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Summary 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.

Background Although observational studies suggest an association between transfusion of older red blood cell (RBC) units and increased postoperative risk, randomized trials have not supported this. The objective of this randomized trial was to test the effect of RBC storage age on outcomes after cardiac surgery. Methods From July 2007 to May 2016, 3835 adults undergoing coronary artery bypass grafting, cardiac valve procedures, or ascending aorta repair, either alone or in combination, were randomized to transfusion of RBCs stored for ≤14 days (younger units) or for ≥20 days (older units) intraoperatively and throughout the postoperative hospitalization. According to protocol, 2448 patients were excluded because they did not receive RBC transfusions. Among the remaining 1387 modified intent-to-treat patients, 701 were randomized to receive younger RBC units (median age, 11 days) and the remaining 686 to receive older units (median age, 25 days). The primary endpoint was composite morbidity and mortality, analyzed using a generalized estimating equation (GEE) model. The trial was discontinued midway owing to enrollment constraints. Results A total of 5470 RBC units were transfused, including 2783 in the younger RBC storage group and 2687 in the older RBC storage group. The GEE average relative-effect odds ratio was 0.77 (95% confidence interval [CI], 0.50-1.19; P = .083) for the composite morbidity and mortality endpoint. In-hospital mortality was lower for the younger RBC storage group (2.1% [n = 15] vs 3.4% [n = 23]), as was occurrence of other adverse events except for atrial fibrillation, although all CIs crossed 1.0. Conclusions This clinical trial, which was stopped at its midpoint owing to enrollment constraints, supports neither the efficacy nor the futility of transfusing either younger or older RBC units. The effects of transfusing RBCs after even more prolonged storage (35-42 days) remains untested.

Donor-derived T-cells mediate graft-versus-leukemia effect, immune reconstitution, and graft-versus-host-disease (GvHD) after allogeneic hematopoietic cell transplantation (HCT). We examined the association of donor cell subsets with outcomes in recipients of myeloablative allogeneic HCT using bone marrow (BM, N = 359) grafts from 2002 to 2014 with related or unrelated donors. Analysis considered pre-infusion graft total nucleated cell (TNC), CD34+ CD3+, CD4+, CD8+ doses. Most patients received busulfan-cyclophosphamide or etoposide-total body irradiation conditioning for acute leukemia or myelodysplastic syndrome. Calcineurin inhibitor-mycophenolate mofetil (CNI-MMF) (49%) or calcineurin inhibitor-methotrexate (CNI-MTX) (47%) were used for GvHD prophylaxis. In multivariable analysis, higher CD34+ dose was associated with platelet engraftment (P 0.001) and lymphocyte recovery (P = 0.006). There was no association of donor cell subsets with donor chimerism or overall survival. In conclusion, BM graft composition is associated with myeloablative allogeneic HCT outcomes and future studies to evaluate optimal graft composition are needed.

Objectives: Cold antibodies (CAs) are rarely significant for transfusion, but they can cause complications under the hypothermic conditions of cardiovascular surgery. The purpose of this study was to determine the incidence of such complications. Methods: Patients with CAs who underwent cardiovascular surgery were identified, and their records were reviewed for intraoperative complications attributable to CAs. Results: Over 14.5 years, of the 47,373 patients who underwent cardiovascular surgery, 99 had CAs before or within 30 days after surgery. Ninety-seven patients had hypothermic surgery, and intraoperative agglutination was noted in four; two of these cases were never reported to the transfusion service. Conclusions: The incidence of intraoperative complications among our patients with CAs was only 4%; therefore, the use of special testing protocols for the preoperative identification of CAs is neither necessary nor justified. Patient risk is best managed by preoperative clinical evaluation for potentially pathogenic CAs and intraoperative vigilance for agglutination.

Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008. Recursive partitioning analysis was used to identify Day 1 or Day 1+2 CD34+ collection quantity that predicted failure to reach target ≥ 2 × 10(6) CD34+ cells/kg within five days of collection. Totally, 172 patients were included in the analysis. Patients underwent mobilization with G-CSF or G-CSF+ chemotherapy. 23 of 172 patients (13.4%) failed to collect sufficient (≥ 2 × 10(6) CD34+ cells/kg) CD34+ cells after five days of apheresis: 22 of 29 who collected ≤ 0.70 × 10(6) CD34+ cells/kg and 1 of 143 who collected0.70 × 10(6) CD34+ cells/kg (75.9% vs. 0.7%, P0.001) on Day 1. Collection failure occurred in 23 of 30 patients who collected ≤ 1.54 × 10(6) CD34+ cells/kg and 0 of 142 who collected1.54 × 10(6) CD34+ cells/kg (76.7% vs. 0%, P0.001) on Days 1 + 2. Day 1 CD34+ cell collection quantity identifies patients unlikely to achieve adequate collection for ASCT. Patients who collect ≤ 0.70 × 10(6) CD34+ cells/kg on day 1 could be considered for treatment modifications to improve CD34+ collection, such as early administration of plerixafor or large volume apheresis.

Background Platelet transfusion has been reported to confer increased morbidity after cardiac surgery but prior studies were limited by confounding variables including red blood cell (RBC) transfusions. Our objective was to examine the impact of platelet transfusion on outcomes in cardiac surgery controlling perioperative risk factors. Methods A total of 32,298 patients underwent on-pump isolated coronary artery bypass grafting (CABG), an isolated valve, or a combined CABG and valve procedure between January 1, 1993 and January 1, 2006. Regression analysis and propensity methodology was employed to assess the association between platelet transfusion and morbidity. Results Univariate comparisons demonstrated that patients who received platelet transfusions had increased morbidity. After risk adjustment with both multivariable regression and propensity methods, platelet transfusion was not significantly associated with in-hospital mortality: odds ratio (OR) 0.74 confidence limits 0.58, 0.95, p = 0.017 and 2.05% vs 3.06%, p = 0.017, respectively. Among 2,774 propensity matched-pairs, platelet transfusion was associated with similar or reduced morbidity, platelets versus no platelets: cardiac 2.42% vs 1.77%, p = 0.09; pulmonary 8.94% vs 9.88%, p = 0.23; renal 1.33% vs 1.48%, p = 0.65; neurologic 2.27% vs 3.21%, p = 0.033; serious infection 4.15% vs 5.34%, p = 0.037; and composite outcome 15.0% vs 17.2%, p = 0.024. Among a propensity-matched subgroup of patients never administered a concomitant RBC transfusion, platelet transfusion was not associated with increased morbidity: 4.49% vs 2.99%, p = 0.31. Conclusions Platelet transfusion was not found to increase morbid risk after cardiac surgery. Our results should not be interpreted as advocating platelet transfusions in cardiac surgery; rather, platelet transfusion empirically in the setting of persistent microvascular bleeding is not associated with increased morbid risk.

Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) activity. A 53-year-old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use. The patient was treated with TPE until the pre-treatment ADAMTS13 activity was reported as normal without evidence of an inhibitor. TPE was stopped and the patient continued to improve without treatment. This patient's microangiopathic hemolytic anemia (MAHA) appeared to be secondary to cocaine use. The proposed pathogenesis is likely a combination of cocaine-induced vasoconstriction, vascular damage, platelet activation, and procoagulation. This is the fifth published report of cocaine-induced MAHA and to our knowledge the first with ADAMTS13 testing.

We sought to determine whether patients requiring more aphereses to obtain adequate numbers of CD34+ cells had delayed hematopoietic recovery following autologous transplantation. We identified 496 consecutive individuals with lymphoma who underwent hematopoietic stem cell mobilization using etoposide and G-CSF and first autologous transplantation. In multivariate analysis, increased apheresis days as a continuous and as a categorical variable at ⩾5/

