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Background: Reported bleeding incidences following central venous catheter (CVC) placement highly depend on methods of bleeding assessment. To determine the direction and magnitude of the bias associated with retrospective data collection, we used data from the PACER randomized controlled trial and a previous retrospective cohort study. Study Design and Methods: A patient‐level comparison of CVC‐related bleeding severity was made among (1) the prospectively collected clinical bleeding assessment of the PACER trial, (2) centralized assessment of CVC insertion site photographs, and (3) retrospective chart review. Interrater reliability for photographic bleeding assessment and retrospective chart review was assessed using Cohen's κ. The magnitude of underreporting of both methods compared to prospective clinical bleeding assessment at different cutoff points of clinically relevant bleeding was assessed using McNemar's test. Results: Interrater reliability was acceptable for both methods (κ = 0.583 and κ = 0.481 for photographic assessment and retrospective chart review, respectively). Photographic bleeding assessment led to significant underreporting of bleeding complications at all cutoff points. Retrospective chart review led to significant underreporting of minor bleeding complications, with an odds ratio (95% CI) of 0.17 (0.044–0.51) for the cutoff point grade 1 (i.e., self‐limiting or requiring at most 20 min of manual compression) or higher. There was no significant underreporting of major bleeding complications with retrospective chart review. Discussion: Centralized photographic bleeding assessment and retrospective chart review lead to biased bleeding assessment compared to prospective clinical bleeding assessment. [ABSTRACT FROM AUTHOR]

Background: Kaiser‐Permanente Los Angeles Medical Center (LAMC) is a 560 licensed bed facility that provides regional cardiovascular services, including 1200 open heart surgeries annually. In 2021, LAMC explored alternative therapies to offset the impact of pandemic‐driven cryo AHF shortages, and implemented Pathogen Reduced Cryoprecipitated Fibrinogen Complex (also known as INTERCEPT Fibrinogen Complex or IFC). IFC is approved to treat and control bleeding associated with fibrinogen deficiency. Unlike cryo AHF, IFC has 5‐day post‐thaw shelf life with potential operational and clinical benefits. The implementation steps and the operational advantages to the LAMC Blood Bank are described. Study Design and Methods: Eighteen months post‐implementation, the institution reviewed their product implementation experience and compared IFC with cryo AHF with a retrospective review of transfusion service and cardiac post‐op data. Results: IFC significantly decreased product wastage rates and order‐to‐issue time. It did not significantly impact post‐op product utilization or hospital length of stay (LOS) in cardiac surgery patients when compared with cryo AHF. Discussion: Implementation of IFC provides improved product supply stability, shorter turnaround times, and reduced wastage. [ABSTRACT FROM AUTHOR]

Background: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence‐based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes. Study Design and Methods: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581). Results: In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty‐seven outcomes were reported with a mean of 11 (min–max. 4–32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage. Conclusion: There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion. [ABSTRACT FROM AUTHOR]

Background: Low‐titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD‐positive units due to short supply of RhD‐negative LTOWB. Practitioners must choose between using RhD‐positive LTOWB when RhD‐negative is unavailable against the risk to a female of childbearing potential of becoming RhD‐alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD‐negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD‐positive blood for an injured RhD negative female child. Study Design and Methods: A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy. Results: Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD‐positive transfusions for a female child was 4% (1%–14%). This was not different between females with and without a history of severe or fatal HDFN (p =.08 and 0.38, respectively). Conclusion: Alloimmunized mothers would accept the risk of D‐alloimmunization in a RhD‐negative female child for improved survival in cases of life‐threatening bleeding. [ABSTRACT FROM AUTHOR]

