Transfusion Of Older Red Blood Cells Research Articles

Effect of storage duration on outcome of patients receiving red blood cell in emergency department.

The effect of the duration of red blood cell (RBC) storage on the outcomes of transfused patients remains controversial, and studies on patients in the emergency department (ED) are limited. This study aimed to determine the association between RBC storage duration and outcomes of patients receiving transfusions in the ED. For RBCs issued to patients in the ED between 2017 and 2022, the storage period of the RBC and data on the transfused patient were obtained. Patients were divided into fresh (≤ 7 days) and old (> 7 days) RBC groups, and the associations between storage duration, outcomes, and laboratory changes were evaluated. There was no significant difference in outcomes between the two groups in the 28-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] 0.75-1.10, P = 0.320) and the length of stay (fresh 13.5 ± 18.1 vs. old 13.3 ± 19.8, P = 0.814). Regarding changes in laboratory test results, the increase in hemoglobin and hematocrit levels was not affected by the storage durations. The study revealed that transfusion of older RBCs is not associated with inferior outcomes or adverse clinical consequences when compared to that of fresh RBCs in patients in the ED.

Hemolytic anemia blunts the cytokine response to transfusion of older red blood cells in mice and dogs.

Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions. C57BL/6 mouse cohorts were infused with anti-TER119 antibody to induce hemolysis, rabbit anti-platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client-owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (≤7 days) or old (≥21 days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)-1 levels were assessed at defined times after transfusion. Prior immune-mediated hemolysis blunted the MCP-1 response to stored RBC transfusion in mice (361 ± 111 pg/ml vs. 6836 ± 1528 pg/ml in mice with immune hemolysis vs. ITP, respectively; mean ± SD; p< .0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs. These data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.

Association between storage age of transfused red blood cells and clinical outcomes in critically ill adults: A meta-analysis of randomized controlled trials

ObjectivesA meta-analysis was performed to assesses the effect of storage age of transfused red blood cells (RBCs) upon clinical outcomes in critically ill adults. MethodsA comprehensive search was conducted in the PubMed, OVID, Web of Science and Cochrane databases for randomized controlled trials (RCTs) comparing the transfusion of fresher versus older RBCs in critically ill adults from database inception to December 2017. The primary endpoint was short-term mortality, and the secondary endpoints were the duration of intensive care unit (ICU) and hospital stay. The pooled odds ratios (OR) and mean differences (MD) were calculated using Stata/SE 11.0. ResultsA total of six RCTs were identified, of which four were multicenter studies, while two were single-center trials. The pooled results indicated that the transfusion of fresher RBCs was not associated to a decrease in short-term mortality compared with the transfusion of older RBCs (random-effects OR=1.04, 95% confidence interval (CI): 0.96–1.13, P=0.312; I2=0.0%; six trials; 18240 patients), regardless of whether the studies were of a multi-center (random-effects OR=1.04, 95% CI: 0.96–1.13, P=0.292; I2=0.0%) or single-center nature (random-effects OR=1.16, 95% CI: 0.28–4.71, P=0.839; I2=56.7%), or with low risk of bias (random-effects OR=1.04, 95% CI: 0.94–1.16, P=0.445; I2=0.0%). In addition, the transfusion of fresher RBCs did not reduce the geometric mean duration of ICU stay (1.0% increase in geometric mean, 95% CI: −3.0 to 5.1%, P=0.638; I2=81.5%; four trials; 7550 patients) or the geometric mean duration of hospital stay (0.0% increase in geometric mean, 95% CI: −3.9 to 4.1%, P=0.957; I2=7.4%; four trials; 7550 patients) compared with the transfusion of older RBCs. ConclusionsThe transfusion of fresher RBCs compared with older RBCs was not associated to better clinical outcomes in critically ill adults.

