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Screening for the risk of thromboembolism (TE) due to tranexamic acid (TXA) in patients with severe traumatic injury has not been performed in randomized clinical trials. Our objective was to determine if TXA dose was independently-associated with thromboembolism.This is a secondary analysis of a single-center, double-blinded, randomized controlled trial comparing placebo to a 2-g or 4-g intravenous TXA bolus dose in trauma patients with severe injury. We used multivariable discrete-time Cox regression models to identify associations with risk for thromboembolic events within 30 days post-enrollment. Event curves were created using discrete-time Cox regression.There were 50 patients in the placebo group, 49 in the 2-g, and 50 in the 4-g TXA group. In adjusted analyses for thromboembolism, a 2-g dose of TXA had an hazard ratio (HR, 95% confidence interval [CI]) of 3.20 (1.12-9.11) (p = .029), and a 4-g dose of TXA had an HR (95% CI) of 5.33 (1.94-14.63) (p = .001). Event curves demonstrated a higher probability of thromboembolism for both doses of TXA compared to placebo. Other parameters independently associated with thromboembolism include time from injury to TXA administration, body mass index, and total blood products transfused.In patients with severe traumatic injury, there was a dose-dependent increase in the risk of at least one thromboembolic event with TXA. TXA should not be withheld, but thromboembolism screening should be considered for patients receiving a dose of at least 2-g TXA intravenously for traumatic hemorrhage.

Renewed interest in low titer group O whole blood (LTOWB) transfusion has led to increased utilization in adult trauma centers; little is known regarding LTOWB use in pediatric centers.A survey of LTOWB utilization at American pediatric level 1 trauma centers.Responses were received from 43/72 (60%) centers. These institutions were primarily urban (84%) and pediatric-specific (58%). There were 16% (7/43) centers using LTOWB, 7% (3/43) imminently initiating an LTOWB program, 47% (20/43) with interest but no current plan to develop a LTOWB program, and 30% (13/43) with no immediate interest in an LTOWB program. For the hospitals actively or imminently using LTOWB, 70% (3/10) have a minimum recipient weight criterion, 60% (6/10) have a minimum age criterion, and 70% (7/10) restrict the maximum volume transfused. Before the patient's RhD type becomes known, 30% (3/10) use RhD negative LTOWB for males and females, 40% (4/10) use RhD positive LTOWB for males and RhD negative LTOWB for females, 20% (2/10) use RhD positive LTOWB for males and RhD negative RBCs for females, and 10% (1/10) use RhD positive LTOWB for both males and females. Maximum LTOWB storage duration was 14-35 days and units nearing expiration were used for non-trauma patients (40%), processed to RBC (40%), and/or discarded (40%). The most common barriers to implementation were concerns about inventory management (37%), wastage (35%), infrequent use (33%), cost (21%) and unclear efficacy (14%).LTOWB utilization is increasing in pediatric level 1 trauma centers in the United States.

Background Recently revisited products like low-titer group O whole blood (LTOWB) and novel applications of group A as a universal donor of plasma are being used for trauma resuscitation. A survey of American Level 1 trauma centers was performed to elucidate the extent to which these products are currently employed. Methods A survey was written that probed into the current use of blood products in trauma resuscitation with specific emphasis on LTOWB and group A plasma. A list of adult civilian Level 1 trauma centers in the continental USA was obtained from two public surgery and trauma focused websites. An email was then sent to each center's transfusion service medical director or laboratory manager providing them with a link to the online survey. Results Responses were received from 103/187 (55%) adult civilian Level 1 trauma centers. For the resuscitation of trauma patients, group A plasma was used at 94/103 (91%) centers, while LTOWB was used at 43/103 (42%) centers. There were 39/103 (38%) centers that used both products. At 62/94 (66%) of the centers that used group A plasma, there was no limit on the number of units that could be administered, while an unlimited number of LTOWB units could be used at 5/43 (12%) of the centers that used LTOWB. RhD-positive LTOWB could be transfused to RhD-negative or RhD-type unknown females of childbearing potential at 22/43 (51%) of centers. Conclusion The use of group A plasma and LTOWB in trauma is increasing at American Level 1 trauma centers.

