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Numerous retrospective clinical studies suggest that transfusion of longer stored red blood cells (RBCs) is associated with an independent risk of poorer outcomes for certain groups of patients, including trauma, intensive care, and cardiac surgery patients. Large multicenter randomized controlled trials are currently underway to address the concern about RBC storage duration. However, none of these randomized controlled trials focus specifically on trauma patients with hemorrhage. Major trauma, particularly due to road accidents, is the leading cause of critical injury in the younger-than-40-year-old age group. Severe bleeding associated with major trauma induces hemodynamic dysregulation that increases the risk of hypoxia, coagulopathy, and potentially multiorgan failure, which can be fatal. In major trauma, a multitude of stress-associated changes occur to the patient's RBCs, including morphological changes that increase cell rigidity and thereby alter blood flow hemodynamics, particularly in the microvascular vessels, and reduce RBC survival. Initial inflammatory responses induce deleterious cellular interactions, including endothelial activation, RBC adhesion, and erythrophagocytosis that are quickly followed by profound immunosuppressive responses. Stored RBCs exhibit similar biophysical characteristics to those of trauma-stressed RBCs. Whether transfusion of RBCs that exhibit storage lesion changes exacerbates the hemodynamic perturbations already active in the trauma patient is not known. This article reviews findings from several recent nonrandomized studies examining RBC storage duration and clinical outcomes in trauma patients. The rationale for further research on RBC storage duration in the trauma setting is provided. [ABSTRACT FROM AUTHOR]

[Display omitted] • Storage-related changes were identified in Red Cell Concentrate using SORS. • MuSCA was employed to assess Raman data against parallel bioanalytical measurements. • Spectral markers strongly correlated with respective bioassays in RCC were revealed. • Our approach enabled direct quality monitoring of RCC within sealed transfusion bags. In this work we employ Spatially Offset Raman Spectroscopy (SORS) to non-invasively identify storage-related changes in red blood cell concentrate (RCC) in-situ within standard plastic transfusion bags. To validate the measurements, we set up a parallel study comparing both bioanalytical data (obtained by blood-gas analysis, hematology analysis and spectrophotometric assays), and Raman spectrometry data from the same blood samples. We then employ Multisource Correlation Analysis (MuSCA) to correlate the different types of data in RCC. Our analysis confirmed a strong correlation of glucose, methemoglobin and oxyhemoglobin with their respective bioassay values in RCC units. Finally, by combining MuSCA with k -means clustering, we assessed changes in all Raman wavenumbers during cold storage in both RCC Raman data from the current study and parallel RCC supernatant Raman data previously acquired from the same units. Direct RCC quality monitoring during storage, would help to establish a basis for improved inventory management of blood products in blood banks and hospitals based on analytical data. [ABSTRACT FROM AUTHOR]

Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the “RBC storage lesion.” There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage time and varies markedly between individuals. Oxidative damage is considered a significant factor in the development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG,2H + /2GSH couple ( E hc ), and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52±0.63 mM (median ± SD) and 0.032±0.107 mM, respectively, over 42 days). Taking into account the decline in pH, E hc became more positive (oxidized) during storage (median net increase of 35±16 mV). In our study population heritability estimates for GSH, GSSG, tGSH, and E hc measured over 56 days of storage are 79, 60, 67, and, 75%, respectively. We conclude that susceptibility of stored RBCs to oxidative injury due to variations in the GSH redox buffer is highly variable among individual donors and strongly heritable. Identifying the genes that regulate the storage-related changes in this redox buffer could lead to the development of new methods to minimize the RBC storage lesion. [ABSTRACT FROM AUTHOR]

Stored blood components are a critical life-saving tool provided to patients by health services worldwide. Red cells may be stored for up to 42 days, allowing for efficient blood bank inventory management, but with prolonged storage comes an unwanted side-effect known as the "storage lesion", which has been implicated in poorer patient outcomes. This lesion is comprised of a number of processes that are inter-dependent. Metabolic changes include a reduction in glycolysis and ATP production after the first week of storage. This leads to an accumulation of lactate and drop in pH. Longer term damage may be done by the consequent reduction in anti-oxidant enzymes, which contributes to protein and lipid oxidation via reactive oxygen species. The oxidative damage to the cytoskeleton and membrane is involved in increased vesiculation and loss of cation gradients across the membrane. The irreversible damage caused by extensive membrane loss via vesiculation alongside dehydration is likely to result in immediate splenic sequestration of these dense, spherocytic cells. Although often overlooked in the literature, the loss of the cation gradient in stored cells will be considered in more depth in this review as well as the possible effects it may have on other elements of the storage lesion. It has now become clear that blood donors can exhibit quite large variations in the properties of their red cells, including microvesicle production and the rate of cation leak. The implications for the quality of stored red cells from such donors is discussed. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of leukoreduction (LR) as compared to standard nonleukoreduced (NLR) units on cytokine concentrations in canine erythrocyte concentrates during regular storage time. Design Randomized, experimental study. Setting University teaching hospital. Animals Ten random-source research dogs. Interventions One unit of whole blood was collected from each dog and randomized to standard processing (NLR, n = 5) or prestorage LR ( n = 5). All units were stored at 4°C. Samples were aseptically collected from each unit weekly for 5 weeks. On day 35, 1 mL of blood was collected from each unit and submitted for aerobic culture. Measurement and Main Results An ELISA assay was used to analyze the concentrations of IL-1β, IL-8, TNF-α, and IL-10. There were no significant effects of either group or storage time for IL-1β, IL-10, or TNF-α. IL-8 concentration was significantly increased over the storage period in NLR units, and was significantly higher compared to LR units on days 28 and 35. Aerobic culture was negative on all units. Conclusions This study demonstrated a marked, storage time-dependent accumulation of IL-8 in canine erythrocyte concentrates. Prestorage LR attenuated the accumulation of IL-8. This chemokine may contribute to the proinflammatory effects of transfusion of stored erythrocyte concentrates. [ABSTRACT FROM AUTHOR]

