The prevalence of alloantibodies and ABO RhD blood groups in a cohort of Aboriginal and non-Aboriginal cardiac surgery patients from Australia.

INTRODUCTION: Limited evidence exists on the distribution of ABO RhD blood groups and prevalence and specificity of red blood cell (RBC) alloantibodies in Aboriginal and Torres Strait Islander peoples of Australia. We investigated RBC alloantibody prevalence and ABO RhD groups in Aboriginal patients undergoing cardiac surgery at a South Australian (SA) tertiary hospital, a major cardiac surgical referral centre for Northern Territory (NT) patients METHODS: Retrospective analysis of all consecutive patients undergoing cardiac surgery at Flinders Medical Centre (FMC) between January 2014 and June 2019. ABO and RhD blood groups, and RBC alloantibody prevalence, specificity, and clinical significance in Aboriginal and non-Aboriginal cardiac patients were determined at time of surgery and on follow up to 2021. RESULTS: 2327 patients were included, 588 (25.3 %) were from NT, and 420 (18.0 %) were Aboriginal. Aboriginal patients had a higher prevalence of ABO group O (59.8 % vs 43.9 %) and RhD positive (99.0 % vs 83.8 %). One-hundred-and-eleven patients had 154 RBC alloantibodies, 57/420 (13.6 %) Aboriginal versus 54/1907 (2.8 %) non-Aboriginal (p < 0.0001). There were higher numbers of IgM alloantibodies in Aboriginal patients (59/77, 76.6 %), with Lewis, P1 and M more common. Sixty patients had antibodies detected at time of surgery, 14 NT patients with previously detected alloantibodies, prior to surgery, presented with a negative antibody screen and 37 had new antibodies detected after cardiac surgery. CONCLUSION: A high prevalence of IgM alloantibodies was found in Aboriginal compared to non-Aboriginal cardiac surgery patients. The clinical significance of these IgM alloantibodies in Aboriginal peoples requires further investigation.

The complexities of transfusion reactions: Coexistence of a delayed haemolytic transfusion reaction and post-transfusion purpura.

BACKGROUND AND OBJECTIVES: Immune-mediated acute or delayed transfusion reactions occur when there is immunological incompatibility between transfused blood products and recipient's antibodies. Acute haemolytic transfusion reactions occur within 24 h and are delayed after 24 h up to 10 days following transfusion, whereas post-transfusion purpura (PTP) typically occurs 7-10 days post-transfusion. We present a case of a previously transfused and recently post-partum female who developed both delayed haemolytic transfusion reaction (DHTR) and PTP. CASE REPORT: A 42-year-old woman, G2P1, with non-alcoholic liver disease, portal hypertension and previous transfusion history with allogeneic anti-E, developed a severe DHTR and PTP following a complicated post-partum course and multiple transfusions. The antenatal and initial post-partum pre-transfusion antibody screens were negative. Subsequently five red cell antibodies, including anti-c, anti-Fya, anti-Jkb and anti-S and the reappearance of anti-E were, however, identified during follow-up investigations along with the anti-platelet antibody HPA-3a and human leukocyte antigen class I antibodies. Anti-E, anti-Jkb and anti-S were eluted from the circulating red blood cells. CONCLUSION: To our knowledge, there have been only two other case reports of DHTR and PTP occurring in the same patient.

Challenges in antibody titration for ABO-incompatible renal transplantation.

BACKGROUND AND OBJECTIVES: Accurate and regular monitoring of anti-A and anti-B titres pre- and post-transplantation plays a crucial role in the clinical management of patients receiving ABO-incompatible renal transplants. There is no standardized protocol or an external quality assurance program (EQA) currently available for this testing in Australia. The aim of this study was to investigate the diversity of techniques, test platforms and reagents that were currently in use in various laboratories with the aim of developing an EQA. MATERIALS AND METHODS: An online survey was sent to the participants enrolled with the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) to assess their interest in participation in the pilot study. A total of 24 participants who expressed interest were sent the group O plasma, A1 , A2 and B cells to perform ABO titration using their own methods. RESULTS: Participants reported a wide range of titre results, from 8 to 1024 for the anti-A titre using A1 cells, from 2 to 128 for anti-A titre using A2 cells and from neat to 32 for anti-B titre using B cells. CONCLUSION: There was a wide variation in titre results between and within different technologies. These findings demonstrate the need for an ABO titration EQA. Development of a standard technique and participation in an EQA program should, over time, reduce variation and enable transferrable results across testing centres, which will assist in consistent clinical interpretation and better outcomes for patients.