Background Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (

To describe critically ill children's coagulation profile with the multisystem inflammatory syndrome (MIS-C) related to coronavirus.Single-center, observational study at a tertiary, pediatric intensive care unit (PICU) in children aged 1 month to 18 years.Sixteen children, with a median age of 5.4 years (interquartile range [IQR] 2.1, 11.75), 56% female, admission Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score of 3.5 (IQR 2, 5), and median PICU length of stay 3 days (IQR 1.5, 4), met criteria of MIS-C. All patients received acetylsalicylic acid (80-100 mg/kg) and none received anticoagulation. Sixty-three percent (10/16) of children had out-of-normal range values on thromboelastography (TEG) (44% [7/16] with hypercoagulability and 19% [3/16] with hypocoagulability). Of those with hypercoagulability, 19% (3/16) had rapid clot formation, and 25% (4/16) had increased clot strength. In 69% (11/16) of children, there was impaired fibrinolysis (0% lysis at 30 minutes) on TEG. Seventy-five percent (12/16) of children had out-of-normal range value on standard coagulation assays (37.5% [6/16] with hypocoagulability and 37.5% [6/16] with hypercoagulability). TEG-G (clot strength as measured by TEG) value (ρ -.553, p = .033) and platelet count (ρ -.840, p .0001) were correlated with admission PELOD-2 score. TEG-G value (ρ -.506, p = .04) and platelet count (ρ -.539, p = .03) were correlated with the duration of intensive care unit stay.Coagulation abnormalities are frequent in children with MIS-C. TEG parameter and platelet count are correlated with the severity of multiorgan dysfunction and the duration of intensive care stay. Multicenter studies are needed to confirm the clinical implications of these coagulation abnormalities.

Background Low-titer group O whole-blood (LTOWB) is being used for children with life-threatening traumatic bleeding. A survey was conducted to determine current LTOWB utilization and interest in participation in a randomized control trial (RCT) of LTOWB versus standard blood component transfusion in this population. Study design and methods Transfusion medicine (TM) directors and pediatric trauma directors at 36 US children's hospitals were surveyed by e-mail in June 2020. Hospitals were selected by participation in the Massive Transfusion Epidemiology and Outcomes in Children Study or being among the largest 30 children's hospitals by bed capacity per the Becker Hospital Review. Results The response rate was 83.3% (30/36) from TM directors and 88.9% (32/36) from trauma directors. The median of massive transfusion protocol activations for traumatic bleeding was reported as 12 (IQR 5.8-20) per year by TM directors. LTOWB was used by 18.8% (6/32) of trauma directors. Survey responses indicate that 86.7% (26/30) of TM directors and 90.6% (29/32) of trauma directors either moderately or strongly agree that a LTOWB RCT is important to perform. About 83.3% (25/30) of TM directors and 93.8% (30/32) of trauma directors were willing to participate in the proposed trial. About 80% (24/30) of TM directors and 71.9% (23/32) of trauma directors would transfuse RhD+ LTOWB to male children, but fewer would transfuse Rh + LTOWB to females [20% (6/30) TM directors and 37.5% (12/32) of trauma directors]. Conclusions A majority of respondents supported an RCT comparing LTOWB to component therapy in children with severe traumatic bleeding.

Background Epstein-Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post-transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post-transplant EBV outcomes among pediatric allogeneic HSCT recipients. Methods We used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice-Williams-Petersen models were used to analyze risk factors for post-transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV-VL), and preemptive use of rituximab, an effective therapy against PTLD. Results Females were at higher risk for increasing EBV-VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33-6.03]) and rituximab use (HR = 3.08 [1.14-8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74-1.99]) and recurrence risks (HR=1.05 [0.70-1.58]) compared to males. EBV DNAemia was associated with recipient pre-transplant EBV seropositivity (HR = 2.47 [1.17-5.21]) and with graft from an EBV-positive donor (HR = 3.53 [1.95-6.38]). Anti-thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47-19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03-0.63]). Conclusion This study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV-VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV-VL and the use of rituximab) include female sex and ATG use.