Macrophage Recycling of Red Blood Cells and Iron Following Transfusion

Red blood cells (RBCs) destined for transfusion can be refrigerator stored for up to 42 days prior to transfusion. During this ex vivo storage period, RBCs are progressively damaged in a process that is termed the RBC storage lesion. The end result of this storage lesion is that with longer durations of storage prior to transfusion, an increased number of storage-damaged RBCs are cleared from the circulation via extravascular hemolysis. Studies in mice, dogs, and humans suggest that transfusion of older, stored RBCs, but not fresh RBCs, produce acute elevations in circulating markers of extravascular hemolysis (e.g., indirect bilirubin and transferrin saturation). Furthermore, hepcidin is induced in humans approximately 4-6 hours after transfusion and likely results in the return to baseline serum iron levels by 20-hours following transfusion. This is associated with a concomitant rise in serum ferritin levels, suggesting that hepcidin-induced degradation of ferroportin results in intracellular storage of iron within macrophages. Furthermore, the rate at which the macrophages release iron can be greater than the capacity of circulating transferrin to handle that iron, resulting in production of non-transferrin-bound iron. This pathogenic form of iron may be a cause of adverse effects in transfusion recipients. Indeed, in animal models, iron availability is associated with increased morbidity and mortality from infectious challenges with certain bacteria. A human study comparing transfusion of a single unit of RBCs following 1, 2, 3, 4, 5, or 6 weeks of storage suggests that the RBC storage lesion does not develop linearly and is only capable of inducing non-transferrin-bound iron production in healthy adult recipients following 5-6 weeks of storage. However, this relationship may differ in critically-ill populations. Furthermore, there is significant variability among blood donors in their RBC quality following storage. There are likely to be both genetic and environmental causes to this variability. Some of these causes may be donor glucose-6-phosphate dehydrogenase status, iron status, and/or dietary lipid content. In addition, in animal models, the clearance of a bolus of storage-damaged RBCs is associated with a pro-inflammatory cytokine response. Although this has yet to be demonstrated in studies using healthy adult human volunteers, studies in pediatric patient populations suggest that RBC transfusions may be associated with a pro-inflammatory response in this vulnerable population. The precise mechanism of inflammation following transfusion, and its clinical implications, has yet to be resolved. Finally, recent randomized clinical trials suggest that there are no clinical outcome differences when patients are randomized to receiving transfusions of fresh RBCs as opposed to the standard of care. Perhaps the RBC storage lesion has no clinical consequences to the transfusion recipient. However, these studies were not powered nor designed to test the effects of transfusion of RBCs during the final week of storage, in which studies suggest the effects would be most striking. Furthermore, many of the recipients in these studies already suffered from baseline hemolysis (e.g., from cardiac pump induced hemolysis, malaria, and sickle cell disease). It is unlikely that the added hemolysis from a transfusion of older RBCs would have a clinical impact given the level of baseline hemolysis from other causes observed in these patient populations. Thus, whether there are pathophysiologic consequences to the clearance of storage-damaged RBCs is still debatable. DisclosuresNo relevant conflicts of interest to declare.

Association between storage age of transfused red blood cells and clinical outcomes in critically ill adults: A meta-analysis of randomized controlled trials.

A meta-analysis was performed to assesses the effect of storage age of transfused red blood cells (RBCs) upon clinical outcomes in critically ill adults. A comprehensive search was conducted in the PubMed, OVID, Web of Science and Cochrane databases for randomized controlled trials (RCTs) comparing the transfusion of fresher versus older RBCs in critically ill adults from database inception to December 2017. The primary endpoint was short-term mortality, and the secondary endpoints were the duration of intensive care unit (ICU) and hospital stay. The pooled odds ratios (OR) and mean differences (MD) were calculated using Stata/SE 11.0. A total of six RCTs were identified, of which four were multicenter studies, while two were single-center trials. The pooled results indicated that the transfusion of fresher RBCs was not associated to a decrease in short-term mortality compared with the transfusion of older RBCs (random-effects OR=1.04, 95% confidence interval (CI): 0.96-1.13, P=0.312; I2=0.0%; six trials; 18240 patients), regardless of whether the studies were of a multi-center (random-effects OR=1.04, 95% CI: 0.96-1.13, P=0.292; I2=0.0%) or single-center nature (random-effects OR=1.16, 95% CI: 0.28-4.71, P=0.839; I2=56.7%), or with low risk of bias (random-effects OR=1.04, 95% CI: 0.94-1.16, P=0.445; I2=0.0%). In addition, the transfusion of fresher RBCs did not reduce the geometric mean duration of ICU stay (1.0% increase in geometric mean, 95% CI: -3.0 to 5.1%, P=0.638; I2=81.5%; four trials; 7550 patients) or the geometric mean duration of hospital stay (0.0% increase in geometric mean, 95% CI: -3.9 to 4.1%, P=0.957; I2=7.4%; four trials; 7550 patients) compared with the transfusion of older RBCs. The transfusion of fresher RBCs compared with older RBCs was not associated to better clinical outcomes in critically ill adults.