Extending the post-thaw viability of cryoprecipitate.

BACKGROUND: Cryoprecipitate has a short post-thaw expiry time of 6 h. The aim of this study was to assess the stability and function of cryoprecipitate components (FVIII, fibrinogen, vWF, and FXIII) and cryoprecipitate sterility up to 120 h post-thawing when stored at two temperatures (2-6°C and room temperature [20-24°C]). METHODS AND MATERIALS: Twenty batches (110 individual units) of time-expired, thawed cryoprecipitate were collected. Units were sampled at the 6-h expiration mark and then stored at 2-6°C or room temperature (RT). They were resampled every 24 h for 120 h. One unit from each batch was sent for sterility testing at 120 h. Samples had FVIII (one stage and chromogenic), fibrinogen, FXIII, vWFag, and vWF:RCo assays performed in batches. Rotational thromboelastometry (ROTEM) was also performed. RESULTS: FVIII levels declined significantly at 120 h post-thawing at both RT and 2-6°C, but still met international standards for FVIII content. Fibrinogen, vWF antigen, and FXIII levels reduced minimally over 120 h and always met international standard requirements when stored at either temperature. ROTEM analysis demonstrated that fibrinogen function was not compromised at 120 h post-thawing under both storage conditions. vWF:RCo levels declined significantly over 120 h at both storage temperatures. No bacterial contamination was detected in 20 units of cryoprecipitate following storage for 120 h post-thawing. CONCLUSION: These results demonstrate that extension of the storage time of thawed cryoprecipitate to 120 h, stored at either 2-6°C or RT, is feasible while still maintaining required FVIII, fibrinogen, and vWFag levels. Storage at 2-6°C has the advantage of reduced risk of potential bacterial contamination.

Anaemia in elderly patients at discharge from intensive care and hospital.

BACKGROUND AND OBJECTIVES: Anaemia is common in the elderly and is recognized as a risk factor for several adverse outcomes in older adults, including hospitalization, morbidity and mortality. The study aims were to examine the prevalence of anaemia in elderly patients at discharge from the intensive care unit (ICU) and hospital. MATERIALS AND METHODS: Patient randomized under the INFORM trial and with an ICU admission were included. Two cohorts, Cohort 1 patients who were alive on discharge from ICU and Cohort 2 patients who were discharged alive from hospital to home. Prevalence of significant anaemia defined as haemoglobin levels, less than 100 g/l was measured at ICU and hospital discharge. RESULTS: Overall, 76·5% (683/893) of elderly admissions in Cohort 1 had a haemoglobin <100 g/l, and 44·1% (395/893) had a haemoglobin <90 g/l on ICU discharge. Nadir haemoglobin during ICU stay, length of stay in ICU and transfusion during ICU stay was associated with significant anaemia at ICU discharge. At hospital discharge, in Cohort 2, 54·8% (263/480) of elderly ICU admissions had Hb < 100 g/l, and 23·4% (112/480) had Hb < 90 g/l. Male gender, haemoglobin level at ICU discharge, and length of stay and nadir Hb between ICU and hospital discharge were associated with anaemia at hospital discharge. CONCLUSIONS: Significant anaemia is highly prevalent in elderly patients on discharge from ICU and to a lesser degree at hospital discharge.

The burden of immune-mediated refractoriness to platelet transfusions in myelodysplastic syndromes.