Aims/objectives The aim of this study was to evaluate the hemostatic consequences of whole blood leukoreduction (LR). Background Whole blood is being used for trauma resuscitation in the military, and an increasing number of civilian trauma centres across the nation. The benefits of LR, such as decreased infectious and transfusion-related complications, are well established, but the effects on hemostatic parameters remain a concern. Methods Twenty-four units of whole blood were assigned to one of the four groups: non-leukoreduced (NLR), leukoreduced at 1 h and a height of 33 in. (LR-1), leukoreduced at 4 h and a height of 33 in. (LR-4(33)), or leukoreduced at 4 h and a height of 28 in. (LR-4(28)). Viscoelastic parameters, platelet aggregation, cell counts, physiological parameters and thrombin potential were evaluated immediately before and after LR, and on days 1, 7, 14 and 21 following LR. Results The viscoelastic parameters and thrombin generation potential were unchanged between the groups. Platelet aggregation was reduced in the LR-1 group compared with NLR after 7 days. The LR-4(28) group also showed a trend of reduced platelet aggregation compared with NLR. Aggregation in LR-4(33) was similar to NLR throughout the storage time. Physiological and electrolyte changes over the whole blood storage period were not affected by LR. Conclusion Our study shows that whole blood can be LR at 4 h after collection and a height of 33 in. while maintaining platelet count and without altering platelet function and hemostatic performance.

Background The use of low titre group O whole blood (LTOWB) is increasing at civilian transfusion services in the United States and around the world as it has several advantages over conventional components for the resuscitation of traumatically injured and massively bleeding patients. This report documents the implementation of these LTOWB programmes. Methods The AABB/THOR (Trauma, Hemostasis, and Oxygenation Research network) working party developed an electronic survey that was sent to the medical directors of transfusion services where an LTOWB programme had been implemented. Various aspects of the transfusion service's practice were explored. Results There were 27 respondents from four different countries. The majority of the respondents (24/27, 89%) were from the United States, while the others were from Israel, Norway and the United Kingdom. At the 20 sites with a limit on the number of LTOWB units for transfusion in massive bleeding, the average (SD) was 4 (1). Most respondents, 20/27 (74%), use LTOWB for trauma patients only, and the majority, 16/27 (59%), use leucoreduced LTOWB. The most common titre threshold was

The AABB compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine. An abridged version of this work is being made available in TRANSFUSION, with the full-length report available as Appendix S1 (available as supporting information in the online version of this paper).Papers published in late 2017 and 2018 are included, as well as earlier papers cited for background. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed.The following topics are covered: "big data" and "omics" studies, emerging infections and testing, platelet transfusion and pathogen reduction, transfusion therapy and coagulation, transfusion approach to hemorrhagic shock and mass casualties, therapeutic apheresis, and chimeric antigen receptor T-cell therapy.This synopsis may be a useful educational tool.

Background Retrospective studies suggested that storage age of RBCs is associated with inflammation and thromboembolism. The Red Cell Storage Duration Study (RECESS) trial randomized subjects undergoing complex cardiac surgery to receive RBCs stored for shorter versus longer periods, and no difference was seen in the primary outcome of change in multiple organ dysfunction score. Study design and methods In the current study, 90 subjects from the RECESS trial were studied intensively using a range of hemostasis, immunologic, and nitric oxide parameters. Samples were collected before transfusion and on Days 2, 6, 28, and 180 after transfusion. Results Of 71 parameters tested, only 4 showed a significant difference after transfusion between study arms: CD8+ T-cell interferon-γ secretion and the concentration of extracellular vesicles bearing the B-cell marker CD19 were higher, and plasma endothelial growth factor levels were lower in recipients of fresh versus aged RBCs. Plasma interleukin-6 was higher at Day 2 and lower at Days 6 and 28 in recipients of fresh versus aged RBCs. Multiple parameters showed significant modulation after surgery and transfusion. Most analytes that changed after surgery did not differ based on transfusion status. Several extracellular vesicle markers, including two associated with platelets (CD41a and CD62P), decreased in transfused patients more than in those who underwent surgery without transfusion. Conclusions Transfusion of fresh versus aged RBCs does not result in substantial changes in hemostasis, immune, or nitric oxide parameters. It is possible that transfusion modulates the level of platelet-derived extracellular vesicles, which will require study of patients randomly assigned to receipt of transfusion to define.