Background and Objectives If transfusion of older stored red cells is found to negatively affect clinical outcome, one possible alternative to shortened outdate is the use of new additive solutions ( AS) that ameliorate the storage lesion. Erythro- Sol ( E- Sol), a previously developed next-generation AS, has been reformulated into E- Sol 5, which is compatible with current anticoagulants and AS volumes. The effect of E- Sol 5 on red cells during storage compared to current AS has not been reported. Materials and Methods Paired, ABO-matched whole-blood units were collected into CPD anticoagulant, pooled, split and processed into plasma and red cell units with either 110 ml of Adsol or 105 ml of E- Sol 5 within 8 h of collection. In Study 1, paired units in E- Sol 5 and Adsol were sampled on Day 0 and every 7 days up to Day 42 ( n = 10). In Study 2, paired units in E- Sol 5 and Adsol were sampled only on Day 0 and Day 42 ( n = 10). Results In Study 1, 2,3 DPG levels were maintained until Day 28 in E- Sol 5 units and Day 14 in Adsol units. ATP levels were higher in E- Sol 5 units until Day 21, after which they were comparable between the two groups. In both studies, metabolic activity was greater in E- Sol 5 units with respect to glucose consumption and lactate production. Morphology scores were higher, and haemolysis and microparticles generated were lower in E- Sol 5 vs. Adsol units. Weekly mixing of units lowered haemolysis and microparticle levels and increased potassium content on Day 42 in both additive solutions. Conclusion Regardless of whether units are mixed weekly or are stored non-mixed, E- Sol 5 slows the progression of the red cell storage lesion and improves the overall in vitro quality of RBC throughout storage. [ABSTRACT FROM AUTHOR]

Objectives To discuss and review blood transfusion practices in dogs and cats including collection and storage of blood and administration of products. To report new developments, controversial practices, less conventional blood product administration techniques and where applicable, describe the relevance to anaesthetists and anaesthesia. Databases used PubMed and Google Scholar using dog, cat, blood transfusion, packed red blood cells and whole blood as keywords. Conclusions Blood transfusions improve oxygen carrying capacity and the clinical signs of anaemia. However there are numerous potential risks and complications possible with transfusions, which may outweigh their benefits. Storage of blood products has improved considerably over time but whilst extended storage times may improve their availability, a phenomenon known as the storage lesion has been identified which affects erythrocyte viability and survival. Leukoreduction involves removing leukocytes and platelets thereby preventing their release of cytokines and bioactive compounds which also contribute to storage lesions and certain transfusion reactions. Newer transfusion techniques are being explored such as cell salvage in surgical patients and subsequent autologous transfusion. Xenotransfusions, using blood and blood products between different species, provide an alternative to conventional blood products. [ABSTRACT FROM AUTHOR]

Background The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. Materials and methods Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell ( PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep ( n = 12) was transfused with two units of ovine PRBC. Results Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline-adenine-glucose-mannitol ( SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. Conclusion These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions. [ABSTRACT FROM AUTHOR]

Background: The transfusion of packed red blood cells (PRBC) is associated with various side effects, including storage damage to PRBCs. The cells change their structure, releasing potassium as well as lactate. Mechanical rinsing, available in many hospitals, is able to remove toxic substances and possibly minimizes the negative side effects of transfusion., Objective: The primary aim of our study was to improve the quality of PRBCs before transfusion. The effects of different washing solutions on PRBC quality were analyzed., Material and Methods: This in vitro study compares 30 mechanically washed PRBCs. They were either processed with standard normal saline 0.9% (n = 15, N group) or a hemofiltration solution containing 4 mmol/l potassium (n = 15, HF group) by a mechanical rinsing device (Xtra, LivaNova, Munich, Germany). A subgroup analysis was performed based on the storage duration of the processed PRBCs (7, 14, 37 days). Samples were taken before washing (EKprä), immediately after washing (EKpost) and 10 h later (EKpost10h), after storage in the "wash medium" at room temperature. Concentrations of ATP (probability of survival in transfused erythrocytes), lactate, citrate and electrolytes (potassium, sodium, chloride, calcium) were tested., Results and Conclusion: Mechanical rinsing improves pretransfusion quality of PRBC. Washing with a hemofiltration solution results in a more physiological electrolyte composition. Even 10 h after mechanical rinsing with a hemofiltration solution, the quality of 37-day-old PRBC is comparable to young PRBC that have been stored for 7 days and have not been washed. Washing stored PRBC increases the ATP content, which subsequently leads to an increased probability of survival of red cells after transfusion., (© 2022. The Author(s).)