Up to 65% of patients with myelodysplastic syndromes (MDS) have thrombocytopenia and require platelet (PLT) transfusion. The current standard of practice is to provide random- or single-donor PLT transfusion and manage PLT refractoriness (PLT-R) if and when it develops. This study assessed the prevalence and risk factors for immune-mediated PLT-R in patients in the South Australian (SA) MDS Registry. STUDY DESIGN AND METHODS: A retrospective analysis of MDS patients enrolled in the SA-MDS registry was performed. HLA data was analyzed from January 2003 to 30 June 2017 to ensure minimum follow-up of 2 years. RESULTS: During the study period, 341 of 681 (50%) MDS patients required at least one PLT transfusion, with 29 of 341 (9%) of all PLT transfusion patients requiring HLA-matched PLT transfusion for PLT-R. Of these 29 patients, 70% were females treated with disease-modifying therapies suggesting that these patients are at high risk of HLA alloimmunization. CONCLUSIONS: Immune-mediated PLT-R is common in MDS and can be expensive and difficult to manage once it occurs. Therefore, PLT transfusion practices should be optimized, especially for female MDS patients planned for disease-modifying therapies. This can help save time and streamline management, especially in the provision of PLT products for these patients, where the consequences of alloimmunization and PLT-R can be severe.

Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion.

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 .).

Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome.

Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support.

Any changes in recent massive transfusion practices in a tertiary level institution?

BACKGROUND & OBJECTIVES: A previous review of transfusion practices in our institution between 1998 and 2008 showed a trend of high ratios of red cells (RC) to plasma (FFP) and platelets to RC towards the later years of review period. The aim of the study was to further evaluate transfusion practices in the form of blood product usage and outcomes following massive transfusion (MT) METHODS: All adult patients with critical bleeding who received a MT (defined as ≥10 units of RC in 24h) in 2008 and between January 2010 and December 2014 were identified. Blood and blood products transfused, in-hospital mortality, 24h and 90-day mortality were analysed for the period 2010-2014. Blood and blood product usage, massive transfusion protocol (MTP) activation and use of ROTEM between 2008 and 2014 were compared. RESULTS: A total of 190 MT including surgical (52.1%), gastro-intestinal bleeding (25.3%), trauma (11.6%) and obstetric haemorrhage (5.8%) episodes were identified between 2010 and 2014. The overall in-hospital mortality was 26.7% with a significant difference in 24h (p=0.04) and 90-day mortality (p=0.02) between diagnostic groups. Comparing 2008 (n=33) and 2014 (n=23), there was no significant difference in median RC, FFP and platelet units, cryoprecipitate doses and RC:FFP ratio; however there was an increase in number of patients who used cryoprecipitate (54.5% vs 87%, p=0.01). CONCLUSION: Aligned with haemostatic resuscitation, the trend continues in the form of increased use of plasma and higher RC:FFP transfusion ratios including an increase in number of patients receiving cryoprecipitate.

Therapeutic plasma exchange does not reduce vasopressor requirement in severe acute liver failure: a retrospective case series.

BACKGROUND: In acute liver failure (ALF) therapeutic plasma exchange (TPE) improves laboratory measures of liver function. In patients with ALF requiring minimal vasoactive support TPE has also been shown to provide haemodynamic benefits including an increase in systemic blood pressure. However the haemodynamic effects of TPE in patients with severe ALF requiring moderate or high dose vasopressor therapy has not been reported. We retrospectively examined the haemodynamic effects of TPE in a cohort of patients with severe ALF requiring vasopressor therapy. METHODS: Physiological, laboratory and treatment data were collected on all patients with ALF who received TPE between January 2000 and December 2012. All patients were managed in the intensive care unit of a tertiary referral centre for ALF and liver transplantation. The primary outcome measures were changes in mean arterial pressure (MAP), vasopressor score and the ratio of vasopressor score to MAP (vasopressor dependency index (VDI)) from baseline prior to TPE through to 12 hours after completion of TPE. Secondary outcome measures were changes in other routinely collected physiological variables and laboratory results. Results are presented as median (interquartile range (IQR)). Outcome measures were evaluated using a mixed effect model. RESULTS: Thirty nine TPE were performed in 17 patients with ALF (13 paracetamol poisoning). All TPE were performed with a centrifugal apheresis system (duration 130 minutes (IQR 115 - 147.5), plasma volume removed 5.1% body weight (IQR 4.6 - 5.5). Baseline values for primary outcome measures were: MAP 82 mmHg (IQR 72 - 92.5), vasopressor score 8.35 (IQR 3.62 - 24.6) and VDI 0.10 (IQR 0.05 - 0.31). MAP was significantly higher immediately after TPE compared to baseline (p = 0.039), however when corrected for change in vasopressor requirement there was no significant change in VDI with TPE (p = 0.953). Twelve hours after TPE the MAP, vasopressor score and VDI were not significantly different from baseline (p = 0.563, p = 0.317 and p = 0.214 respectively). CONCLUSION: In this cohort of patients with severe ALF centrifugal TPE did not significantly affect vasopressor requirements.