INTRODUCTION AND AIMS Given the increase in cannabis availability and use in North America, identification of risk factors for cannabis use and dependence is paramount. One factor that may be associated with various cannabis-related adverse outcomes is the context in which it is used. This secondary analysis study sought to examine the extent to which the social context of cannabis use is related to patterns of use and associated harms. DESIGN AND METHODS One hundred and eighty-eight adult cannabis users were community-recruited in Halifax, Canada. Participants took part in a face-to-face structured interview where they provided information about the social context of their most recent cannabis-using occasion and about their patterns of, and motives for, cannabis use. RESULTS Compared to individuals reporting their most recent cannabis-using occasion as social, solitary users (n = 55) were significantly more likely to screen positive for psychosis, endorse more symptoms of cannabis abuse/dependence, report using cannabis to cope, and use cannabis on more days within the previous 30 days. On the other hand, social users were significantly more likely to report using alcohol in addition to cannabis during their most recent cannabis-using occasion (all P

INTRODUCTION There has been interest in using human blood products in nonhuman primate models of trauma to supplement human studies and to provide evidence to guide novel trauma resuscitation strategies. The compatibility of human RBCs has not been extensively studied in nonhuman primate species. METHODS Whole blood samples were collected from five healthy, nontransfused, not previously pregnant Chinese-bred rhesus macaques. The whole blood was centrifuged, and the plasma was decanted from each sample. Group O-negative human RBCs were mixed with the plasma from the rhesus macaque monkeys. Compatibility testing was performed by an immediate spin test and polyspecific and monospecific anti-human globulin (AHG) tests in glass tubes. RESULTS Immediate spin testing revealed three out of five plasma samples (60%) from rhesus macaques caused at least 1+ agglutination with the human RBCs. Polyspecific anti-human globulin (AHG) tests demonstrated that two of five plasma samples (40%) from rhesus macaques caused at least 1+ agglutination with the human RBC, while the monospecific AHG testing revealed that the incompatibility was caused by C3d, not IgG. CONCLUSION Human RBCs are not compatible with the plasma of some, but not all, Chinese-bred rhesus macaques.

BACKGROUND There is a resurgence in the use of low-titer group O whole blood (LTOWB) for hemorrhagic shock. We hypothesized the use of LTOWB compared to component therapy (CT) would be independently associated with improved 24-hour mortality. STUDY DESIGN AND METHODS In this prospective observational study, trauma patients 18 years of age or older with massive transfusion protocol activations were included from August 17, 2018, to May 14, 2019. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour blood product totals, multiple organ dysfunction scores (MODS), and 28-day mortality. Multivariable logistic regression (MVLR) and Cox regression were performed to determine independent associations. RESULTS There were no clinically meaningful differences in measures of injury severity between study groups (CT, n = 42; LTOWB, n = 44). There was no difference in MODS between study groups. The unadjusted mortality was not statistically different between the study groups (9/42 [21%] for CT vs. 7/44 [16%] for LTOWB; p = 0.518). In the MVLR model, LTOWB increased the odds of 24-hour survival by 23% (odds ratio 0.81, 95% confidence interval 0.69-0.96; p = 0.017). Adjusted survival curve analysis indicated improved survival at both 24 hours and 28 days for LTOWB patients (p < 0.001). Further stratification showed an association between LTOWB use and survival when maximum clot firmness (MCF) was 60 mm or less (p = 0.009). CONCLUSIONS The use of LTOWB is independently associated with improved 24-hour and 28-day survival, and does not increase organ dysfunction at 72 hours. Use of LTOWB most impacted survival of patients with reduced clot firmness (MCF ≤60 mm). Collectively, these data support the clinical use and continued study of LTOWB for hemostatic resuscitation.