Preischemic transfusion of old packed RBCs exacerbates early-phase warm hepatic ischemia reperfusion injury in rats

BackgroundHepatic innate immune cells are considered to play a central role in the early phase of hepatic ischemia reperfusion (IR) injury. Transfusion of old red blood cells (RBCs) is known to prime immune cells, and transfusion before IR may exacerbate liver injury because of the expected hyperresponsiveness of immune cells. Materials and methodsTwenty-four Sprague–Dawley rats were divided into four groups: sham operation (Sham); hepatic IR only (IR Control); and two transfusion groups, preischemic (Pre-T) and postischemic (Post-T), in which allogeneic RBCs stored for 2 weeks were transfused before hepatic IR or after reperfusion, respectively. Partial hepatic ischemia was induced for 90 min, and reperfusion was allowed for 120 min. Serum alanine transaminase levels, area of necrosis, and apoptotic cells were then assessed. Inflammatory (tumor necrosis factor alpha, interleukin 1 beta [IL-1β], IL-6, IL-10, and cyclooxygenase 2) and oxidative mediators (heme oxygenase 1, superoxide dismutase, and glutathione peroxidase 1) were assessed for elucidating the relevant mechanisms underlying the hepatic injury. ResultsPre-T, but not Post-T, showed increased serum alanine transaminase levels than IR Control (P < 0.05). Area of necrosis was more severe in Pre-T than in IR Control or Post-T (P < 0.01), and apoptotic cells were also more abundant in Pre-T than in IR Control (P < 0.01). tumor necrosis factor alpha and IL-6 levels were higher in Pre-T than in IR Control or Post-T (P < 0.05), with no significant difference in cytoprotective protein levels. ConclusionsPreischemic transfusion of old RBCs aggravated hepatic injury. Inflammatory cytokines seemed to play a crucial role in liver injury exacerbation. Our results indicate that transfusion before hepatic ischemia may be detrimental.

Perioperative Red Blood Cell Transfusion: What We Do Not Know.

Objective:Blood transfusion saves lives but may also increase the risk of injury. The objective of this review was to evaluate the possible adverse effects related to transfusion of red blood cell (RBC) concentrates stored for prolonged periods.Data Sources:The data used in this review were mainly from PubMed articles published in English up to February 2015.Study Selection:Clinical and basic research articles were selected according to their relevance to this topic.Results:The ex vivo changes to RBC that occur during storage are collectively called storage lesion. It is still inconclusive if transfusion of RBC with storage lesion has clinical relevance. Multiple ongoing prospective randomized controlled trials are aimed to clarify this clinical issue. It was observed that the adverse events related to stored RBC transfusion were prominent in certain patient populations, including trauma, critical care, pediatric, and cardiac surgery patients, which leads to the investigation of underlying mechanisms. It is demonstrated that free hemoglobin toxicity, decreasing of nitric oxide bioavailability, and free iron-induced increasing of inflammation may play an important role in this process.Conclusion:It is still unclear whether transfusion of older RBC has adverse effects, and if so, which factors determine such clinical effects. However, considering the magnitude of transfusion and the widespread medical significance, potential preventive strategies should be considered, especially for the susceptible recipients.