A Retrospective Cohort Study of Red Cell Alloimmunisation in Rural, Remote, and Aboriginal and Torres Strait Islander Peoples Admitted to Intensive Care in the Northern Territory, Australia.

Red cell (RC) alloantibodies occur on exposure to non-self RC antigens in transfusion and pregnancy (typically IgG and clinically significant) or in association with non-RC immune environmental factors (typically IgM and not clinically significant). In Australia, the risk of RC alloimmunisation in First Nations peoples is unknown. We assessed the epidemiology, specificity, and antecedents of RC alloimmunisation via a data linkage retrospective cohort study of Northern Territory (NT) intensive care unit (ICU) patients (2015-2019). Of 4183 total patients, 50.9% were First Nations. In First Nations versus non-First Nations patients, the period prevalence of alloimmunisation was 10.9% versus 2.3%, with 390 versus 72 prevalent alloantibodies detected in 232 versus 48 alloimmunised patients, of which 135 (34.6%) versus 52 (72.2%) were clinically significant specificities. Baseline and follow-up alloantibody testing were available for 1367 patients, in whom new incident clinically significant alloantibodies developed in 4.5% First Nations versus 1.1% non-First Nations patients. On Cox proportional hazards modelling, adjusted hazard ratios (HR) showed First Nations status (HR 2.67 (95% CI 1.05-6.80), p = 0.04) and cumulative RC unit transfusion exposure (HR 1.03 (95% CI 1.01-1.05), p = 0.01) were independent predictors of clinically significant alloimmunisation. First Nations Australian patients are at increased risk of alloimmunisation due to RC transfusion, underscoring the importance of very judicious use of RC transfusions and shared decision-making with patients. Further studies are recommended to explore the role of other (non-RC) immune host factors, given the relative high prevalence of non-clinically significant IgM alloantibodies within alloimmunised First Nations patients.

Change in transfusion practice in massively bleeding patients.

This retrospective study evaluates changes in transfusion practice and modified blood product utilisation that occurred over the course of eleven years in patients receiving massive transfusion. The mean number of fresh frozen plasma units transfused increased from 9.0 ± 7.9 in 1998 to 11.3 ± 6.7 in 2008 (p=0.03). The mean number of platelet units increased from 1.9 ± 1.3 in 1998 to 2.6 ± 1.7 in 2008 (p=0.02). The proportion of cryoprecipitate increased from 0.03 ± 0.19 in 1998 to 1.3 ± 1.6 in 2008 (p=0.001). Along with these changes was a trend toward decreased mortality (p=0.05).

Red alert - a new perspective on patterns of blood use in the South Australian public sector.

OBJECTIVES: In 2006 South Australia had a red cell issue rate, measured as product issues per 1000 population, 22.4% higher than the national average. A pilot study was undertaken to investigate the disparity in issue rates between SA and the national average with a secondary aim of establishing information on SA red cell use. METHODS: A linked electronic database was developed using clinical, epidemiological and red cell transfusion data within hospitals in the SA public sector. Aggregated red cell use across the SA public health sector was analysed by clinical variables such as Diagnosis Related Group (DRG), including specialty related groups (SRGs) and major diagnostic categories (MDCs). The DRGs that were associated with blood use were identified and applied to national hospital separations data in order to derive comparative blood utilisation rates for SA and Australia. RESULTS: Although blood issue and usage by population measure showed a significant difference of 22.4 and 22.0% respectively between SA and Australia, when measured against weighted separations the differences reduced to 7.4 and 7.1% respectively. CONCLUSION: This study showed the importance of analysing blood issues and utilisation on an activity adjusted basis rather than a raw per capita basis.