Background The objective of this study was to assess transfusion strategies and outcomes, stratified by the combat mortality index, of casualties treated by small surgical teams in Afghanistan. Resuscitation that included warm fresh whole blood (FWB) was compared to blood component resuscitation. Study design and methods Casualties treated by a Role 2 surgical team in Afghanistan from 2008 to 2014 who received 1 or more units of red blood cells (RBCs) or FWB were included. Patients were excluded if they had incomplete data or length of stay less than 30 minutes. Patients were separated into two groups: 1) received FWB and 2) did not receive FWB; moreover, both groups potentially received plasma, RBCs, and platelets. The analysis was stratified by critically versus noncritically injured patients using the prehospital combat mortality index. Kaplan-Meier plot, log-rank test, and multivariable Cox regression were performed to compare survival. Results In FWB patients, median units of FWB and total blood product were 4.0 (interquartile range [IQR], 2.0-7.0) and 16.0 (IQR, 10.0-28.0), respectively. The Kaplan-Meier plot demonstrated that survival was similar between FWB (79.1%) and no-FWB (74.5%) groups (p = 0.46); after stratifying patients by the combat mortality index, the risk of mortality was increased in the no-FWB group (hazard ratio, 2.8; 95% confidence interval, 1.2-6.4) compared to the FWB cohort. Conclusion In forward-deployed environments, where component products are limited, FWB has logistical advantages and was associated with reduced mortality in casualties with a critical combat mortality index. Additional analysis is needed to determine if these effects of FWB are appreciable in all trauma patients or just in those with severe physiologic derangement.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high‐quality research in this area to guide optimal resuscitation strategies.

Background The AABB compiles an annual synopsis of the published literature covering important developments in the field of Transfusion Medicine. For the first time, an abridged version of this work is being made available in TRANSFUSION, with the full-length report available as an Appendix S1 (available as supporting information in the online version of this paper). Study design and methods Papers published in 2016 and early 2017 are included, as well as earlier papers cited for background. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed. Results The following topics are covered: duration of red blood cell storage and clinical outcomes, blood donor characteristics and patient outcomes, reversal of bleeding in hemophilia and for patients on direct oral anticoagulants, transfusion approach to hemorrhagic shock, pathogen inactivation, pediatric transfusion medicine, therapeutic apheresis, and extracorporeal support. Conclusion This synopsis may be a useful educational tool.

Red blood cell (RBC) transfusion is common in critically ill, postsurgical, and posttrauma patients in whom both systemic inflammation and immune suppression are associated with adverse outcomes. RBC products contain a multitude of immunomodulatory mediators that interact with and alter immune cell function. These interactions can lead to both proinflammatory and immunosuppressive effects. Defining clinical outcomes related to immunomodulatory effects of RBCs in transfused patients remains a challenge, likely due to complex interactions between individual blood product characteristics and patient-specific risk factors. Unpacking these complexities requires an in-depth understanding of the mechanisms of immunomodulatory effects of RBC products. In this review, we outline and classify potential mediators of RBC transfusion-related immunomodulation and provide suggestions for future research directions.

Building on the successful military experience, interest has been rekindled in transfusing whole blood (WB) early in the resuscitation of traumatically injured civilians, often before their ABO group is known. WB efficiently provides treatment for shock and coagulopathy, as well as platelet hemostatic function, to patients losing large volumes of blood. Unlike group O uncrossmatched red blood cells (RBCs), group O WB contains a substantial amount of plasma, which is incompatible with the RBCs of all non-group O recipients. Thus, when implementing a WB program, it is important to decide how to mitigate the risk of immune-mediated hemolysis. Other questions that a hospital needs to answer before implementing a WB program include determining which patients will be eligible for this product, how many units eligible patients can receive, for how long it should be stored and under what conditions, and how to monitor for adverse events. The donor center needs to consider if the WB should be leukoreduced, how to comply with the AABB's transfusion-related acute lung injury risk mitigation standard, and into which storage solution it should be collected. This report describes the multidisciplinary approach taken to implementing a civilian WB program at a multihospital health care system in the United States.

The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop was supported by the National Heart, Lung, and Blood Institute, NIH; the Department of Defense; the Office of the Assistant Secretary for Health, Department of Health and Human Services; and the Center for Biologics Evaluation and Research, FDA. The workshop reviewed the status and scientific basis of the current regulatory framework and the available scientific tools to expand it to evaluate innovative and future RBC transfusion products. A full record of the proceedings is available on the FDA website (http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm507890.htm). The contents of the summary are the authors' opinions and do not represent agency policy.