The past two decades have witnessed increased scrutiny regarding efficacy and risk of the once unquestioned therapy of red blood cell (RBC) transfusion. Simultaneously, a variety of changes have been identified within the RBC and storage media during RBC preservation that are correlated with reduced tissue oxygenation and transfusion-associated adverse effects. These alterations are collectively termed the storage lesion and include extensive biochemical, biomechanical, and immunologic changes involving cells of diverse origin. Time-dependent falls is 2,3-diphosphoglycerate, intracellular RBC adenosine triphosphate, and nitric oxide have been shown to impact RBC deformability and delivery of oxygen to the end-organ. The accumulation of biologic response modifiers such as soluble CD40 ligand (sCD40L), lysophosphatidylcholine (lyso-PC), and Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) have been associated with altered recipient immune function as well. This review will address the alterations occurring within the RBC and storage media during RBC preservation and will address the potential clinical consequence thereof.

Irradiation of cellular blood components is well established as a countermeasure against transfusion-associated graft-versus-host disease (TA-GVHD). Unintended consequences of ionizing radiation are also well established. The red cell "storage lesion" – a progression of metabolic, functional, and morphological changes – may be exacerbated by irradiation rates and doses typically used for TA-GVHD prophylaxis. With or without irradiation, a storage lesion change of clinical concern is the accelerated egress of intracellular potassium. ATP depletion during storage limits the activity of the red cell membrane's sodium-potassium pump (Na,K-ATPase), which normally maintains intracellular potassium (K+) at levels 30–40 times higher than the extracellular milieu. The natural diffusion of potassium down this concentration gradient proceeds faster if the cell membrane is damaged, and oxidative damage to cellular membranes and membrane proteins – including Na,K-ATPase – is an effect of ionizing radiation. Preventing transfusion-related hyperkalemia is a reason for limiting the shelf life of irradiated red cells. In the absence of specific measurements to assess storage lesion in a particular unit of blood, and in the absence of specific interventions at the time of transfusion to mitigate effects of storage lesion, it is consistent with the precautionary principle to put conservative limits on a blood component's shelf life. On the other hand, both the safety and sufficiency of a nation's blood supply might be improved by interventions that benefit specific recipients when they are transfused, and benefit future patients by extending the allowable shelf life of blood components. Potassium filtration of irradiated red blood cell components is one such intervention. [ABSTRACT FROM AUTHOR]

From the perspectives of disease transmission and sterility maintenance, the world's blood supplies are generally safe. However, in multiple clinical settings, red blood cell (RBC) transfusions are associated with adverse cardiovascular events and multiorgan injury. Because ~85 million units of blood are administered worldwide each year, transfusion-related morbidity and mortality is a major public health concern. Blood undergoes multiple biochemical changes during storage, but the relevance of these changes to unfavorable outcomes is unclear. Banked blood shows reduced levels of S-nitrosohemoglobin (SNO-Hb), which in turn impairs the ability of stored RBCs to effect hypoxic vasodilation. We therefore reasoned that transfusion of SNO-Hb-deficient blood may exacerbate, rather than correct, impairments in tissue oxygenation, and that restoration of SNO-Hb levels would improve transfusion efficacy. Notably in mice, administration of banked RBCs decreased skeletal muscle pO2, but infusion of renitrosylated cells maintained tissue oxygenation. In rats, hemorrhage-induced reductions in muscle pO2 were corrected by SNO-Hb-repleted RBCs, but not by control, stored RBCs. In anemic awake sheep, stored renitrosylated, but not control RBCs, produced sustained improvements in O2 delivery; in anesthetized sheep, decrements in hemodynamic status, renal blood flow, and kidney function incurred following transfusion of banked blood were also prevented by renitrosylation. Collectively, our findings lend support to the idea that transfusions may be causally linked to ischemic events and suggest a simple approach to prevention (i.e., SNO-Hb repletion). If these data are replicated in clinical trials, renitrosylation therapy could have significant therapeutic impact on the care of millions of patients. [ABSTRACT FROM AUTHOR]