Red blood cell storage and alloimmunization: a fact or a myth?

Red blood cell (RBC) alloimmunization is a significant clinical complication of transfusion-dependent patients; it is related to delays in obtaining matched blood as well as potentially life-threatening delayed hemolytic transfusion reactions (DHTRs), autoantibody formation, and hyperhemolysis syndrome.1 Because of its critical significance, the phenomenon of RBC alloimmunization has been investigated in a variety of settings. With a better understanding of the factors that predispose to RBC alloimmunization, it is possible to devise strategies for blood transfusions that reduce the risk of alloimmunization and adverse reactions to transfusion. Clinical and biological factors such as disease state, human leukocyte antigen (HLA) polymorphisms, underlying inflammation, immunogenicity of the antigens and patient age are independent variables involved in RBC alloimmunization.2 In addition, stored leukocyte-reduced RBCs have been reported to produce higher rates of immunogenicity than fresh blood in murine models.3 These findings led to speculate that the transfusion of older RBCs might create a cytokine burst that predisposes a human recipient to RBC alloimmunization and thus raised the interest of some groups to perform studies in humans. Some recent studies have suggested that RBC storage length is associated with adverse patient outcomes ranging from death to pneumonia to increased length of hospital and intensive care unit stays.4,5 RBC alloimmunization was chosen as an outcome in these studies because it can be both medically and logistically problematic.6,7 By identifying associations, it may be possible to support or not support changing

Massive transfusion protocol activation does not result in preferential use of older red blood cells.

Widespread, anecdotal belief exists that patients receiving massive transfusion, particularly those for whom a massive transfusion protocol (MTP) is activated, are more likely to receive older red blood cells (RBCs). Retrospective review of blood bank records from calendar year 2011 identified 131 patients emergently issued ≥10 RBC units (emergency release (ER)) prior to obtaining a type and screen. This cohort was subclassified based on whether there was MTP activation. For comparison, 176 identified patients transfused with ≥10 RBC units in a routine fashion over 24 hours represented the nonemergency release (nER) cohort. Though the median age of ER RBCs was 5 days older than nER RBCs (ER 20, nER 15 days, P < 0.001), both fell within the third week of storage. Regardless of MTP activation, transfused ER RBCs had the same median age (MTP 20, no-MTP 20 days, P = 0.069). In the ER cohort, transition to type-specific blood components increased the median age of transfused RBC units from 17 to 36 days (P < 0.001). These data refute the anecdotal belief that MTP activation results in transfusion of older RBCs. However, upon transition to type-specific blood components, the age of RBCs enters a range in which it is hypothesized that there may be a significant effect of storage age on clinical outcomes.

Effect of perioperative transfusion of old red blood cells on postoperative complications after free muscle sparing transverse rectus abdominis myocutaneous flap surgery for breast reconstruction

Transfusion with old red blood cells (RBCs) was associated with adverse clinical outcomes. The effect of perioperative transfusion of old RBCs on postoperative complications after free muscle sparing transverse rectus abdominis myocutaneous (TRAM) flap surgery was retrospectively investigated. Two hundred sixty-one patients undergoing breast reconstruction were assigned to two groups: no transfusion and transfusion groups. Transfused patients were further divided according to the RBC storage duration (fresh, ≤14 days; old, >14 days). Postoperative complications such as vascular thrombosis, hematoma, and flap congestion were noted. Patients who received old blood (n = 34), compared with those received fresh blood (n = 40) or no transfusion (n = 187), had a higher incidence of postoperative complications (44.1% vs. 20.0% or 12.8%, P < 0.05). Perioperative transfusion of old RBCs can be associated with an increase in postoperative complications after free muscle sparing TRAM flap surgery.

Aged erythrocytes: a fine wine or sour grapes?