The success of whole blood transfusion in military operational settings has engaged a debate on reintroduction of cold-stored whole blood in treatment of critical bleeding in civilian health care. The haemostatic function of platelets stored cold at 4°C has however been questioned. In this review, we discuss the effects of cold storage on platelets, whether stored in whole blood or as platelet concentrates. Cold storage of platelets was abandoned during the 1970s due to reduced circulation time. Haemostatic superiority of cold-stored platelets was however suggested. In vitro studies show reduced risk of bacterial contamination and equal or superior haemostatic qualities in cold-stored platelet concentrates when evaluated by metabolic measures and aggregation response. Data on cold-stored platelet concentrates from thrombocytopenic patients and healthy volunteers indicate improved platelet aggregation and reduced bleeding. A randomized controlled trial in paediatric patients undergoing cardiac surgery, showed reduced blood loss and improved platelet aggregation responses after transfusion with whole blood stored cold for up to 48 h, and platelets stored cold within whole blood for up to 15 days provide similar post-storage platelet viability as platelet concentrates or apheresis platelets stored for less than 3 days. Animal studies also suggest efficacy of cold-stored platelets. A study investigating the effects of cold-stored apheresis platelets in patients undergoing cardiothoracic is currently being performed in Bergen, Norway showing promising results. We conclude that in vitro and clinical studies indicate that cold-stored platelets may be beneficial in treatment of critical bleeding.

Background Several retrospective studies have suggested that transfusion with red blood cells (RBCs) stored for longer periods is associated with increased mortality. The Age of Blood Evaluation (ABLE) study randomized subjects to receive fresh vs. standard issue RBC units and showed no difference in the primary or secondary endpoints of mortality or change in multi-organ dysfunction syndrome (MODS) score. Methods In this study a subset of 100 ABLE subjects were enrolled to measure coagulation and immune parameters. Samples were collected pre-transfusion and on days 2, 6, 28, and 180 post-transfusion. Levels of 16 coagulation parameters, regulatory and functional T cells, 25 cytokines, and 16 markers of extracellular vesicles (EVs) were determined. Results Changes from baseline in levels of protein C, factor V, and EVs expressing phosphatidyl serine and CTLA-4 (CD152) differed between recipients of fresh and standard storage age RBC units, with the vast majority of coagulation and EV markers and all cytokines tested showing no difference between study arms. Although most analytes showed no difference between subjects in the fresh and standard arms of the study, 6 coagulation parameters, 15 cytokines, and 7 EV parameters changed significantly in the period post-transfusion. Discussion Transfusion of fresh vs. standard issue RBC units does not result in substantial changes in coagulation or immune parameters, up to day 35 of RBC storage. Furthermore, significant changes in multiple coagulation and immune parameters are detectable post-transfusion, though causality cannot be determined based on the current study.

BACKGROUND Massive transfusion protocols (MTPs) to address hemorrhage are understudied in children. The objective was to determine the effect of MTP implementation on outcomes of injured children. STUDY DESIGN AND METHODS This was a retrospective comparison of injured children before and after MTP implementation for children less than 18 years old who presented in 2005 to 2014 and received red blood cells (RBCs) within 24 hours of arrival. Children were divided into groups based on pre-/post-MTP implementation and subgrouped based on receipt of massive transfusion (≥40 mL/kg RBCs or ≥80 mL/kg total blood products at 24 hr from arrival). The primary outcome was in-hospital mortality and secondary outcomes were total blood product use, intensive care unit/ventilator/pressor-free days, composite morbidity, and Glasgow Outcome Score. RESULTS A total of 11,995 children presented for trauma care over 9 years; 235 received RBCs. A total of 120 were in the pre-MTP group and 115 in the post-MTP, of whom 26 and 17 received massive transfusion in the pre- and post-MTP groups, respectively; 11 had MTP activations. Children massively transfused after MTP received mean plasma:RBC and platelet (PLT):RBC ratios greater than 1:1 at both 6 and 24 hours with no significant difference in total admission blood product use. There was no difference in in-hospital mortality between pre- and post-MTP groups (24% vs. 19%) or massive transfusion subgroups (54% vs. 47%). There were no differences in secondary outcomes. CONCLUSIONS While we were not able to show improvements in outcome, MTP implementation led to higher plasma and PLT:RBC ratios without an associated change in blood product use or composite morbidity.

