Systematic reviews of guidelines and studies for single versus multiple unit transfusion strategies
BACKGROUND Recent recommendations indicate that one red blood cell (RBC) unit should be transfused at a time, with reassessment after each transfusion, which may be extrapolated from literature supporting restrictive transfusion triggers rather than specific evidence. Therefore, two systematic reviews were performed to identify the following: 1) RBC transfusion guidelines and review articles to determine if single- or multiple-unit transfusion strategies are recommended and 2) studies comparing strategies for evidence of benefit. STUDY DESIGN AND METHODS MEDLINE, EMBASE, CINAHL, Web of Science, National Guideline Clearinghouse, and Trip Database were searched (inception to June 2017). For the first review, the proportion of articles with single/multiple-unit recommendations was assessed and stratified by article type. For the second review, the primary outcome was RBC use. Secondary outcomes included proportion of transfusion episodes using a single-unit strategy, length of stay, and mortality. RESULTS The first review identified 145 articles for analysis, with 51 transfusion guidelines. Only 14 guidelines (27%) made a recommendation, with most (93%) recommending single-unit transfusions. The second review identified seven cohort studies comparing preimplementation and postimplementation of a policy encouraging single-unit transfusion strategies. Meta-analysis could not be performed for outcomes given inconsistencies in reporting. RBC use decreased by approximately 10 to 41% across studies. CONCLUSION Transfusion guidelines lack recommendations to transfuse to a single-unit strategy. Mostly retrospective cohort studies (six of seven) are inconsistent in outcome reporting but suggest improved RBC use. Further high-quality studies could identify the benefits of a single-unit transfusion strategy, determine the applicability to different clinical settings, and inform future practice guidelines.
Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial
The Lancet. Haematology. 2017;4((11):):e544-e552. e544
BACKGROUND No randomised trials have addressed whether exposure to red blood cells (RBCs) stored longer than 35 days is associated with harm in patients. We aimed to assess the risk of in-hospital mortality associated with transfusing blood stored longer than 35 days. METHODS We did a secondary analysis of the INforming Fresh versus Old Red cell Management (INFORM) trial, a pragmatic, multicentre, randomised controlled trial of patients (≥18 years) admitted to one of six hospitals in Australia, Canada, Israel, and the USA and expected to need RBC transfusions. Patients were randomly assigned (2:1) to receive blood in inventory stored for the longest time (standard care) or the shortest time, using a random allocation schedule and stratified by centre and patient ABO blood group. The primary objective of the INFORM trial was to assess all-cause in-hospital mortality in patients with blood group A and O who were transfused. For our exploratory secondary analysis, we classified individuals into one of three mutually exclusive exposure categories on the basis of the maximum storage duration of any blood unit patients had received on each day in hospital: exclusively exposed to RBCs stored no longer than 7 days, exposed to at least one unit of RBCs stored 8-35 days, and exposed to least one unit of RBCs stored longer than 35 days. Our primary objective was to determine the effect on risk of in-hospital death of time-dependent exposure to RBCs stored longer than 35 days compared with exclusive exposure to RBCs stored no longer than 7 days, both in patients of blood groups A and O and all patients. The INFORM trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN08118744. FINDINGS Between April 2, 2012, and Oct 21, 2015, 31 497 patients were recruited, and 24 736 patients were eligible for inclusion in this analysis. We excluded nine patients for whom information about the storage duration of transfused blood was missing and one patient whose sex was unknown. 4480 (18%) patients were exposed to RBCs with longest storage, 1392 (6%) patients were exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were exposed to RBCs stored 8-35 days. Median follow-up was 11 days (IQR 6-20). Exposure to RBCs stored longer than 35 days was not associated with increased risk of in-hospital death compared with exclusive exposure to the freshest RBC units after adjusting for demographic variables, diagnosis category, and blood product use history (in patients with blood group A or O: hazard ratio 0.94, 95% CI 0.73-1.20, p=0.60; in all patients: 0.91, 0.72-1.14, p=0.40). The risk of in-hospital death also did not differ between patients exposed to blood stored 8-35 days and patients exposed to blood stored 7 days or less (in patients with blood group A or O: 0.92, 0.74-1.15, p=0.48; in all patients: 0.90, 0.73-1.10, p=0.29). INTERPRETATION These data provide evidence that transfusion of blood stored for longer than 35 days has no effect on in-hospital mortality, which suggests that current approaches to blood storage and inventory management are reasonable. FUNDING Canadian Institutes for Health Research, Canadian Blood Services, and Health Canada.