Blood transfusion saves many lives but carries significant risk of injury. Currently, red blood cell (RBC) concentrates can be stored up to 42 days. Concerns have recently been raised about the safety and efficacy of transfusing stored RBCs. Refrigerated storage results in a 'storage lesion' that is reflected by metabolic derangements, RBC shape modification, rheological changes, oxidative injury to lipids and proteins, alterations in oxygen affinity and delivery, increased adhesion of RBCs to endothelial cells, and accumulation of bioactive substances in storage media. In animal models, transfusion of aged, but not fresh, RBCs induces organ injury, inflammation, coagulopathy, and impaired oxygen delivery. A number of clinical studies, mostly observational or retrospective and from a single centre, have reported an association between transfusion of older RBCs and increased clinically significant outcomes, such as increased morbidity and mortality in certain patient populations, including trauma, critical care, and cardiac surgery. Others, however, have failed to indicate an influence of RBC age on outcome. The quality of evidence is currently too poor to make recommendations to change current transfusion practice; however, the transfusion community looks forward to the results of randomized trials currently addressing the long-standing question regarding the effects of RBC storage on clinically significant outcomes.

Relationship between red cell storage duration and outcomes in adults receiving red cell transfusions: a systematic review

IntroductionThe duration of red blood cell (RBC) storage before transfusion may alter RBC function and supernatant and, therefore, influence the incidence of complications or even mortality.MethodsA MEDLINE search from 1983 to December 2012 was performed to identify studies reporting age of transfused RBCs and mortality or morbidity in adult patients.ResultsFifty-five studies were identified; most were single-center (93%) and retrospective (64%), with only a few, small randomized studies (eight studies, 14.5%). The numbers of subjects included ranged from eight to 364,037. Morbidity outcomes included hospital and intensive care unit (ICU) length of stay (LOS), infections, multiple organ failure, microcirculatory alterations, cancer recurrence, thrombosis, bleeding, vasospasm after subarachnoid hemorrhage, and cognitive dysfunction. Overall, half of the studies showed no deleterious effects of aged compared to fresh blood on any endpoint. Eleven of twenty-two (50%) studies reported no increased mortality, three of nine (33%) showed no increased LOS with older RBCs and eight of twelve (66%) studies showed no increased risks of organ failure. Ten of eighteen (55%) studies showed increased infections with transfusion of older RBCs. The considerable heterogeneity among studies and numerous methodological flaws precluded a formal meta-analysis.ConclusionsIn this systematic review, we could find no definitive argument to support the superiority of fresh over older RBCs for transfusion.

Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients.

Forward This document aims to summarize the current literature guiding the use of red cell transfusion in critically ill patients and provides recommendations to support clinicians in their day-to-day practice. Critically ill patients differ in their age, diagnosis, co-morbidities, and severity of illness. These factors influence their tolerance of anaemia and alter the risk to benefit ratio of transfusion. The optimal management for an individual may not fall clearly within our recommendations and each decision requires a synthesis of the available evidence and the clinical judgment of the treating physician. This guideline relates to the use of red cells to manage anaemia during critical illness when major haemorrhage is not present. A previous British Committee for Standards in Haematology (BCSH) guideline has been published on massive haemorrhage (Stainsby et al, 2006), but this is a rapidly changing field. We recommend readers consult recent guidelines specifically addressing the management of major haemorrhage for evidence-based guidance. A subsequent BCSH guideline will specifically cover the use of plasma components in critically ill patients.

Red blood cell storage is associated with length of stay and renal complications after cardiac surgery

