Alan Tinmouth

Red blood cell transfusion: A Clinical practice guideline from the AABB

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).

Clinical consequences of red cell storage in the critically ill

Red cell (RBC) transfusions are a potentially life‐saving therapy employed during the care of many critically ill patients to replace losses in hemoglobin to maintain oxygen delivery to vital organs. During storage, RBCs undergo a series of biochemical and biomechanical changes that reduce their survival and function. Additionally, accumulation of other biologic by‐products of RBC preservation may be detrimental to recipients of blood transfusions. Laboratory studies and an increasing number of observational studies have raised the possibility that prolonged RBC storage adversely affects clinical outcomes. In this article, the laboratory and animal experiments evaluating changes to RBCs during prolonged storage are reviewed. Subsequently, the clinical studies that have evaluated the clinical consequences of prolonged RBC storage are reviewed. These data suggest a possible detrimental clinical effect associated with the transfusion of stored RBCs; randomized clinical trials further evaluating the clinical consequences of transfusing older stored RBCs are required.

Age of Transfused Blood in Critically Ill Adults

BACKGROUND Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).

Continuous Multi-Parameter Heart Rate Variability Analysis Heralds Onset of Sepsis in Adults

Background Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV) has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis. Methodology/Principal Findings We monitored heart rate continuously in adult bone marrow transplant (BMT) patients (n = 21) beginning a day before their BMT and continuing until recovery or withdrawal (12±4 days). We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline) over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment). Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25%) reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14), wavelet HRV demonstrated a 25% drop from baseline 35 h prior to sepsis on average. For 3 out of 3 non-infected patients, all measures, except root mean square successive difference and entropy, showed no significant reduction. Significant correlation was present amongst these HRV metrics for the entire population. Conclusions/Significance Continuous HRV monitoring is feasible in ambulatory patients, demonstrates significant HRV alteration in individual patients in association with, and prior to clinical diagnosis and treatment of sepsis, and merits further investigation as a means of providing early warning of sepsis.

Transfusion of leukoreduced red blood cells may decrease postoperative infections: two meta-analyses of randomized controlled trials

PurposeTo evaluate the efficacy and effectiveness of red blood cell leukoreduction in reducing postoperative infection, mortality and cancer recurrence, two meta-analyses of randomized controlled trials (RCTs) were conducted.MethodsA systematic search of the scientific literature was conducted. The pooled relative risk ratio (RR) of developing an adverse postoperative outcome with either leukoreduced or non-leukoreduced blood was calculated using a random effects model. To better estimate the efficacy of leukoreduction, a second analysis of transfused patients only was conducted.ResultsTen RCTs met inclusion criteria and eight provided separate data for patients randomized and transfused. The mean percentage of patients randomized but not transfused was 34%. For postoperative infection, the overall pooled RR was 0.76 [(95% confidence interval (CI): 0.54–1.08] for the “all patients randomized” analysis. For the “only patients transfused” analysis, the pooled RR became clinically and statistically significant (RR = 0.60 (95% CI: 0.38–0.93). For mortality, the pooled RR for the “all patients randomized” analysis was 0.71 (95% CI: 0.45–1.13) and 0.61 (95% CI: 0.36–1.04) for the “only patients transfused” analysis. When analyzing either all patients randomized or all patients transfused, there was no statistically significant difference in cancer recurrence rates (one study only).ConclusionWe demonstrated that patients who were transfused leukoreduced red blood cells might benefit from a decrease in postoperative infections. A decrease in mortality may have been realized if more patients had been enrolled in the various randomized trials. Including all patients randomized, regardless of whether or not they were actually transfused diluted the observed clinical benefit of leukoreduction.RésuméObjectifDans le but d’évaluer l’efficacité de la réduction leucocytaire à diminuer l’infection postopératoire, la mortalité et la récurrence du cancer, nous avons réalisé deux méta-analyses d’études randomisées et contrôlées (ERC).MéthodeUne recherche systématique des publications scientifiques a été réalisée. Le risque relatif (RR) de subir des complications postopératoires avec du sang réduit ou non en leucocytes a été calculé au moyen d’un modèle à effets aléatoires. Afin de mieux estimer l’efficacité de la réduction leucocytaire, une seconde analyse des patients transfusés a été faite.RésultatsDix ERC répondaient aux critères d’inclusion et huit portaient sur des patients randomisés et transfusés. Le pourcentage moyen de patients randomisés mais non transfusés était de 34 %. Le RR global d’une infection postopératoire était de 0,76 [(intervalle de confiance de 95 % (IC) : 0,54–1,08] pour l’analyse où «tous les patients sont randomisés». Dans l’analyse des «seuls patients transfusés», le RR est devenu cliniquement et statistiquement significatif (RR = 0,60 (IC de 95 % : 0,38–0,93). Le RR de mortalité dans l’analyse de «tous les patients randomisés» était de 0,71 (IC 95 % : 0,45–1,13) et de 0,61 (IC 95 % : 0,36–1,04) dans l’analyse des «seuls patients transfusés». Les analyses de tous les patients randomisés et de tous les patients transfusés n’ont pas montré de différence statistiquement significative de récurrence du cancer (une étude seulement).ConclusionLes patients qui reçoivent du sang réduit en leucocytes sont moins susceptibles d’avoir des infections postopératoires. Une baisse de la mortalité aurait pu être réalisée si plus de patients avaient participé aux diverses études randomisées. Quand on inclut tous les patients randomisés, peu importe qu’ils aient été transfusés ou non, on observe une dilution des avantages cliniques de la réduction leucocytaire.