BACKGROUND The provision of transfusion support to isolated military or civilian projects may require the use of an emergency donor panel (EDP) for immediate warm fresh whole blood (WFWB). The aim of this short discussion article is to raise and resolve some of the practical aspects for the nonspecialist faced with the emergency collection of WFWB whole blood in the austere medical environment (AME). METHODS AND RESULTS A proposed field EDP questionnaire and triage tool (QTT) is presented. It is designed for the hostile, remote, or austere environment that falls outside normal regulated supply of cold-stored blood products or removed from trained blood collection personnel, where collection may fall to an isolated medical provider. The tool has been drafted based on review of existing guidelines and consultation with practitioners. It serves as a point of reference for local guidelines and has yet to be validated. CONCLUSIONS The use of the EDP is associated with risk; however, it remains the simplest method of providing rapid transfusion support. The best way to manage the risk is to brief and prescreen blood donors before deployment. An abbreviated donor QTT can be an aide to decision making at the time of donation. The tool should be tailored to requirements and underpinned by policy and training.

Hemorrhagic shock is both a local and systemic disorder. In the context of systemic effects, blood loss may lead to levels of reduced oxygen delivery (DO2 ) sufficient to cause tissue ischemia. Similar to other physiologic debts such as sleep, it is not possible to incur a significant oxygen debt and suffer no consequences for lack of timely repayment. While the linkage between oxygen debt and traditional organ failure (renal, hepatic, lung, and circulation) has been long recognized, we should consider failure in two additional linked and very dynamic organ systems, the endothelium and blood. These systems are very sensitive to oxygen debt and at risk for failing, having further implications on all other organ systems. The degree of damage to the endothelium is largely modulated by the degree of oxygen debt. Thus hypoperfusion is believed to begin a cascade of events leading to acute traumatic coagulopathy (ATC). This combination of oxygen debt driven endothelial damage and ATC might be considered collectively as "blood failure" due to the highly connected networks between these drivers. This article presents the implications of oxygen debt for remote damage control resuscitation strategies, such as permissive hypotension and hemostatic resuscitation. We review the impact of whole blood resuscitation and red blood cell efficacy in mitigation of oxygen debt. At last, this article recognizes the need for simple and durable, lightweight equipment that can detect the adequacy of tissue DO2 and thus patient needs for resuscitative care. Point-of-care lactate measuring may be a predictive tool for identifying high-risk trauma patients and occult shock because it provides information beyond that of vital signs and mechanism of injury as it may help predict the level of oxygen debt accumulation and need for resuscitation. Serial measurements may also be valuable as a tool in guiding resuscitative efforts.

Recent combat experience reignited interest in transfusing whole blood (WB) for patients with life-threatening bleeding. US Army data indicate that WB transfusion is associated with improved or comparable survival compared to resuscitation with blood components. These data complement randomized controlled trials that indicate that platelet (PLT)-containing blood products stored at 4°C have superior hemostatic function, based on reduced bleeding and improved functional measures of hemostasis, compared to PLT-containing blood products at 22°C. WB is rarely available in civilian hospitals and as a result is rarely transfused for patients with hemorrhagic shock. Recent developments suggest that impediments to WB availability can be overcome, specifically the misconceptions that WB must be ABO specific, that WB cannot be leukoreduced and maintain PLTs, and finally that cold storage causes loss of PLT function. Data indicate that the use of low anti-A and anti-B titer group O WB is safe as a universal donor, WB can be leukoreduced with PLT-sparing filters, and WB stored at 4°C retains PLT function during 15 days of storage. The understanding that these perceived barriers are not insurmountable will improve the availability of WB and facilitate its use. In addition, there are logistic and economic advantages of WB-based resuscitation compared to component therapy for hemorrhagic shock. The use of low-titer group O WB stored for up to 15 days at 4°C merits further study to compare its efficacy and safety with current resuscitation approaches for all patients with life-threatening bleeding.