Background: Today, with wars raging in Ukraine and the Middle East, the demand for blood is high. Despite this, few companies produce the necessary equipment to draw, store, and transfuse whole blood. This study evaluated the safety and performance of a 3D printed bottle cap in conjunction with a water bottle and some available consumables to draw and store fresh whole blood. Study Design and Methods: Bags of saline, and freshly donated whole blood, was transferred to the water bottle through a 3D printed bottle cap and stored for 72 h. An identical setup, transferring saline to a Terumo blood collection bag was used as control. Performance and safety were evaluated by calculating infusion rate and observing for backflow, respectively. The blood was also tested for hemolysis and bacterial growth at four sampling points. Results: The cap‐and‐bottle setup was faster than control in terms of flow rate when transferring saline (1.53 vs. 1.81 mL/s, p <.001), and non‐inferior to saline control when transfusing blood (1.53 vs. 1.49 mL/s, p =.641). We did not observe any risks of causing the donor iatrogenic harm, and there was no evidence of increased hemolysis. However, there were traces of bacterial contamination in three of six bottles. Conclusion: This study indicates that drawing blood is both feasible and safe, utilizing a 3D printed cap and bottle setup. Flow rate was faster than control, and mechanical properties of the blood were not affected. We were unable to determine the source of bacterial contamination in the blood. [ABSTRACT FROM AUTHOR]

Introduction: The VCM is a point‐of‐care analyzer using a new viscoelastometry technique for rapid assessment of hemostasis on fresh whole blood. Its characteristics would make it suitable for use in austere environments. The purpose of this study was to evaluate the VCM in terms of repeatability, reproducibility and interanalyzer correlation, reference values in our population, correlation with standard coagulation assays and platelet count, correlation with the TEG5000 analyzer and resistance to stress conditions mimicking an austere environment. Methods: Repeatability, reproducibility, and interanalyzer correlation were performed on quality control samples (n = 10). Reference values were determined from blood donor samples (n = 60). Correlations with standard biological assays were assessed from ICU patients (n = 30) and blood donors (n = 60) samples. Correlation with the TEG5000 was assessed from blood donor samples. Evaluation of vibration resistance was performed on blood donor (n = 5) and quality control (n = 5) samples. Results: The CVs for repeatability and reproducibility ranged from 0% to 11%. Interanalyzer correlation found correlation coefficients (r2) ranging from 0.927 to 0.997. Our reference values were consistent with those provided by the manufacturer. No robust correlation was found with conventional coagulation tests. The correlation with the TEG5000 was excellent with r2 ranging from 0.75 to 0.92. Resistance to stress conditions was excellent. Conclusion: The VCM analyzer is a reliable, easy‐to‐use instrument that correlates well with the TEG5000. Despite some logistical constraints, the results suggest that it can be used in austere environments. Further studies are required before its implementation. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life‐threatening hemorrhage (LTH) from all etiologies. Study Design and Methods: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight‐adjusted transfusion volume during LTH. Kruskal–Wallis, chi‐square testing, and multivariable linear regression were used for adjusted analyses. Results: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight‐adjusted total transfusion volumes compared to males (76 (40–150) mL/kg vs. 53 (24–100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0–11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex. Conclusion: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age. [ABSTRACT FROM AUTHOR]

Background: Blood products form the cornerstone of contemporary hemorrhage control but are limited resources. Freeze‐dried plasma (FDP), which contains coagulation factors, is a promising adjunct in hemostatic resuscitation. We explore the association between FDP alone or in combination with other blood products on 24‐h mortality. Study Design and Methods: This is a secondary data analysis from a cross‐sectional prospective observational multicenter study of adult trauma patients in the Western Cape of South Africa. We compare mortality among trauma patients at risk of hemorrhage in three treatment groups: Blood Products only, FDP + Blood Products, and FDP only. We apply inverse probability of treatment weighting and fit a multivariable Cox proportional hazards model to assess the hazard of 24‐h mortality. Results: Four hundred and forty‐eight patients were included, and 55 (12.2%) died within 24 h of hospital arrival. Compared to the Blood Products only group, we found no difference in 24‐h mortality for the FDP + Blood Product group (p =.40) and a lower hazard of death for the FDP only group (hazard = 0.38; 95% CI, 0.15–1.00; p =.05). However, sensitivity analyses showed no difference in 24‐h mortality across treatments in subgroups with moderate and severe shock, early blood product administration, and accounting for immortal time bias. Conclusion: We found insufficient evidence to conclude there is a difference in relative 24‐h mortality among trauma patients at risk for hemorrhage who received FDP alone, blood products alone, or blood products with FDP. There may be an adjunctive role for FDP in hemorrhagic shock resuscitation in settings with significantly restricted access to blood products. [ABSTRACT FROM AUTHOR]