A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia

A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 x 10(9) platelets/product) or low-dose (150- < 300 x 10(9) platelets/product) platelets. The primary outcome (World Health Organization [WHO] bleeding > or = grade 2) was assessed daily through clinical examination, patient interview, and chart review. A WHO grade was assigned through adjudication. The Data Safety Monitoring Board stopped the study because the difference in the grade 4 bleeding reached the prespecified threshold of 5%. At this time, 129 patients had been randomized and 119 patients were included in the analysis (58 low dose; 61 standard dose). Three patients in the low-dose arm (5.2%) had grade 4 bleeds compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was 49.2% (30/61) in the standard-dose arm and 51.7% (30/58) in the low-dose group (relative risk [RR], 1.052; 95% confidence interval [CI], 0.737-1.502). A higher rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet transfusions resulted in this RCT being stopped. Whether this finding was due to chance or represents a real difference requires further investigation. These clinical studies are registered on (http://www.clinicaltrials.gov) as NCT00420914.

Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin : a case series analysis

BACKGROUND: This case series summarizes our observations of hemolytic reactions after the administration of large amounts of intravenous immune (gamma) globulin (IVIG).

The effectiveness of interventions to reduce physician's levels of inappropriate transfusion: what can be learned from a systematic review of the literature

T he use of blood components by health care providers has come under increased scrutiny in recent years.1 This is largely a consequence of the current focus on reducing health care costs combined with rising costs of specialized blood components, continuing problems with shortages of blood components, and concerns over the safety of blood transfusion.2,3 As a result of the increased scrutiny, attempts have been made to improve transfusion practices. One approach that has been taken is to reduce levels of unnecessary transfusions. Previous studies have demonstrated that there are important levels of transfusions considered to be inappropriate among health care providers.4 Interventions that can reduce the rate of these inappropriate transfusions have the potential to both improve health care outcomes and reduce costs by preventing donor exposures and preserving supply. Behavioral interventions, such as education and audit and/or feedback, have been used to change health care practices,5 and several studies have examined the effectiveness of these interventions to reduce inappropriate transfusion rates.6-14 However, evaluating the benefit of these interventions on reducing inappropriate transfusion can be challenging as these studies have varied considerably in study design and quality. In this article, systematic review techniques are used to identify these studies, present their characteristics, summarize their results, and appraise their quality. Based on these data, we derive conclusions on the usefulness of behavioral interventions to reduce inappropriate transfusion rates and provide recommendations on how best to evaluate the effectiveness of these interventions in future studies.