Warming blood prior to transfusion using latent heat.

OBJECTIVE: Major trauma is associated with blood loss and hypothermia. It is common to replace lost fluid with red cells stored at 2-6°C, and/or colloid/crystalloid fluid stored at ambient temperature, thus increasing hypothermia risk. At trauma and medical retrieval sites, mains electricity powered fluid warmers cannot be generally used. Latent heat provides an alternate practical method of portable temperature-controlled intravenous fluid warming. This work investigates the safety and efficacy of a fluid warmer powered by latent heat. METHODS: Twenty-five haematology patients received red cell transfusions, one through a fluid warmer, using latent heat from a super-cooled liquid and one without warming. Temperature of donor red cell units was measured after passing through fluid warmers. Blood samples were collected from red cell units and patients, prior and after each transfusion. These were tested for haemolysis markers (plasma haemoglobin, potassium, lactate dehydrogenase, bilirubin) and for traces of super-cooled liquid. Patient physiological parameters (oxygen saturation, pulse, temperature, blood pressure, respiration) were monitored during each transfusion. RESULTS: Patient's physiological signs remained stable and no transfusion reactions were observed during warm transfusions. Latent heat fluid warmers increased the temperature of red cell units to approximately 35°C. There were no significant differences in haemolysis markers following warmed and unwarmed transfusions, and no contamination of red cell units by super-cooled liquid was detected. CONCLUSION: The latent heat fluid warmer was shown to safely warm transfused blood in a controlled clinical setting.

Can latent heat safely warm blood? - in vitro testing of a portable prototype blood warmer.

BACKGROUND: Trauma/retrieval patients are often in shock and hypothermic. Treatment of such patients usually involves restoring their blood volume with transfusion of blood (stored at 2 degrees C - 6 degrees C) and/or crystalloids or colloids (stored at ambient temperature). Rapid infusion of these cold fluids can worsen or even induce hypothermia in these patients. Warming of intravenous fluids at accident sites has traditionally been difficult due to a lack of suitable portable fluid warmers that are not dependent on mains electrical or battery power. If latent heat, the heat released when a liquid solidifies (an inherently temperature limiting process) can warm intravenous fluids, portable devices without a reliance on electrical energy could be used to reduce the incidence of hypothermia in trauma patients. METHODS: Rapid infusion of red cells into patients was timed to sample typical clinical flow rates. An approved dry heat blood warmer was compared with a prototype blood warmer using a supercooled liquid latent heat storage material, to warm red cells whilst monitoring inlet and outlet temperatures. To determine the effect of warming on red cell integrity compared to the normal storage lesion of blood, extracellular concentrations of potassium, lactate dehydrogenase and haemoglobin were measured in blood which had been warmed after storage at 2 degrees C - 6 degrees C for 1 to 42 days. RESULTS: A prototype latent heat fluid warmer consistently warmed red cells from approximately 4 degrees C to approximately 35 degrees C at typical clinical flow rates. Warming of stored blood with latent heat did not affect red cell integrity more than the approved dry heat blood warmer. CONCLUSION: Using latent heat as an energy source can satisfactorily warm cold blood or other intravenous fluids to near body temperature, without any adverse affects.

Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial.

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.

Rationale and Design of the Informing Fresh versus Old Red Cell Management (INFORM) Trial: An International Pragmatic Randomized Trial.

Although red blood cell transfusion is a potentially lifesaving intervention in severely anemic and acutely bleeding patients, some observational studies have suggested that prolonged red cell storage before transfusion is associated with harm. INFORM is a large, pragmatic, randomized controlled trial comparing the effect of the shorter storage with longer storage red blood cell transfusions on inhospital mortality in hospitalized patients who require a blood transfusion. The trial is being conducted in centers in Australia, Canada, Israel, and the United States and is expected to enroll 31497 patients. If the results of INFORM indicate that shorter storage red blood cell transfusion is associated with superior outcomes compared with standard issue red blood cell transfusion, consideration may be given to shortening blood storage times. If, in contrast, the INFORM trial provides no evidence of harm from longer storage red blood cells, clinicians and patients may be reassured that current blood inventory management strategies are appropriate.