Introduction: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion‐related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life‐threatening bleeding from all etiologies. Methods: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life‐threatening bleeding. Results: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7–14.7). Within 5 days of the life‐threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025–1.239; p‐value.013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion‐related variables were independently associated with the risk of developing ARDS. Conclusion: The use of increased platelet to red blood cell transfusion ratios in children with life‐threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: The use of low titer O whole blood (LTOWB) has expanded although it remains unclear how many civilian trauma centers are using LTOWB. Methods: We analyzed data on civilian LTOWB recipients in the American College of Surgeons Trauma Quality Improvement Program (TQIP) database 2020–2021. Unique facility keys were used to determine the number of centers that used LTOWB in that period. Results: A total of 16,603 patients received LTOWB in the TQIP database between 2020 and 2021; 6600 in 2020, and 10,003 in 2021. The total number of facilities that reported LTOWB use went from 287/779 (37%) in 2020 to 302/795 (38%) in 2021. Between 2020 and 2021, among all level 1–3 designated trauma facilities that report to TQIP LTOWB use increased at level‐1 centers (118 to 129), and level‐2 centers (81 to 86), but decreased in level‐3 facilities (9 to 4). Among pediatric and dual pediatric‐adult designated hospitals there was a decrease in the number of pediatric level‐1 centers (29 to 28) capable of administering LTOWB. Among centers with either single or dual level‐1 trauma center designation with adult centers, the number that administered LTOWB to injured pediatric patients also decreased from 17 to 10, respectively. Conclusions: There was an increase in the number of facilities transfusing LTOWB between 2020 and 2021. The use of LTOWB is underutilized in children at centers that have it available. These findings inform the expansion of LTOWB use in trauma. [ABSTRACT FROM AUTHOR]

Background: Autotransfusion following vaginal delivery has not been as widely adopted and existing data on this topic are limited to small case series. Methods: This is a single‐center retrospective matched cohort study. Deliveries exposed to autotransfusion during obstetric hemorrhage were matched to unexposed controls with obstetric hemorrhage who did not receive autotransfusion. The primary outcome was allogeneic transfusion of packed red blood cells. Planned secondary analyses included change in hemoglobin following delivery, composite maternal safety outcomes, and unplanned postpartum health care utilization. Results: Thirty‐six deliveries exposed to autotransfusion were matched to 144 unexposed controls. There was no significant difference in allogenic transfusion of packed red blood cells in the patients exposed to autotransfusion red with unexposed controls (adjusted OR 1.1; 95% CI 0.5–2.4). Deliveries that received autotransfusion had a less severe pre‐ to post‐delivery decline in hemoglobin compared with unexposed controls across all values of QBL (p =.003). There were no significant differences in maternal morbidity outcomes evaluated in exposed versus unexposed deliveries. Conclusion: Autotransfusion in cases of vaginal obstetric hemorrhage did not attenuate rates of allogenic packed red blood cell transfusion but did result in a less severe pre‐ to postdelivery decline in hemoglobin at discharge. Autotransfusion cases did not have any markers of increased maternal morbidity when compared with a control group. These findings support emerging evidence indicating that autotransfusion of blood lost during vaginal obstetric hemorrhage is a safe and potentially effective tool for use in the management of obstetric hemorrhage. [ABSTRACT FROM AUTHOR]