Transfusion rates vary significantly amongst Canadian medical centres

PurposeTo document variation of transfusion practice following repair of hip fracture or cardiac surgery, as well as those requiring intensive care following a surgical intervention or multiple trauma (high risk patients).MethodsWe documented rates of allogeneic red cell transfusion in 41,568 patients admitted to 11 hospitals across Canada between August 1998 and August 2000 as part of a retrospective observational cohort study. In the subgroup of 7,552 patients receiving red cells, we also compared mean nadir hemoglobin concentrations from centre to centre.ResultsThe overall rate of red cell transfusion was 38.7%, and ranged from 23.8% to 51.9% across centres among the 41,568 perioperative and critically ill patients. Women were more likely to be transfused (43.7%vs 35.3%,P < 0.0001), with higher rates of transfusion in eight of 11 centres. Compared to a chosen reference hospital having a crude transfusion rate near the median, the adjusted odds of transfusion ranged from 0.44 to 1.53 overall, from 0.42 to 1.22 in patients undergoing a hip fracture repair, from 0.72 to 3.17 in cardiac surgical patients undergoing cardiac surgery, and from 0.27 to 1.11 in critically ill and trauma patients. In the 7,552 transfused patients, the mean adjusted nadir hemoglobin was 74.0 ± 4.83 g·L-1 overall, and ranged from 66.9 ± 1.7 g·L-1 to 84.5 ± 1.6 g·L-1 across centres. Similar differences among centres were observed amongst hip fracture patients (71.2 ± 2.9 g·L-1 to 82.8 ± 1.7 g·L-1), cardiac surgical patients (65.7 ± 1.1 g·L-1 to 77.3 ± 1.0 g·L-1) and critically ill and trauma patients (66.1 ± 3.04 g·L-1 to 87.5 ± 2.5 g·L-1).ConclusionWe noted significant differences in the rates of red cell transfusion and nadir hemoglobin concentrations in various surgical and critical care settings.RésuméObjectifDocumenter les variations dans la pratique des transfusions à la suite d’une réparation de fracture de la hanche ou d’une intervention chirurgicale cardiaque, de même que des transfusions chez des patients de soins intensifs à la suite d’une intervention chirurgicale ou d’un polytraumatisme (patients à haut risque).MéthodeNous avons vérifié les taux de transfusion allogéniques chez 41 568 patients admis dans 11 hôpitaux canadiens entre août 1998 et août 2000 dans le cadre d’une étude rétrospective de cohorte par observation. Dans le sous-groupe de 7 552 patients transfusés, nous avons aussi comparé la moyenne des concentrations d’hémoglobine minimales d’un centre à l’autre.RésultatsLe taux global de transfusion de culots globulaires a été de 38,7 %, allant de 23,8 % à 51,9 % entre les centres parmi les 41 568 patients périopératoires et les grands malades. Les femmes étaient plus souvent transfusées (43,7 % vs 35,3 %,P < 0,0001), selon des taux plus élevés dans 8 centres sur 11. Comparées à celles d’un hôpital de référence choisi ayant un taux précis de transfusion près de la médiane, les probabilités de transfusion ajustées allaient de 0,44 à 1,53 globalement, de 0,42 à 1,22 chez les opérés à la hanche, de 0,72 à 3,17 chez les patients de cardiochirurgie et de 0,27 à 1,11 chez les grands malades et les polytraumatisés. Chez les 7 552 patients transfusés, la concentration minimale d’hémoglobine ajustée était de 74,0 ± 4,83 g·L-1 globalement et de 66,9 ± 1,7 g·L-1 à 84,5 ± 1,6 g·L-1 entre les centres. Des différences similaires ont été observées dans les centres parmi les patients avec fracture de la hanche (71,2 ± 2,9 g·L-1 à 82,8 ± 1,7 g·L-1), les patients de cardiochirurgie (65,7 ± 1,1 g·L-1 à 77,3 ± 1,0 g·L-1) et les grands malades et les polytraumatisés (66,1 ± 3,04 g·L-1 à 87,5 ± 2,5 g·L-1).ConclusionLes taux de transfusion de culots globulaires et les concentrations minimales d’hémoglobine diffèrent significativement en fonction de divers soins chirurgicaux et intensifs.

Low‐dose prophylactic platelet transfusions in recipients of an autologous peripheral blood progenitor cell transplant and patients with acute leukemia: a randomized controlled trial with a sequential Bayesian design

BACKGROUND:  Prophylactic platelet (PLT) transfusions are standard treatment for patients receiving high‐dose chemotherapy, but the optimal dose is not known. A randomized controlled trial was undertaken to examine the effectiveness of low‐dose PLT transfusions and to determine the need for further studies.