Background and Objectives Glucose and acetate have been proposed to be required elements in platelet storage media. This study investigated the role of these compounds on the varied elements that comprise the platelet storage lesion. Materials and Methods For each replicate, four pooled and split ABO group-specific buffy coat-derived platelet concentrates were suspended in an in-house additive solution with minimal plasma and varying final concentrations of acetate or glucose. Units were sampled on days 2, 3, 6, 8 and 10 and tested for markers of platelet morphology, activation, function, metabolism and indicators of cell death. Results The absence of glucose was associated with a decrease in ATP, falling to a mean of 1·1 ± 0·1 μmol/1011 plts in units with no added glucose compared with 4·2 ± 0·6 μmol/1011 plts ( P < 0·001) in units with 30 m m glucose. As glucose became depleted, the decrease in ATP to levels below 3 μmol/1011 plts was associated with an increase in both annexin V binding and intracellular free calcium. In units lacking exogenous acetate, ATP levels on day 10 were 5·2 ± 1·5 μmol/1011 plts compared with 2·7 ± 0·9 μmol/1011 plts in units with 56 m m acetate ( P = 0·006). Higher concentrations of exogenous acetate were associated with a lower hypotonic shock response and higher surface expression of CD62P suggestive of a dose dependency. Conclusion Under current physical storage conditions, glucose appears necessary for the maintenance of platelets stored as concentrates in minimal volumes of plasma. The addition of acetate was associated with increased platelet activation and reduced ATP levels. [ABSTRACT FROM AUTHOR]

Background Changes that occur to red blood cells ( RBCs) during routine blood bank storage include decreased deformability, increased haemolysis and oxidative damage. Oxidative injury to the RBC membrane and haemoglobin can affect changes in shape and deformability. Ascorbic acid ( AA) is an antioxidant that maintains haemoglobin in a reduced state and minimises RBC oxidative injury. We hypothesised that AA would improve membrane fragility and decrease haemolysis during storage. Methods Whole blood derived, AS-5 preserved, pre-storage leucoreduced RBC units were exposed to either AA or saline control solutions. Several rheological and biochemical parameters were measured serially during storage, including RBC membrane mechanical fragility, percent haemolysis and methaemoglobin levels. Results AA exposure significantly reduced mechanical fragility and haemolysis over the entire storage period. The highest two concentrations of AA affected the greatest reductions in mechanical fragility and percent haemolysis. Addition of AA to the RBCs did not significantly alter their biochemical parameters compared to control RBCs incubated with saline. Conclusion AA reduced RBC membrane fragility and decreased haemolysis during storage without adversely affecting other RBC biochemical parameters. The clinical significance of these findings needs to be determined. [ABSTRACT FROM AUTHOR]

Abstract: The introduction of pre-storage leukoreduction in the preparation of standard RBCs intended for transfusion provided significant improvement in the quality of labile products and their post transfusion viability and effects, although the literature data are controversial. To elucidate the issue of the probable leukoreduction effects on RBCs storage lesion, we evaluated various storage quality measures in RBCs stored in either leukoreduced (L) or non-leukoreduced (N) units, with emphasis to senescence and oxidative stress associated modifications. Our data suggest that the residual leukocytes/platelets of the labile products represent a stressful storage factor, countering the structural and functional integrity of stored RBCs. Hemolysis, irreversible echinocytosis, microvesiculation, removal signaling, ROS/calcium accumulation, band 3-related senescence modifications, membrane proteome stress biomarkers as well as emergence of a senescence phenotype in young RBCs that is disproportionate to their age, are all encountered more or mostly in N-RBCs compared to the L-RBCs, either for a part or for the whole of the storage period. The partial, yet significant, alleviation of so many storage-related manifestations in the L-RBCs compared to the N-RBCs, is presented for the first time and provides a rational mechanistic interpretation of the improved storage quality and transfusions observed by the introduction of pre-storage leukoreduction. This article is part of a Special Issue entitled: Integrated omics. [Copyright &y& Elsevier]