Tranexamic acid (TXA) has proven mortality benefit if used early after traumatic injury, likely related to a combination of bleeding reduction and other non‐bleeding effects. If TXA is given more than 3 h after traumatic injury, there is a significant and paradoxical increased risk of death due to bleeding. TXA has level 1 evidence for use as a bleeding reduction agent in isolated orthopedic operations, but in polytrauma patients undergoing orthopedic operations, it is not clear if and when TXA is safe or effective once outside the 3‐h window of proven trauma efficacy. [ABSTRACT FROM AUTHOR]

Background: Thrombocytopenia is common in critically ill patients with cancer. However, the association of platelet count with spontaneous bleeding is controversial in critically ill patients and the association with cancer‐related characteristics is unknown. Methods: This observational study includes patients with active cancer and severe thrombocytopenia. A logistic regression model adjusted for confounders was used to evaluate the association of daily platelet count and cancer‐related characteristics (type of cancer and presence of metastasis) with spontaneous bleeding. Confounders were identified using directed acyclic graphs. Results: We screened 5822 patients, 255 (4.4%) met eligibility criteria resulting in 1401 daily observations. Fifty‐three patients (20.8%) had spontaneous bleeding during the intensive care unit stay, 64% presenting minor, and 36% major bleeding. The adjusted odds ratio (OR) for spontaneous bleeding with platelet count between 49 and 20 × 109/L was 4.6 (1.1–19.6), with platelet count between 19 and 10 × 109/L was 14.2 (3.1–66.2), and with platelet count below 10 × 109/L was 39.6 (6.9–228.5). The adjusted OR for spontaneous bleeding in patients with hematologic malignancies was 0.6 (0.4–1.2), and 4.3 (2.0–9.0) for patients with metastatic tumor. Conclusions: In critically ill patients with active cancer and severe thrombocytopenia, lower counts of platelets and presence of metastasis are associated with increased risk of spontaneous bleeding, while hematologic malignancy is not associated with increased risk of spontaneous bleeding. [ABSTRACT FROM AUTHOR]

Background: Prehospital transfusion is a way of improving the management of hemorrhagic shock. In France, prehospital transfusion is struggling to develop, both because of logistical difficulties and particularly restrictive legislation. To comply with this, we propose to store the blood products (BPs) in ground ambulances with refrigerated boxes allowing remote continuous monitoring of storage conditions, called "NelumBox" (Tec4med Lifescience GmbH). To open them, the ambulance's team needs a code that is only given by the Transfusion Center if the request meets all required regulatory criteria. Study Design and Methods: We conducted a prospective simulation‐based feasibility study using dummy BPs. Two ambulances were equipped. Simulations were triggered unexpectedly, including during on‐call hours. The ability to quickly access the BPs was the main judgment criterion. The quality of hemovigilance during these simulations was also examined. Results: Twenty‐two simulations were performed. The ambulance's team was able to access the BPs in 100% of cases. The average waiting time for receiving the unlocking code was 5 min 27 s (SD = 2 min 12 s, MAX = 12 min 00 s). The transfusion traceability was compliant with regulations in 100% of cases. The transfusion center was able to remotely monitor BPs storage conditions for the entire duration of their stockage in the NelumBox. Discussion: The present procedure is efficient, repeatable, and fast. It guarantees a strict transfusion safety without slowdown a severe trauma management, while complying with French regulations. [ABSTRACT FROM AUTHOR]