Mortality outcomes in patients transfused with fresher versus older red blood cells: a meta-analysis
Vox Sanguinis. 2017;112((3):):268-278
BACKGROUND Among transfused patients, the effect of the duration of red blood cell storage on mortality remains unclear. This study aims to compare the mortality of patients who were transfused with fresher versus older red blood cells. METHODS We performed an updated systematic search in the CENTRAL, MEDLINE, EMBASE and CINAHL databases, from January 2015 to October 2016. RCTs of hospitalized patients of any age comparing transfusion of fresher versus older red blood cells were eligible. We used a random-effects model to calculate pooled risk ratios (RRs) with corresponding 95% confidence interval (CI). RESULTS We identified 14 randomized trials that enrolled 26 374 participants. All-cause mortality occurred in 1219 of 9531 (12.8%) patients who received a transfusion of fresher red blood cells and 1810 of 16 843 (10.7%) in those who received older red blood cells (RR: 1.04, 95% CI: 0.98-1.12, P = 0.90, I2 = 0%, high certainty for ruling out benefit of fresh blood, moderate certainty for ruling out harm of fresh blood). In six studies, in-hospital death occurred in 691 of 7479 (9.2%) patients receiving fresher red cells and 1291 of 14 757 (8.8%) receiving older red cells (RR: 1.06, 95% CI: 0.97-1.15, P = 0.81, I2 = 0%, high certainty for ruling out benefit of fresh blood, moderate certainty for ruling out harm of fresh blood). CONCLUSION Transfusion of fresher red blood cells does not reduce overall or in-hospital mortality when compared with older red blood cells. Our results support the practice of transfusing patients with the oldest red blood cells available in the blood bank.
Informing Fresh versus Old Red Cell Management (INFORM) trial: a large international pragmatic randomized trial
Transfusion. 2016;56((S4)):5A.. p6-030a.
Effect of short-term vs. long-term blood storage on mortality after transfusion
The New England Journal of Medicine. 2016;375((20):):1937-1945
Background Randomized, controlled trials have suggested that the transfusion of blood after prolonged storage does not increase the risk of adverse outcomes among patients, although most of these trials were restricted to high-risk populations and were not powered to detect small but clinically important differences in mortality. We sought to find out whether the duration of blood storage would have an effect on mortality after transfusion in a general population of hospitalized patients. Methods In this pragmatic, randomized, controlled trial conducted at six hospitals in four countries, we randomly assigned patients who required a red-cell transfusion to receive blood that had been stored for the shortest duration (short-term storage group) or the longest duration (long-term storage group) in a 1:2 ratio. Only patients with type A or O blood were included in the primary analysis, since pilot data suggested that our goal of achieving a difference in the mean duration of blood storage of at least 10 days would not be possible with other blood types. Written informed consent was waived because all the patients received treatment consistent with the current standard of care. The primary outcome was in-hospital mortality, which was estimated by means of a logistic-regression model after adjustment for study center and patient blood type. Results From April 2012 through October 2015, a total of 31,497 patients underwent randomization. Of these patients, 6761 who did not meet all the enrollment criteria were excluded after randomization. The primary analysis included 20,858 patients with type A or O blood. Of these patients, 6936 were assigned to the short-term storage group and 13,922 to the long-term storage group. The mean storage duration was 13.0 days in the short-term storage group and 23.6 days in the long-term storage group. There were 634 deaths (9.1%) in the short-term storage group and 1213 (8.7%) in the long-term storage group (odds ratio, 1.05; 95% confidence interval [CI], 0.95 to 1.16; P=0.34). When the analysis was expanded to include the 24,736 patients with any blood type, the results were similar, with rates of death of 9.1% and 8.8%, respectively (odds ratio, 1.04; 95% CI, 0.95 to 1.14; P=0.38). Additional results were consistent in three prespecified high-risk subgroups (patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer). Conclusions Among patients in a general hospital population, there was no significant difference in the rate of death among those who underwent transfusion with the freshest available blood and those who underwent transfusion according to the standard practice of transfusing the oldest available blood. (Funded by the Canadian Institutes of Health Research and others; INFORM Current Controlled Trials number, ISRCTN08118744 .).