Background: Storage duration of red cells has been associated with increased morbidity and mortality following transfusion. This association has been attributed to the loss of deformability of stored red cells leading to deterioration of microvascular perfusion. ATP content is considered a critical determinant of the deformability of stored red cells. Methods: ATP content and deformability were determined after storage for up to 49 days in 40 leukocyte-depleted whole blood units. Red cell deformability was determined using a laser-assisted optical rotational cell analyzer (LORCA®) employing shear stress (SS) ranging from 0.3 to 30 Pa. Deformability was expressed as the elongation index (EI). EI was correlated with ATP content. Results: ATP content decreased from 3.5 to 1.7 mmol/g hemoglobin. EI increased from 0.03 to 0.05 at an SS of 0.3 Pa, and decreased from 0.62 to 0.59 at an SS of 30 Pa. Correlation coefficient (r) of ATP vs. EI at 0.3 Pa ranged from -0.17 to +0.15 during storage. At 30 Pa, r ranged from -0.03 to +0.45. Correlation increased with storage irrespective of SS, and increased with SS irrespective of storage. Conclusions: ATP content is not a valid surrogate marker for red cell deformability and may not reflect in vivo survival of stored red cells. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Perioperative blood transfusion has been linked to decreased survival in pancreatic cancer; however, the exact causal mechanism has not been elucidated. Allogeneic transfusions are known to expose patients to foreign cells and lipid mediators. We hypothesize that stored packed red cells (pRBCs) contain pro-cancer cytokines that augment tumor progression. We analyzed the plasma fraction of stored pRBCs for pro-cancer cytokines and evaluated the affect of both storage time and leukocyte reduction on these mediators. Methods: Chemiarray™ analysis for pro-cancer cytokines was performed on the acellular plasma fraction of stored leukocyte-reduced (LR) and non-leukocyte-reduced (NLR) pRBCs at day 1 (D.1-fresh) and day 42 (D.42-outdate) of storage. Elevated expression of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), angiogenin, tumor necrosis factor-alpha (TNF-α), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) was found. Specific enzyme-linked immunosorbent assay was performed for each of these factors in LR and NLR blood at D.1, day 28, and D.42. Data were analyzed by ANOVA. A p value ≤0.05 was considered significant; N ≥ 4 per group. Migration assays were performed using inhibitors of EGF (gefitinib) and PDGF (imatinib) on murine pancreatic adenocarcinoma cells (Pan02) exposed to D.1 and D.42 LR and NLR plasma. Proliferation assays were performed on Pan02 cells to test the inhibition of PDGF. Results: MCP-1 levels increased with storage time in LR blood, 86.3 ± 6.3 pg/ml at D.1 vs. 121.2 ± 6.1 pg/ml at D.42 ( p = 0.007), and NLR blood, 78.2 ± 7.3 pg/ml at D.1 vs. 647.8 ± 220.7 pg/ml at D.42 ( p = 0.02). RANTES levels are lower in LR compared to NLR stored blood, 3.0 ± 1.9 vs. 15.8 ± 0.7 pg/ml at D.42 ( p < 0.001), but similar in D.1 blood, 13.8 ± 1.8 pg/ml in LR vs. 12.0 ± 1.6 pg/ml in NLR. Angiogenin levels were different between LR and NLR blood, 0 pg/ml (undetectable) vs. 44.2 ± 3.7 pg/ml ( p < 0.001). Storage time did not affect concentration. TNF-α levels were not different between LR and NLR blood, and there was no storage time effect on concentration. EGF and PDGF levels increased with storage time in NLR blood only, 216.4 ± 3.8 pg/ml at D.1 vs. 1,436.4 ± 238.6 pg/ml at D.42 for EGF ( p = 0.001), and 61.6 ± 6.0 pg/ml at D.1 vs. 76.5 ± 1.7 pg/ml at D.42 ( p = 0.003) for PDGF. Inhibition of EGF reduced migration in Pan02 cells treated with D.42 NLR blood, 245.9 ± 11.2 vs. 164.6 ± 10.6 cells/hpf ( p < 0.001). Inhibition of PDGF had no effect on Pan02 migration and reduced cell proliferation in cells treated with D.42 NLR, 181.1 ± 1.5% over control vs. 157.5 ± 2.1% ( p < 0.001). Conclusion: Pro-cancer cytokines that can augment tumor progression were identified in pRBCs. Some of these factors are present in fresh blood. The soluble factors identified herein may represent possible therapeutic targets to offset negative effects of transfusion. These data stress the need for efforts in cancer patients to reduce transfusion requirements if needed. [ABSTRACT FROM AUTHOR]

The article provides information on a study which investigated the effects of fresh versus stored blood transfusion on clinically relevant outcomes after myocardial infarction (MI). The study used an animal model to objectively measure the effects of transfusion and blood storage on cardiac function and tissue injury. The research found that prolonged storage of blood negates the beneficial effects of fresh blood transfusion.

Background—Intravascular red cell hemolysis impairs nitric oxide (NO)-redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we hypothesized could impair vascular function and contribute to the putative storage lesion of banked blood. Methods and Results—We now find that storage of human red blood cells under standard blood banking conditions results in the accumulation of cell-free and microparticle-encapsulated hemoglobin, which, despite 39 days of storage, remains in the reduced ferrous oxyhemoglobin redox state and stoichiometrically reacts with and scavenges the vasodilator NO. Using stopped-flow spectroscopy and laser-triggered NO release from a caged NO compound, we found that both free hemoglobin and microparticles react with NO about 1000 times faster than with intact erythrocytes. In complementary in vivo studies, we show that hemoglobin, even at concentrations below 10 μmol/L (in heme), produces potent vasoconstriction when infused into the rat circulation, whereas controlled infusions of methemoglobin and cyanomethemoglobin, which do not consume NO, have substantially reduced vasoconstrictor effects. Infusion of the plasma from stored human red blood cell units into the rat circulation produces significant vasoconstriction related to the magnitude of storage-related hemolysis. Conclusions—The results of these studies suggest new mechanisms for endothelial injury and impaired vascular function associated with the most fundamental of storage lesions, hemolysis. [ABSTRACT FROM AUTHOR]

Abstract: Platelet storage lesion (PSL), correlating with reduced in vivo recovery/survival and hemostatic capacity after transfusion, is characterized essentially by morphological and molecular evidence of platelet activation and energy consumption in the medium. Processes that limit shelf-life are multifactorial, and include both necrosis and apoptosis. PSL is greatly influenced by factors including duration of storage, temperature, ratio of platelet number to media volume, solution composition with respect to energy content and buffering capacity, and gas permeability of the container. Recent progress for slowing PSL has been made with storage media that more effectively fuel ATP production and buffer the inevitable effects of metabolism. Improved oxygen-permeability of containers also helps to maintain aerobic-dominant glycolysis. Patients stand to benefit from platelet products of higher intrinsic quality that store well until the moment of transfusion. [Copyright &y& Elsevier]