Background: Antifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI). Study Design and Methods: We conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life‐threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis. Results: Of 448 children included, median (interquartile range) age was 7 (2–15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety‐three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty‐seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p =.002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre‐LTH, and total weight‐adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0–10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis. Conclusion: Administration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Whole blood (WB) reigns superior to component therapy for the treatment of hemorrhagic shock on the battlefield. Though cold storage of WB offers a shelf life of 21 to 35 days, storage lesions and the potential for blood wastage remain. Storing WB in an additive solution (AS) containing apoptotic inhibitors may help preserve blood cell viability and improve blood quality over extended cold storage. Study Design and Methods: Non‐leukoreduced WB was obtained from healthy individuals and dosed with: AS, AS+Necrostatin‐1 (AS+N1), AS+Boc‐D‐fmk (AS+B; apoptosis inhibitor), AS+Q‐VD‐OPh (AS+Q; apoptosis inhibitor), and Control (0.9% saline). Blood bags were kept refrigerated (1°–6°C) for 21 days. Bags were tested on days 0, 7, 14, and 21 for complete blood count, metabolism, clot formation, aggregation function, platelet activation, and red blood cell quality. Results: Platelet count was better preserved in all AS‐containing samples. All groups displayed increased glucose consumption and lactate production with storage. Furthermore, all groups displayed a similar decline in clot strength (max amplitude) over the 21‐day storage period. Bags that received AS displayed greater preservation of GPIIb expression and lower phosphatidylserine exposure. P‐selectin expression was increased in all AS groups. Discussion: Treatment of hemorrhagic shock with WB transfusion is logistically simpler than component therapy. Results from our study suggest that refrigerated WB stored with an AS containing apoptotic and necrotic inhibitors helps better preserve platelet count but does not improve platelet function. The future development of WB ASs is warranted to optimize both platelet quality and hemostatic function. [ABSTRACT FROM AUTHOR]

Introduction: Limb and junctional hemorrhage are leading causes of potentially preventable death among trauma casualties. Hemorrhage control for these regions could be achieved by direct or indirect pressure. The manual pressure points (MPP) involves applying manual pressure on the arterial supply to occlude distal blood flow without the need for specialized equipment. Study Design and Methods: Prospective, non‐randomized, human volunteer, controlled environment study involving 38 healthy military caregivers, with 26 participants attending a short instructional session. During a medical exercise, participants were requested to apply pressure on the supraclavicular and femoral points aiming to stop regional blood flow, measured by distal pulse palpation. The measures recorded included achievement of distal pulse cessation, success in achieving cessation for a full minute, and subjects' pain scores reported after each attempt. Results: All participants succeeded in achieving distal pulse cessation for both the supraclavicular and femoral points for a full minute. The median time to initial success was 3.0 (interquartile range 2.0–5.0) seconds in the supraclavicular point and 4.5 (interquartile range 3.0–6.0) seconds in the femoral point. Pain scores ranging between 0 and 3 were reported by most subjects during supraclavicular (68.4%) and femoral occlusion (84.2%). Conclusion: The MPP technique was highly effective in occluding distal palpable pulses in healthy volunteers when applied to the supraclavicular and femoral arteries. Brief instruction on the technique can potentially improve the chances of achieving hemorrhage control within 5 s. Further research is required to determine efficacy among different populations and providers with varying experience levels. [ABSTRACT FROM AUTHOR]

Background: New blood products are considered for treatment of patients with major hemorrhage. The aim of this report is to describe the current transfusion practices in Europe for patients with major hemorrhage and explore the need for new or modified blood products to ensure prehospital and in‐hospital blood supply. Study Design and Method: The European Blood Alliance (EBA) Working Group on Innovation and New Blood Products' subgroup on major hemorrhage performed a survey among the EBA member states. Results: The response rate was 58% (17 responses from 15 of the 26 EBA member states). Of these, sixteen (94%) provide massive transfusion packages (MTPs) with balanced ratio of red blood cells and plasma. Seven of the respondents included platelets from the start of treatment. Eleven (65%) provide prehospital blood products, mainly red cell concentrates or dried and/or thawed plasma with 5 days of extended storage. Two countries provide prehospital whole blood. Twelve respondents (71%) saw a need for implementation of new or modified blood components in their institution. The top three priorities were whole blood (12 of 12, 100%), dried plasma (8 of 12, 67%), and cold‐stored platelets (7 of 12, 58%). Discussion: Current national guidelines for use of blood products in patients with major hemorrhage in Europe agree on the use of balanced transfusion, however the timing and source of platelets differ. Blood products for prehospital transfusion are available in several European countries. An interest in new or modified blood products for patients with major hemorrhage was observed, especially for whole blood. [ABSTRACT FROM AUTHOR]