The association of red blood cell (RBC) storage on morbidity outcome after cardiac surgery is debated. We sought to clarify the association of the age of transfused blood on outcome in patients undergoing cardiac surgery. Data were drawn from a prospective, observational cohort study of morbidity outcome in patients undergoing cardiac surgery. Blood transfusion data were obtained retrospectively via the Trust blood bank electronic records. Old blood was defined as more than 14 days old. The primary outcome measure was postoperative length of stay (PLOS). Secondary outcome measures included renal failure and morbidity as defined within the postoperative morbidity survey. A total of 176 (39.6%) of 444 participants received a blood transfusion. Patients transfused with new blood had a reduced PLOS compared with patients receiving exclusively old or any old blood (old blood ± new blood; 7 days vs. 8 days, p = 0.04 and vs. 10 days, p = 0.002, respectively). In patients who only had 1 unit transfused, PLOS was longer in those receiving only old blood compared with those receiving only new blood (8 days vs. 6 days, p = 0.02) with a 3.8-fold risk of longer stay. Compared with patients receiving exclusively new blood, patients receiving any old blood had a higher incidence of new renal complications (65.7% vs. 43.9%, p = 0.008). Each 1-day increase in storage was associated with a 7% increase in risk of new renal complications. Our data support previous suggestions of an association between transfusion of older RBCs and poorer outcome in cardiac surgery patients. Randomized controlled trials are required to determine the true causal nature of any such association.

Transfusions of Red Blood Cells Stored for 40–42 Days Induce Circulating Non-Transferrin-Bound Iron (NTBI) In Healthy Adults

AbstractAbstract 662To compare the effects on iron metabolism of transfusion of packed red blood cells (RBCs) after prolonged (40-42 days) and short-term (3–7 days) storage, we prospectively studied 9 healthy adults. Each volunteer donated a standard, leukoreduced, double RBC unit by automated apheresis and was then transfused with the first autologous RBC unit after 3–7 days of storage and the second after 40–42 days of storage. Timed blood samples were obtained just before each transfusion and immediately, 1, 2, 4, 24, and 72-hours after transfusion. Plasma non-transferrin bound iron (NTBI) was quantified by an ultrafiltration assay, serum hepcidin determined by an immunoassay, and complete blood counts and other laboratory measures obtained by standard methods. For each analyte, differences after transfusion of the older and fresher RBCs were evaluated by 2-way ANOVA with a Bonferroni post-test. At 24 hours after transfusion, similar increases in mean hemoglobin concentration were found with the older (0.83 ± 0.54 (SD) g/dL) and fresher (0.74 ± 0.58 (SD) g/dL) units (p=0.30). At 4 hours after transfusion of older RBCs there was a significant, ~3-fold increase over baseline in mean serum iron (by 160 ± 99 mcg/dL with older vs. −7 ± 25 mcg/dL with fresher RBCs, p<0.001), along with ~2-fold rise in mean total serum bilirubin (by 0.52 ± 0.37 mg/dL with older vs. −0.09 ± 0.18 mg/dL with fresher RBCs, p<0.001). There were no significant differences in circulating lactate dehydrogenase or haptoglobin at any time. The significant increases in mean transferrin saturation (p<0.001) and mean change in plasma NTBI (p<0.001) seen after transfusions of older RBCs are shown in the accompanying Figure. [Display omitted] After transfusion of fresher and older blood, mean serum hepcidin concentrations were not significantly different at any time and no significant differences were found in mean serum C-reactive protein (CRP) or interleukin (IL)-6 levels. Current FDA standards allow refrigerated RBC units to be stored for up to 42 days before transfusion based on the criteria that, on average, less than 25% of the transfused RBCs will be cleared from the circulation in the first 24 hours. In critically ill patients, observational studies identified increases in serious infections, multi-organ failure, and mortality associated with transfusion of older stored RBCs, but the underlying mechanisms have yet to be determined. In healthy volunteers, our results indicate that transfusions of RBCs stored for 3–7 days did not significantly increase serum iron or induce the appearance of plasma NTBI. In contrast, transfusion of RBCs stored for 40–42 days significantly increased serum iron and transferrin saturation and produced substantial amounts of plasma NTBI, in association with the apparently extravascular clearance of a subpopulation of the transfused RBCs. Plasma NTBI can promote bacterial growth and induce oxidative injury. The observed increases in plasma NTBI in healthy volunteers after transfusion of older stored RBCs produced no clinically-evident adverse effects. Nonetheless, in critically ill patients, increases in plasma NTBI may enhance the risk of sepsis, multi-organ failure, and death. Disclosures:Olbina:Intrinsic LifeSciences LLC: Employment. Westerman:Intrinsic Life Sciences: Employment, Membership on an entity's Board of Directors or advisory committees.