The mechanical fragility index (MFI) is an in vitro measure of sublethal injury to RBCs. In our previous experiments, we demonstrated that an increase in sublethal injury (increasing MFI) was a component of the RBC storage lesion, and that the MFI was significantly higher amongst the RBC units from male donors compared to pre-menopausal female donors during storage. It was hypothesized that hormonal or menstrual factors contributed to this difference. In this study, we found that RBC units donated by post-menopausal women demonstrated an MFI that was significantly higher than those donated by pre-menopausal women throughout storage. [ABSTRACT FROM AUTHOR]

Conventional quality control studies of the shelf life of RBC units do not consider cold chain interruptions that occur during cross-matching or between the release of RBCs from the blood bank and their return from the ward. These interruptions may, however, lead to a considerable loss of quality. On the other hand, differences in the quality of RBCs may derive from the different manufacturing processes employed in various blood centres. One day after the expiry date of the RBC unit, we analysed complete blood count, blood gas, potassium, LDH, hydroxybutyrate dehydrogenase, glucose, lactate, total and free haemoglobin (Hb) and ATP and compared the results with regard to the frequency of storage interruptions and to two manufacturers of these RBCs. We could not find any correlations between the frequency of interruptions (0-11) and these parameters in any of the data sets. However, we found significant differences when comparing the two suppliers. RBCs of manufacturer A ('A', inline filtration of whole blood) contained 25% more Hb than those of manufacturer B ('B', inline filtration after buffy coat reduction). Sixteen percentage of 'A'-RBC, but none of 'B'-RBC, exceeded a haemolysis of 0·8%. Transitory interruptions of cold chain do not measurably impair the quality of RBCs. The effect on storage of RBCs in the blood bank is not as significant a factor as the differences that exist between RBC manufacturing procedures. [ABSTRACT FROM AUTHOR]

To contribute to the understanding of the biochemical changes associated with the RBC storage lesion. To investigate changes in O equilibrium and on/off kinetic rates during routine cold storage. As RBCs are stored between 1 and 6°C numerous biochemical changes occur within the RBCs, including changes in the properties of the haemoglobin itself. This study serially analysed for the first time the O equilibrium and on/off kinetic rates across the RBC membrane during routine storage. The oxygen binding ( k) and offloading ( k) constants were measured in fresh RBCs and then in AS-5-preserved RBCs at weekly intervals, along with oxygen equilibrium curves (OECs), 2,3-Diphosphoglycerate (2,3-DPG), p50 and the Hill number ( n). The k increased slightly as the 2,3-DPG and p50 decreased during storage, whereas the k remained largely unchanged. The OECs demonstrated the expected increase in O affinity, whereas the Hill number was unchanged during storage. In spite of the biochemical, structural and functional changes associated with the storage of RBCs, their in vitro interactions with oxygen were largely preserved through 42 days of storage. [ABSTRACT FROM AUTHOR]

The effect of the age of RBCs on anti-RBC alloimmunization has not been investigated in previous studies of the RBC storage lesion. D-negative recipients of at least 1 D-positive RBC unit were identified. Responders produced an anti-D, while nonresponders had not made anti-D when the database was searched. The 2 groups were matched for age, sex, length of serologic follow-up, and hospital location. There were 29 responders and 58 nonresponders. The median number of all RBCs transfused to the responders was 6, vs 10 for the nonresponders (P < .01); the median age of the RBCs was 15 vs 14 days, respectively (P = .70). Responders received a median of 3 D-positive RBC units vs 4 D-positive RBCs for nonresponders (P = .02); median ages of the D-positive RBCs were 16 vs 14 days, respectively (P = .21). There was no association between the age of transfused RBCs and the likelihood of anti-D alloimmunization. [ABSTRACT FROM AUTHOR]

Background: The structural and biochemical changes to erythrocytes during storage, called ‘storage lesion’, are important factors that contribute to decreases in the efficacy and safety of blood transfusions. However, the biochemical mechanisms are only partly understood. Study design and methods: Fresh whole blood in citrate phosphate dextrose anticoagulant was preserved in storage bags at 1–4°C for over 20 days. Aliquots of stored blood were withdrawn for analysis at the 1st, 5th, 10th, 15th and 20th day of storage. Whole blood viscosity, plasma reactive carbonyl species, erythrocyte membrane protein carbonylation, protein (tryptophan) fluorescence and the contents of thiols were quantified concurrently. Results: There were significant increases in blood viscosity and plasma reactive carbonyl species level during storage. There were significant time-dependent increases in membrane protein carbonylation, increases in protein (tryptophan) fluorescence and a decrease in the content of thiols. Conclusion: Reactive carbonyl species, by attacking the amino and/or sulfhydryl groups of erythrocyte membrane proteins, induce a series of structural alterations in erythrocytes. These lead to an increase in blood viscosity and reduce the efficacy and safety of storage and transfusion. [ABSTRACT FROM AUTHOR]

The article presents a study on the role of gene expression in the autologous transfusion of blood in sports. It mentions that the study is intended to discover potential detection method that would determine autologous blood doping in sports after the reinfusion of autologous red blood cells (RBCs). The study uses six healthy male volunteers who was subjected into transfusion medicine. It was then found out that the transfusion could be a practicable method to detect autologous blood doping.