Background: Prehospital anesthesia may lead to circulatory collapse after severe hemorrhage. It is possible that permissive hypoventilation, refraining from tracheal intubation and accepting spontaneous ventilation, decreases this risk, but it is not known if oxygen delivery can be maintained. We investigated the feasibility of permissive hypoventilation after class III hemorrhage and whole blood resuscitation in three prehospital phases: 15 min on‐scene, 30 min whole blood resuscitation, and 45 min after. Study Design and Methods: 19 crossbred swine, mean weight 58.5 kg, were anesthetized with ketamine/midazolam and hemorrhaged to a mean (SD) 1298 (220) mL (33%) and randomized to permissive hypoventilation (n = 9) or positive pressure ventilation with FiO2 21% (n = 10). Results: In permissive hypoventilation versus positive pressure ventilation, indexed oxygen delivery (DO2I) decreased to mean (SD) 4.73 (1.06) versus 3.70 (1.13) mL min−1 kg−1 after hemorrhage and increased to 8.62 (2.09) versus 6.70 (1.56) mL min−1 kg−1 at completion of resuscitation. DO2I, indexed oxygen consumption (VO2I), and arterial saturation (SaO2) did not differ. Permissive hypoventilation increased the respiratory rate and increased pCO2. Positive pressure ventilation did not deteriorate circulation. Cardiac index (CI), systolic arterial pressure (SAP), hemoglobin (Hb), and heart rate did not differ. Discussion: Permissive hypoventilation and positive pressure ventilation were equally effective to maintain oxygen delivery in all phases. A respiratory rate of 40 was feasible, showing no signs of respiratory fatigue for 90 min, indicating that whole blood resuscitation may be prioritized in select patients with severe hemorrhage and spontaneous breathing. [ABSTRACT FROM AUTHOR]

Background: Hypofibrinogenemia is an important risk factor for poor outcomes in children with severe bleeding. There is a paucity of data on the impact of cryoprecipitate transfusion on outcomes in pediatric patients with life‐threatening hemorrhage (LTH). Study Design and Methods: This secondary analysis of a multicenter prospective observational study of children with LTH investigated subjects who were categorized by receipt of cryoprecipitate during their resuscitation and according to the etiology of their bleeding: trauma, operative, and medical. Bivariate analysis was performed to identify variables associated with 6‐h, 24‐h, and 28‐day mortality. Cox Hazard regression models were generated to adjust for potential confounders. Results: Cryoprecipitate was transfused to 33.9% (152/449) of children during LTH. The median (Interquartile range) time to cryoprecipitate administration was 108 (47–212) minutes. Children in the cryoprecipitate group were younger, more often female, with higher BMI and pre‐LTH PRISM score and lower platelet counts. After adjusting for PRISM score, bleeding etiology, age, sex, RBC volume, platelet volume, antifibrinolytic use and cardiac arrest, cryoprecipitate administration was independently associated with lower 6‐h mortality, Hazard Ratio (95% CI), 0.41 (0.19–0.89), (p = 0.02) and 24‐h mortality, Hazard Ratio (95% CI), 0.46 (0.24–0.89), (p = 0.02). Conclusion: Cryoprecipitate transfusion to children with LTH was associated with reduced early mortality. A prospective randomized trial is needed to determine if cryoprecipitate can improve outcomes in children with LTH. [ABSTRACT FROM AUTHOR]

BackgroundThere have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost-effectiveness ratio, when estimated using patients' age-specific life expectancy and cost of care during the 30-day PROPPR trial period.Study design and methodsInternational Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments.ResultsThe 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained.ConclusionThe 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost-effective strategy for increasing hemostasis and decreasing trauma deaths.