The early transfusion of plasma is important to ensure optimal survival of patients with traumatic hemorrhage. In military and remote or austere civilian settings, it may be impossible to move patients to hospital facilities within the first few hours of injury. A dried plasma product with reduced logistical requirements is needed to enable plasma transfusion where medically needed, instead of only where freezers and other equipment are available. First developed in the 1930s, pooled lyophilized plasma was widely used by British and American forces in WWII and the Korean War. Historical dried plasma products solved the logistical problem but were abandoned because of disease transmission. Modern methods to improve blood safety have made it possible to produce safe and effective dried plasma. Dried plasma products are available in France, Germany, South Africa, and a limited number of other countries. However, no product is available in the US. Promising products are in development that employ different methods of drying, pathogen reduction, pooling, packaging, and other approaches. Although challenges exist, the in vitro and in vivo data suggest that these products have great potential to be safe and effective. The history, state of the science, and recent developments in dried plasma are reviewed.

BACKGROUND In current blood banking practices, platelets (PLTs) are stored in plasma at 22°C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known. STUDY DESIGN AND METHODS In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry. RESULTS Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A–induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A–challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs CONCLUSIONS In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22°C, thereby suggesting that Day 5 PLTs are diminished in their ability to attenuate vascular endothelial permeability.

Background Although a majority of the studies conducted to date on platelet (PLT) storage have been focused on PLT hemostatic function, the effects of 4°C PLTs on regulation of endothelial barrier permeability are still not known. In this study, we compared the effects of room temperature (22°C) stored and (4°C) stored PLTs on the regulation of vascular endothelial cell (EC) permeability in vitro and in vivo. Study design and methods Day 1, Day 5, and Day 7 leukoreduced apheresis PLTs stored at 4 or 22°C were studied in vitro and in vivo. In vitro, PLT effects on EC permeability and barrier function, adhesion, and impedance aggregometry were investigated. In vivo, using a mouse model of vascular leak, attenuation of vascular leak and circulating PLT numbers were measured. Results Treatment of EC monolayers with Day 5 or Day 7 PLTs, stored at both 22°C and 4°C, resulted in similar decreases in EC permeability on average. However, analysis of individual samples revealed significant variation that was donor dependent. Additional in vitro measurements revealed a decrease in inflammatory mediators, nonspecific PLT-endothelial aggregation and attenuated loss of aggregation over time to TRAP, ASPI, ADP, and collagen with 4°C storage. In mice, while 22°C and 4°C PLTs both demonstrated significant protection against vascular endothelial growth factor A (VEGF-A)-induced vascular leak 22°C PLTs exhibited increased protection compared to 4°C PLTs. Systemic circulating levels of 4°C PLTs were decreased compared to 22°C PLTs. Conclusions In vitro, 4°C-stored PLTs exhibit a greater capacity to inhibit EC permeability than 22°C-stored PLTs. In vivo, 22°C PLTs provide superior control of vascular leak induced by VEGF-A. This discrepancy may be due to increased clearance of 4°C PLTs from the systemic circulation.

BACKGROUND Providers commonly transfuse sickle cell disease (SCD) patients with fresh red blood cells (RBCs) as treatment for acute chest syndrome (ACS). The objective of this study was to determine if there is an association between the storage duration of RBCs and length of hospitalization and oxygen requirement after transfusion in pediatric SCD patients with ACS. STUDY DESIGN AND METHODS This is a retrospective cohort study of pediatric SCD patients with ACS treated with a simple RBC transfusion over 8.5 years at a single institution. Multivariate generalized estimation equation analysis was used to identify associations between storage duration of RBCs and outcome measures. RESULTS A total of 234 ACS episodes in 131 subjects were included. The median storage duration of the oldest unit of transfused RBCs was 17 days (interquartile range, 11-26). The majority of ACS episodes, 77.4%, were treated with 1 unit of transfused RBCs; 20.9% received 2 units; and 1.7% received 3 or more units of RBCs. There was no association between the storage duration of the oldest unit of transfused RBCs and either duration of hospitalization or supplemental oxygen requirement after transfusion in multivariate analyses. CONCLUSION This retrospective study is one of the first to investigate the role of the storage lesion in children with SCD and does not support the preferential transfusion of fresh RBCs for ACS. Ultimately, a randomized controlled trial is necessary to determine whether the storage age of RBCs affects outcomes for patients with SCD and ACS.