Abstract: Objective: Few studies have shown that aged packed red blood cells (RBC) transfusion negatively influenced the outcome of ICU patients, probably related to storage lesions which could be decreased by leukodepletion of RBC. The purpose of this study was to evaluate the impact of aged leukodepleted-RBC pack, on the outcome of ICU patients. Design: Retrospective, observational, cohort study in a Medical Intensive Care Unit. Patients: Consecutive patients admitted during the years 2005 and 2006, and requiring a transfusion. We recorded patient''s demographic data, number of RBC unit and age of each RBC, length of ICU, mortality during ICU stay. Results: Five hundred and thirty-four patients were included with global mortality was 26.6%, length of stay in ICU six days (3–14) and SAPS II 48 (35–62). RBC equaling to 5.9 were transfused per patients (22.7%<14 days and 57.3%<21 days). The number of RBC was significantly higher in the dead patients group, but the rate of RBC stored less than 21 days was not different (54% versus 60%; p =0.21). In a multivariate logistic model, independent predictors of ICU death were SAPS II (OR=1.02 per point, p <0.001), number of RBC (OR=1.08 per RBC, p <0.001), length of stay in ICU (p <0.001). Similar results were obtained while introducing the age of RBC as time dependent covariates in a multivariate Cox''s model. Conclusions: RBC transfused in our ICU are old. The ICU outcome is independently associated with the number of leucodepleted RBC transfused, but not with their age. [Copyright &y& Elsevier]

Abstract: Background and objects: Lipids with platelet activating factor (PAF)-like activity in supernatant of packed red blood cells (PRBC) cause priming of the neutrophil respiratory burst. This effect increases with length of storage. Washing of PRBC has been considered as a means to eliminate this effect; however, the role of the cellular component was not evaluated independently of the supernatant. The source of the inflammatory lipids of the supernatant is likely to be cell membranes altered during ageing in storage and therefore, washing will not eliminate neutrophil priming caused by transfusion of aged PRBC units. The ability of washed PRBC to prime mononuclear cells for another known effect of PAF, the production of IL-8, and the probability that this lipid activity is present on microparticles in PRBC supernatant were also investigated. Materials and methods: At collection 10 units of whole blood were split into two equal aliquots one filtered and one unfiltered. PRBC were prepared and stored at 4°C in CPD-AS5. Each week, fresh neutrophils were incubated with samples of washed PRBC and fixed. Change in CD11b, a marker known to increase on the surface of primed neutrophils, was determined by flow cytometry. To determine whether neutrophil priming ability of PRBC supernatant is contained on microvesicles, centrifuged and uncentrifuged supernatant samples were incubated with fresh neutrophils and change in CD11b expression was determined. Plasma IL-8 levels were also measured after exposure of monocytes from fresh whole blood to filtered and unfiltered washed PRBC with and without the addition of fMLP. Results: Washed PRBC caused a 50–116% increase in CD11b neutrophil surface expression over baseline expression. Filtration of whole blood at collection reduced this CD11b up-regulation by 25–34%. Reduction of priming ability by filtration began on the day of collection and persisted for the storage life of the units. Centrifugation resulted in a reduction of CD11b up-regulation of 11–28% compared with unspun supernatant. Incubation of unfiltered PRBC resulted in priming of mononuclear leukocytes for IL-8 production with a 73–109% increase over baseline, but no increase over baseline was seen for incubation with filtered blood. Conclusion: Washing does not eliminate the ability of PRBC units to prime neutrophils and mononuclear cells, because the cellular component of PRBC, in addition to the supernatant, induces priming. Leukodepletion filters significantly reduce these effects compared with unfiltered PRBC. The in vitro beneficial effect of filtration lasts for the shelf life of 42 day units. The ability of PRBC supernatant to prime neutrophils is present on microvesicles. [Copyright &y& Elsevier]