Background: Fibrinogen thromboelastometry (FIBTEM) test is clinically used for rotational thromboelastometry as a surrogate measure of fibrinogen. Elevated fibrinogen might confer protection against bleeding after major surgery. This single-center study was conducted to assess any relationship between baseline FIBTEM value and exposure to allogeneic transfusion in patients undergoing coronary artery bypass grafting (CABG).Study Design and Methods: Data were obtained retrospectively from local FIBTEM data and the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database between 2016 and 2019. Preoperative FIBTEM 10-min amplitude (A10) was categorized as low (≤ 18 mm), intermediate (19-23 mm), or high (≥24 mm). The primary outcome was any transfusion during the hospitalization, including red blood cells (RBCs), platelets, plasma, and cryoprecipitate. A multivariable regression model was used to adjust for confounders and calculate an odds ratio (OR) for any transfusion.Results: The high FIBTEM group included more female and African-American patients, as well as urgent surgery. The STS predicted risks of morbidity and mortality were greater, and anemia was most prevalent with high FIBTEM. Unadjusted blood transfusion rates were increased with high FIBTEM due to RBC transfusion, but non-RBC transfusion was highest with low FIBTEM. After adjustments, a lower OR for transfusion was associated with high FIBTEM (0.426; 95% confidence interval, 0.199-0.914) compared to low FIBTEM.Conclusion: The high FIBTEM group frequently presented with anemia and comorbidities, and received more RBCs but not non-RBC products. Postoperative blood loss was less with high FIBTEM, and after adjustments, it conferred protection against any transfusion. [ABSTRACT FROM AUTHOR]

Background: Pathogen reduction technology (PRT) effectively mitigates bacterial contamination in platelets but is more likely to produce low yield units. Although low dose transfusion using conventional platelets has not been associated with increased bleeding, these findings have not been reproduced with PRT-treated platelets.Study Design and Methods: Platelet transfusions in a tertiary adult hospital were retrospectively reviewed. Comparisons were made between PRT-treated regular (PRT-PR) and low (PRT-PL) yield platelets. Outcomes examined included the number of platelets and RBCs transfused, transfusion-free interval, and corrected count increment (CCI). Subgroup analyses were also performed on hematology-oncology inpatients and outpatients, as well as non-hematology-oncology patients.Results: Platelet utilization per patient remained mostly unchanged (mean 2.9-4.3 units per patient per month) even when the frequency of PRT-PL transfusion increased. Among 1402 patients examined, the number of platelets and RBCs transfused was not significantly different between patients first transfused with PRT-PR versus PRT-PL (mean number of platelet units = 2.8 vs. 3.1, p = 0.38; mean number of RBC units = 4.8 vs. 4.3, p = 0.93). Among 10,257 platelet transfusions examined, the transfusion-free interval (hazard ratio = 1.05, 95% confidence interval 1.00-1.10) and CCI (10.2 vs. 11.0, p = 0.70) were comparable between PRT-PR and PRT-PL units. Similar findings were observed in all subgroups, except for shortened transfusion-free intervals among hematology-oncology inpatients.Conclusion: PRT-PR and PRT-PL units may be used in an equivalent manner to maintain an adequate platelet inventory, since there was only a minor difference in time between transfusions. [ABSTRACT FROM AUTHOR]

Background: Multiple reports suggest that cold-stored low-titer type O whole blood (LTOWB) is becoming a preferred transfusion product for resuscitating massive hemorrhage across trauma, obstetrical, and pediatric services. However, we know of no reports of using this product for emergency transfusion of newborn infants after acute severe hemorrhage.Case Report: We report our experience with emergency transfusion of re-warmed LTOWB using a fluid warmer for the resuscitation of a hypotensive 25-week gestation neonate following acute and severe placental abruption. The transfusion was tolerated well, without evidence of hemolysis or other complications.Conclusions: This is the first report of which we are aware of transfusing warmed LTOWB to a preterm neonate. Our positive experience leads us to speculate that this product could have a role for neonates following acute severe blood loss. [ABSTRACT FROM AUTHOR]