Perioperative vasoplegia is associated with increased morbidity. Red blood cell (RBC) transfusion increases plasma concentrations of inflammatory mediators, possibly contributing to the development of vasoplegia. We investigated the prevalence of mild and profound postoperative vasoplegia, identified factors associated with its development, and examined the role of RBC and component transfusion on the occurrence of postoperative vasoplegia.Between January 1, 2000, and January 1, 2007, 25,960 patients underwent on-bypass cardiac surgical procedures. The incidence of vasoplegia was defined as (1) mild vasoplegia requiring norepinephrine infusion for blood pressure support on the day of operation and postoperative day 1, and (2) profound vasoplegia requiring vasopressin, with or without concomitant norepinephrine infusion, on the day of operation and postoperative day 1. Separate logistic regression models were used to model risk factors for development of mild and profound vasoplegia.RBC transfusion increased risk-adjusted odd ratios (ORs) of developing mild vasoplegia (1.07 [95% confidence limits (CL), 1.05, 1.10]; p0.001) and profound vasoplegia (1.38 [1.31, 1.46] p0.001). The risk-adjusted ORs (95% CL) for mild vasoplegia and profound vasoplegia were similarly increased by fresh-frozen plasma (OR, 1.24 [1.10, 1.41], p0.001; and OR, 1.20 [1.13, 1.29], p0.001) and platelet transfusion (OR, 1.39 [1.25, 1.54], p0.001; and OR, 1.22 [1.14, 1.31], p0.001), respectively.Red blood cells, fresh-frozen plasma, and platelet transfusion increased the prevalence of vasoplegia. RBC transfusion exhibited a dose-dependent response for developing vasoplegia with each RBC unit transfused. Further investigation is necessary to determine whether prophylactic use of vasopressor support in the setting of transfusion can ameliorate risk and effect outcomes.

Conventional pretransfusion testing uses hemagglutination to ensure donor-recipient compatibility for ABO/D status and recipient alloantibodies. While screening large numbers of donor units for multiple antigens by hemagglutination is impractical, novel methods of DNA analysis permit the rapid determination of an extended human erythrocyte antigen (xHEA) phenotype. A prospective observational study was conducted at four hospital transfusion services to test an alternative paradigm of identifying xHEA-typed units for patients in three cohorts by utilizing DNA analysis and a novel inventory management model.xHEA typing of recipient samples and donor units of known ABO/D status was performed by HEA analysis (BeadChip, BioArray Solutions). xHEA-typed units were assigned to pending transfusion requests using an inventory management system designed to simulate blood order processing. The fraction of requests fulfilled, or "fill fraction" (FF) was determined at four levels of matching stringency.For alloimmunized patients, all but one participating site observed an FF of more than 95% when matching for ABO, D, and known alloantibodies and an FF of more than 90% when additionally matching for C, c, E, e, and K; the site handling the most challenging requests still observed FFs of 62 and 51%, respectively. FF was found to correlate positively with the ratio of available donor units to units requested and negatively with the degree of recipient alloimmunization.This study demonstrates that substantial fill fractions can be achieved by selecting existing donor units for xHEA analysis and operating an inventory management system for efficient allocation of units to recipients.

True lung injury is among the leading causes of transfusion-related mortality. Pulmonary morbidity after cardiac surgery has been related to damaging effects of cardiopulmonary bypass and transfusion, but is confounded by cardiac-related events that may not reflect true lung injury. Thus, cardiac surgery poses unique challenges to criteria-specific diagnosis of transfusion-related acute lung injury (TRALI). Our objective was to determine the prevalence of pulmonary morbidity related to transfusion and whether TRALI consensus-criteria are applicable to cardiac surgery.A total of 16,847 patients underwent on-pump, coronary artery bypass grafting (CABG), valve, or CABG-valve surgery from September 1998 to February 1, 2006. We performed four propensity-score-matching analyses with logistic regression on probability of receiving a transfusion: total hospital red blood cell (RBC) and fresh frozen plasma (FFP) transfusion and intraoperative RBC and FFP transfusion. Outcomes included traditional cardiac-surgery-defined pulmonary morbidity and ratio of arterial partial pressure of oxygen to fractional inspired oxygen concentration (PaO(2)/FiO(2)), a criterion for TRALI.Patients receiving RBC transfusion had more risk-adjusted pulmonary complications: respiratory distress 4.8% vs 1.5%, p0.001; respiratory failure 2.2% vs 0.39%, p0.0001; longer intubation times, 9.9 hours vs 7.5 hours, p0.0001; acute respiratory distress syndrome, 0.64% vs 0.21%, p = 0.015; and reintubation, 5.6% vs 1.3%, p0.0001. The FFP was similarly related to more pulmonary complications after surgery. By TRALI criteria, the majority manifested "lung injury" (PaO(2)/FiO(2) ratio300) but unrelated to transfusion (65% vs 64%).Transfusion is associated with many measures of postoperative pulmonary morbidity. Yet the PaO(2)/FiO(2) ratio as important criterion of TRALI is unrelated to transfusion. Thus, due to the nature of cardiac surgery, application of consensus guided diagnosis of TRALI is problematic.