BLOOD COMPONENTS: Meta‐analysis of clinical studies of the purported deleterious effects of “old” (versus “fresh”) red blood cells: are we at equipoise?

BACKGROUND: A meta‐analysis examined whether the available data support an adequate suspicion that transfusion of old red blood cells (RBCs) is associated with increased mortality, organ failure, infection, prolonged mechanical ventilation, and prolonged stay in the hospital or the intensive care unit. Such suspicion is required for intentionally exposing patients enrolled in randomized controlled trials (RCTs) to the known or probable—but rare—risks of old RBCs, to document (and prevent) purported common adverse effects of old RBCs.STUDY DESIGN AND METHODS: Observational studies presenting adjusted results were eligible for analysis if the adequacy of the adjustment for confounding factors could be assessed. Three RCTs and 24 observational studies were retrieved. Medically and statistically homogeneous studies were integrated by fixed‐effects methods. Otherwise homogeneous studies conducted in different clinical settings were integrated by random‐effects methods.RESULTS: Based on “as‐treated” analysis, transfusion of old RBCs was associated with a significant reduction in mortality (summary odds ratio, 0.38; 95% confidence interval, 0.14‐0.99; p &lt; 0.05) across two small RCTs. Integration of adjusted findings on the same outcome, from observational studies conducted in the same setting, produced summary results that were either negative (in six analyses) or impossible to evaluate owing to uncontrolled confounding by the number of transfused RBCs (in two analyses).CONCLUSION: The available data do not support an adequate suspicion that old RBCs may be associated with common adverse morbidity and/or mortality outcomes, so as to justify exposing experimental subjects to the other known or probable—but rare—risks of old RBCs.

Age of Red Blood Cell Units Transfused in Canada.

Abstract 3143Poster Board III-80 BackgroundDuring storage, red blood cells (RBCs) undergo well-described biochemical and biomechanical changes, termed the red cell storage lesion. These changes may affect the ability of stored RBCs to deliver oxygen or have other adverse consequences. The transfusion of older RBCs has been associated with increased morbidity/mortality, and planned or on-going randomized controlled trials are exploring a possible causal relationship between the age of RBCs and mortality/morbidity. However, the age-related characteristics of the RBCs units in hospital inventories and of the RBCs units transfused are largely unknown. MethodA descriptive observational study from 9 centres from 5 Canadian provinces was conducted. Using a randomly generated schedule, data was collected on one weekday for 30 consecutive weeks. Reports of the RBCs inventories and the transfused RBCs units for all ABO and Rh blood groups were collected and analyzed. ResultsAcademic centers contributed more than half of the collected data, both for inventory and for transfused units. Overall, the median age of RBCs units in inventory was 14 days (IQR=10-20) and their median age upon transfusion was 16 days (IQR=12-22). The cumulative proportion of younger blood (less than 8 days) in inventory was 9% (range for individual centres: 5 to 20%) for units in inventory and 5% (range for individual centres: 1 to 17%) for transfused units. The cumulative proportion of older blood (more than 28 days) was 8% (range for individual centres: 6 to 14%) for units in inventory, and 13% (range for individual centres: 9 to 23%) for transfused units. Community centres tended to have the largest proportion of younger units transfused (12%) as well as in inventory (14%). ConclusionThis study provides important data that may contribute to decision-making regarding blood bank inventory management and age-based transfusion practices. If the results of ongoing studies demonstrate an adverse effect from transfusing older RBCs, then significant changes to the inventory management may be required. In Canada, shortening the shelf-life for storage of RBC units to 28 days may be less problematic, but restricting the age of RBCs transfused to less than 8 days for all RBC units may pose significant challenges. DisclosuresTinmouth:Canadian Blood Services: Consultancy; Novartis: Research Funding; CSL: Research Funding; Bayer: Research Funding; Wyeth: Research Funding.