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Concept: Transfusion reaction

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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 .).

Concepts: Red blood cell, Hematology, Blood transfusion, Transfusion reaction, Informed consent, Blood, Blood bank

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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 .).

Concepts: Illness, Epidemiology, Transfusion reaction, Medical statistics, Red blood cell, Blood, Blood type, Blood transfusion

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Patients with cancer are often dependent on blood transfusions during treatment. Frequent vital sign monitoring during transfusions may interrupt sleep and the patient’s ability to ambulate or participate in unit activities. Relying heavily on vital sign findings may also overshadow unmeasurable symptoms of transfusion reaction. The aim of this evidence-based practice initiative was to examine the evidence regarding the optimum frequency of vital sign monitoring for patients undergoing stem cell transplantation receiving blood products and to amend policy and practice to be consistent with the literature. 
At a Glance
Patients with cancer frequently require transfusion support during treatment.Inconsistencies exist in recommendations for the frequency of vital sign monitoring during transfusion.Examining best practice guidelines suggests that less frequent vital sign monitoring may be appropriate if coupled with thoughtful physiologic assessment.

Concepts: Red blood cell, Cross-matching, AIDS, Hematology, Transfusion medicine, Chemotherapy, Transfusion reaction, Blood transfusion

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Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model.

Concepts: Hemoglobin, Transfusion reaction, Blood transfusion, Hemolytic anemia, Blood, Hematology, Disseminated intravascular coagulation, Red blood cell

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A blood cross-matching test should be carried out to prevent a hemolytic transfusion reaction as the final verification step. To simplify complicated procedures of a conventional blood cross-matching test requiring bulky systems and skilled people, we present a finger-actuated microfluidic device for the blood cross-matching test. Although finger actuation is a simple action that anyone can easily accomplish, there would be a variation in the individual finger actuation that may induce the user-dependent errors of the device. Therefore, the working principle of the finger-actuated microfluidic device is newly designed to reduce the user-dependent errors by indirectly controlling the pressure of fluidic channels. The constant volume was repeatedly dispensed by pushing and releasing a pressure chamber regardless of the different pushed depths of the pressure chamber, the pushing time interval, and the end-users. The dispensed volume was linearly increased according to the number of pushing times applied to the pressure chamber and determined by adjusting the diameter of an actuation chamber. In addition, multiple fluids can be dispensed with a desirable ratio by pushing and releasing the pressure chamber. Finally, a finger-actuated microfluidic device for the blood cross-matching test was developed, which can simultaneously actuate four fluidic channels. After loading 50 μL of whole blood samples from a donor and a recipient into two inlets of the device, the blood plasma from each individual was separated through the two plasma separation membranes. The blood cross-matching test results can be achieved by cross-reacting the donor’s blood plasma with the recipient’s whole blood as well as the donor’s whole blood with the recipient’s blood plasma by pushing and releasing only a single pressure chamber within 10 min.

Concepts: Microfluidics, Blood donation, Blood type, Cross-matching, Blood, Hematology, Transfusion reaction, Blood transfusion

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Here, we report the biochemical and genetic basis of the Vel blood group antigen, which has been a vexing mystery for decades, especially as anti-Vel regularly causes severe hemolytic transfusion reactions. The protein carrying the Vel blood group antigen was biochemically purified from red blood cell membranes. Mass spectrometry-based de novo peptide sequencing identified this protein to be small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. Expression of SMIM1 cDNA in Vel- cultured cells generated anti-Vel cell surface reactivity, confirming that SMIM1 encoded the Vel blood group antigen. A cohort of 70 Vel- individuals was found to be uniformly homozygous for a 17 nucleotide deletion in the coding sequence of SMIM1. The genetic homogeneity of the Vel- blood type, likely having a common origin, facilitated the development of two highly specific DNA-based tests for rapid Vel genotyping, which can be easily integrated into blood group genotyping platforms. These results answer a 60 year-old riddle and provide tools of immediate assistance to all clinicians involved in the care of Vel- patients.

Concepts: Protein, Genetics, Blood, Blood type, Transfusion reaction, DNA, Gene, Red blood cell

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Blood transfusions are critically important in many medical procedures but the presence of antigens on red blood cells (RBCs, erythrocytes) means that careful blood-typing must be carried out prior to transfusion to avoid adverse and sometimes fatal reactions following transfusion. Enzymatic removal of the terminal N-acetylgalactosamine or galactose of A- or B- antigens, respectively, yields universal O-type blood, but is inefficient. Starting with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A- and B-antigens from some of the linkages on RBC surface glycans, through several rounds of evolution, we developed variants with vastly improved activity towards some of the linkages that are resistant to cleavage by the wild-type enzyme. The resulting enzyme effects more complete removal of blood group antigens from cell surfaces, demonstrating the potential for engineering enzymes to generate antigen-null blood from donors of various types.

Concepts: Malaria, Transfusion reaction, Blood type, Blood transfusion, ABO blood group system, Hematology, Blood, Red blood cell

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Anemia is frequent among brain-injured patients, where it has been associated with an increased risk of poor outcome. The pathophysiology of anemia in this patient population remains multifactorial; moreover, whether anemia merely reflects a higher severity of the underlying disease or is a significant determinant of the neurological recovery of such patients remains unclear. Interestingly, the effects of red blood cell transfusions (RBCT) in moderately anemic patients remain controversial; although hemoglobin levels are increased, different studies observed only a modest and inconsistent improvement in cerebral oxygenation after RBCT and raised serious concerns about the risk of increased complications. Thus, considering this “blood transfusion anemia paradox”, the optimal hemoglobin level to trigger RBCT in brain-injured patients has not been defined yet; also, there is insufficient evidence to provide strong recommendations regarding which hemoglobin level to target and which associated transfusion strategy (restrictive versus liberal) to select in this patient population. We summarize in this review article the more relevant studies evaluating the effects of anemia and RBCT in patients with an acute neurological condition; also, we propose some potential strategies to optimize transfusion management in such patients.

Concepts: Transfusion reaction, Bone marrow, Anemia, Blood, Blood transfusion, Hematology, Hemoglobin, Red blood cell