Under Blood Bank storage conditions, platelet undergo a series of physical, metabolic and physiological changes that are denominated "platelet storage lesion" (PSL). This condition depends on several factors: the platelets number and the methodology used for the preparations of platelet concentrates (PC), type of storage bag, the number of leukocytes present in the cell unit, cytokines release, among others. All these factors may produce platelet activation and thus affect the quality of the product, which would be reflected in a shorter survival of the transfused platelets. Based on the previous knowledge, we hypothesized that early removal of leukocytes from the apheresis concentrate will diminish platelets "activation/lesion" during storage. We studied twenty PC obtained by two methods of apheresis that differed in the number of residual leukocytes remaining in the final product. Therefore, two products were obtained: a leukoreduced PC (Cobe Spectra) and a standard PC (3000 Baxter CS extra). The determinations were made at day zero (pre-storage) and at the fifth day of storage. The evaluation included markers present in platelets membrane, such as, p-selectin (CD62-P), glycoprotein Ib (CD42b), phosphatydilserine expression (PS), Tissue Factor (CD142) and microparticles (MPs) generation, that were analyzed by flow cytometry. Cytokines released by leukocytes or activated platelet (IL-1. IL-6, TNF and RANTES), were analyzed by the ELISA technique. The most important marker of platelets activation, CD62-P, was significantly more increased in leukoreduced CP (P: 0.001) than in the standard method (p: 0.02). The expression of GPIb diminished significantly only in non-leukoreduced platelets (p: 0.01). With regard to the procoagulant activity of platelets, a significant increase in the PS expression was observed on the external face of the platelet membranes (p: 0.019) and on MPs (p: 0.025) only in leukoreduced preparations, changes that were accompanied by a very slight increase of tissue factor expression (p: 0.055). The determinations of soluble cytokines did not show significant changes with the storage of platelets. Our results demonstrated that the presence of leukocytes in the platelet concentrates obtained by apheresis, do not play an important role in the storage lesion phenomenon. On the other hand we found that, although changes in platelets exist during their in vivo aging, these are mile and unexpectedly they were more significant in the leukoreduced units. [ABSTRACT FROM AUTHOR]

The majority of intensive care unit (ICU) patients will receive a blood transfusion at some point during the course of their ICU stay, generally in an attempt to increase oxygen delivery and hence tissue oxygenation. The efficacy of red blood cell (RBC) transfusion can be evaluated through its effects on patient mortality or morbidity, or more simply by its effects on tissue oxygenation. Review of the available literature shows controversial results, with some studies showing that RBC transfusion may be efficacious while others do not. The true challenge lies in determining which patients will benefit from transfusion and those in whom it may be safe to delay or withhold transfusion. In this article, several key factors influencing the systemic and regional efficacy of blood transfusion will be reviewed. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The aim of this investigation was to provide evidence that leukocyte depleted whole blood meets the requirements for transfusion of the European Council and thus may be an alternative to leukocyte and plasma depleted packed red blood cells in autologous blood predeposit for patients undergoing elective surgery programs. Material and methods: Standard units of 450mL blood were collected from 25 healthy male volunteers. Leukocyte depletion was done via inline filtration 4h after collection. Storage lesion was assessed by measuring the release of K+, LDH, free hemoglobin, and lactate into the storage medium, as well as by the increase of hemolysis, the decrease of pH and consumption of glucose over a storage period of 35 days. As surrogate marker for red cell quality the intracellular concentrations of adenine nucleotides [ATP, ADP, AMP] were determined. Results: The extent of storage lesion remained within the ranges of standard liquid storage conditions. Hemolysis was far below the threshold of 0.8% in all WB units at the end of their shelf life. Only minor changes of intracellular adenine nucleotide levels were measured indicating a preserved function of red blood cells in leukocyte depleted whole blood. At the end of shelf life 70%±18% of initial ATP levels were detected. Conclusion: Based on our data we propose that leukocyte depleted whole blood, stored for 35 days can be an option in the autologous blood supply as it meets the requirements for transfusion of the European Council. [Copyright &y& Elsevier]

Data on the quality of platelet concentrates (PC) produced by the buffy coat method and stored beyond 5 days in plasma are limited. We therefore evaluated the quality of PCs prepared by leucocyte depletion of whole blood (Terumo WBSP,n = 10) or a buffy coat pool (Pall Autostop,n = 10), and stored for 7 days in plasma by assessing platelet parameters and markers of platelet activation.In both types of PC, levels of glucose decreased during storage but were not totally depleted (> 11 mM on day 7). In contrast, lactate levels increased on storage and was consistently<20 mM throughout, with pH maintained at>6·8 in all units. Hypotonic shock response scores were>47% in all units at day 7. On day 1, markers of platelet activation were significantly higher in WBSP PC, but by day 7 were similar for percentage CD63+ and CD62P + (40%) with levels of platelet microparticles and annexin V binding two-fold higher in WBSP. The expression of CD61 did not alter during storage and the percentage of platelets expressing CD42b was > 88% in all units on day 7. RANTES (Regulated on activation, normal, T-cell expressed and secreted) and TGFβ released from platelets by day 7 was < 800 ng/ml and 90 ng/ml, respectively. C3adesarg increased throughout storage in both types of PC, but without a commensurate increase in the terminal complex SC5b-9 or activation of factor XII.Our data indicates that thein vitrocharacteristics of PCs prepared using these methods is maintained over storage for 7 days in plasma and is not associated with significant deterioration of platelet function.In vitrofunction of platelet concentrates prepared by either filtration of whole blood, or pooled buffy coats [ABSTRACT FROM AUTHOR]