Interventions to reduce blood loss from laboratory testing in critically ill patients and impact on transfusion: a systematic review
Journal of Thrombosis and Haemostasis. 2015;13((Suppl. 2)):974-975.. Abstract No. PO616-WED.
Interventions to reduce blood loss from laboratory testing in critically ill patients and impact on transfusion: a systematic review
Blood. 2015;: Abstract No. 40.
Advance targeted transfusion in anemic cardiac surgical patients for kidney protection: an unblinded randomized pilot clinical trial
INTRODUCTION : Acute kidney injury (AKI) is a serious complication of cardiac surgery, and preoperative anemia and perioperative erythrocyte transfusion are important risk factors. Prophylactic erythrocyte transfusion in anemic patients may, therefore, protect against AKI. METHODS : In this unblinded, parallel-group, randomized pilot trial, 60 anemic patients (hemoglobin 10-12 g/dL) undergoing cardiac surgery with cardiopulmonary bypass were randomized (1: 1) to prophylactic transfusion (2 units of erythrocytes transfused 1 to 2 days before surgery (n = 29) or standard of care (transfusions as indicated; n = 31). Between-group differences in severity of perioperative anemia, transfusion, and AKI (more than 25% drop in estimated glomerular filtration rate) were measured. The relationships between transfusion, iron levels, and AKI were also measured. RESULTS : Perioperative anemia and erythrocyte transfusions were lower in the prophylactic transfusion group--median (25th, 75th percentiles) for nadir hemoglobin was 8.3 (7.9, 9.1) versus 7.6 (6.9, 8.2) g/dL (P = 0.0008) and for transfusion was 0 (0, 2) versus 2 (1, 4) units (P = 0.0002)--but between-group AKI rates were comparable (11 patients per group). In 35 patients with iron studies, perioperative transfusions were directly related to postoperative transferrin saturation (correlation coefficient 0.6; P = 0.0002), and high (more than 80%) transferrin saturation was associated with AKI (5/5 vs. 8/30; P = 0.005), implicating transfusion-related iron overload as a cause of AKI. CONCLUSIONS : In anemic patients, prophylactic erythrocyte transfusion reduces perioperative anemia and erythrocyte transfusions, and may reduce plasma iron levels. Adequately powered studies assessing the effect of this intervention on AKI are warranted.
The effect of blood storage duration on in-hospital mortality: a randomized controlled pilot feasibility trial
BACKGROUND Whether the duration of storage of blood has an impact on patient outcomes remains controversial. The objective was to determine feasibility of a comparative effectiveness trial to evaluate duration of storage of blood before transfusion on in-hospital mortality. STUDY DESIGN AND METHODS A single-center randomized controlled trial was performed at an acute care hospital in Canada between June and December 2010, involving consecutive hospitalized patients needing blood transfusion. Patients (n=910) were randomly assigned in a 1:2 ratio to receive freshest available versus standard-issue (oldest available) blood. Four feasibility criteria were measured: proportion of eligible patients randomized, contrast in age of blood between treatment groups, real-time data acquisition, and trial impact on blood outdating. In-hospital mortality was also reported. RESULTS A total of 1075 of 1129 patients (95.2%) were eligible and 910 of 1075 (84.7%) were randomized: 309 received freshest available blood (1157 units), and 601 received standard-age blood (2369 units). Contrast in mean age of the oldest blood transfused between groups was 14.6 days: 12.0 (standard deviation [SD], 6.8) days in the fresh arm and 26.6 (SD, 7.8) days in the standard arm. Weekly recruitment and event reporting were achieved for all patients. The blood outdate rate was 0.10%. In-hospital mortality was 10.5%: 35 deaths (11.3%) in the fresh arm and 61 deaths (10.1%) in the standard arm (odds ratio, 1.13; 95% confidence interval [CI], 0.73, 1.76). CONCLUSION It is feasible to conduct a large comparative effectiveness trial comparing the effect of freshest available versus standard-issue blood on in-hospital mortality. The wide CI around the estimate for in-hospital mortality supports the need for a large trial. 2012 American Association of Blood Banks.
Can we do a 25,000 patient pragmatic study to address the age of blood and mortality controversy? A pilot to determine feasibility