1.123 to 2.039), studies without reporting information on leukoreduction (RR 1.851, 95%CI 1.229 to 2.786), studies reporting unadjusted effect estimates (RR 3.933, 95%CI 2.107 to 7.343), and studies using odds ratio as an effect measure (RR 1.465, 95%CI 1.049 to 2.045). Meta-regression analyses showed that RBC transfusion could decrease risk of mortality in older patients (slope coefficient -0.0417, 95%CI -0.0680 to -0.0154). CONCLUSIONS There is lack of strong evidence to support the notion that ICU patients who receive RBC transfusion have an increased risk of in-hospital death. In studies adjusted for confounders, we found that RBC transfusion does not increase the risk of in-hospital mortality in ICU patients. Type of patient, information on leukoreduction, statistical method, mean age of patient enrolled and publication year of the article may account for the disagreement between previous studies.
Clinical Commentary
Dr Annemarie Docherty, University of Edinburgh, Edinburgh, UK.
What is known?
Anaemia is prevalent in critically ill patients, and is associated with poor outcomes including acute myocardial infarction, heart failure, chronic kidney disease and risk of death. In critically ill patients, the standard method of reversing anaemia is with transfusion of red blood cells, with the aim of improving oxygen delivery to the tissues. However, blood transfusion is not without risks. These include immunosuppression, risk for infection, transfusion reactions and transfusion-related acute lung injury. There is conflicting evidence surrounding the association between red blood cell transfusion and mortality, with some studies suggesting a higher risk of death in transfused patients, and others finding a lower risk of death.
What did this paper set out to examine?
The authors have set out to examine whether there is an association between red blood cell transfusion and mortality in critically ill patients. The authors have performed a meta-analysis of all published retrospective and prospective observational studies comparing red blood cell transfused with non-transfused ICU patients, looking at all-cause in-hospital mortality, and risk factors of death in transfused patients.
What did they show?
The authors identified 18 observational studies which looked at mortality of transfused patients. Eight studies were prospective, and the other ten retrospective, six studies were very high overall quality, nine studies high overall quality and three studies median overall quality. The overall pooled risk ratio of in-hospital mortality of transfused patients compared to non-transfused patients was 1.431 (95%CI 1.105 to 1.854). However, in order to account for the impact of the observational design of the studies on the results, they performed several sensitivity analyses, including only studies that adjusted for confounders, only high quality studies, and only studies that included risk or hazard ratios. When only including studies that adjusted for confounding (of particular importance in observational studies), the RR was 1.211 (95%CI 0.795 to 1.505). The authors performed a subgroup analysis looking at different types of admission (sepsis and shock, surgical, trauma, and other). There was no association between RBC transfusion and mortality in each type of admission, however the pooled effect estimate suggested that type of admission was a significant predictor of in-hospital mortality. Other significant predictors were age of patient, and year of publication. Recent studies were more likely to report lower risk ratios, which the authors suggest means that blood transfusion may have got safer over time.
What are the implications for practice and for future work?
As a result of these observational limitations, although this systematic review suggests that RBC transfusion is not linked to in-hospital mortality, a randomised controlled trial designed and powered to answer this question would be required to determine causality. This review suggests that in the heterogenous ICU population, there is no association between RBC transfusion and in-hospital mortality after adjustment for confounders. Clinicians can perhaps be reassured that there does not appear to be an inherent risk with RBC transfusion, and that the decision to transfuse should be based on assessment of the patient’s physiological status and comorbidity.