Background: There is an increasing literature demonstrating the benefits of prehospital and early in‐hospital transfusions. RhD‐positive products might only be available during these phases, which could pose consequences for future pregnancies if D‐alloimmunization occurs. This survey measured the willingness of females to accept urgent but incompatible transfusions in light of the potential for future pregnancy complications. Methods: A survey was designed to assess the willingness of females ≥18 years of age to accept urgent incompatible transfusions when different absolute risk reductions in maternal mortality were presented along with a static rate of 0.3%–4.0% risk of harm to future pregnancies. The survey was sent electronically to women who are part of the Washington University Research Enhancement Core database. Results: A total of 4896 delivered survey email invitations were distributed and 325 (6.6%) responses were received; 16 responses were excluded leaving 309 responses for analysis. Most of the responding women were White, college‐educated, and lived in Missouri. At least 90% of the respondents would accept an urgent incompatible transfusion when the absolute risk reduction in maternal mortality was ≥4%. Women without a college degree, who lived in Illinois, who were not able to have children appeared to be less willing than their counterparts to receive an incompatible transfusion when the absolute risk reduction in maternal mortality was low. Conclusion: This survey demonstrated that adult women are highly likely to be open to accept urgent incompatible blood transfusions during a bleeding emergency when the absolute risk reduction in maternal mortality was ≥4%. [ABSTRACT FROM AUTHOR]

Background: We evaluated patient outcomes after early, small volume red blood cell (RBC) transfusion in the setting of presumed hemorrhagic shock. We hypothesized that transfusion with even small amounts of blood would be associated with more complications. Study design and methods: Retrospective review of trauma patients admitted to a Level 1 trauma center between 2016–2021. Patients predicted to require massive transfusion who survived ≥72 h were categorized according to units of RBCs transfused in the first 24 h. A Cox regression model stratified by dichotomized ISS and adjusted for SBP <90 mm Hg and pulse >120 bpm on arrival was used to estimate hazard ratios (HRs) for outcomes of interest. Results: A total of 3121 (24%) received RBC transfusion within the first 24 h. Massive transfusion protocol (MTP) was activated in 38% (1188/3121): 17% received no RBCs, 27.4% 1–3 units, 32.4% 4–9 units, and 22.7% ≥10 units. Mean ISS increased with each category of RBC transfusion. There was no difference in the risk of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), infection, cardiac arrest, venous thromboembolism or stroke for patients receiving 1–3 units compared to the non‐transfused group or 4–9 units group (p > 0.05). Compared to those receiving ≥10 units, the 1–3 units group had a significantly lower risk of AKI, ARDS, and cardiac arrest. Discussion: Early empiric RBC transfusion for presumed hemorrhagic shock may subject patients to potential over‐transfusion and end‐organ damage. Among patients meeting clinical triggers for MTP, 1–3 units of allogeneic RBCs is not associated with worse outcomes. [ABSTRACT FROM AUTHOR]

Tranexamic acid (TXA) is a popular antifibrinolytic drug widely used in hemorrhagic trauma patients and cardiovascular, orthopedic, and gynecological surgical patients. TXA binds plasminogen and prevents its maturation to the fibrinolytic enzyme plasmin. A number of studies have demonstrated the broad life-saving effects of TXA in trauma, superior to those of other antifibrinolytic agents. Besides preventing fibrinolysis and blood loss, TXA has been reported to suppress posttraumatic inflammation and edema. Although the efficiency of TXA transcends simple inhibition of fibrinolysis, little is known about its mechanisms of action besides the suppression of plasmin maturation. Understanding the broader effects of TXA at the cell, organ, and organism levels are required to elucidate its potential mechanisms of action transcending antifibrinolytic activity. In this article, we provide a brief review of the current clinical use of TXA and then focus on the effects of TXA beyond antifibrinolytics such as its anti-inflammatory activity, protection of the endothelial and epithelial monolayers, stimulation of mitochondrial respiration, and suppression of melanogenesis. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures.Study Design and Methods: Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs).Results: Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Compared with plasma, patients receiving Cofact probably have a higher rate of international normalized ratio (INR) correction (risk difference [RD] 499 more per 1000 patients, 95% confidence interval [CI], 176-761, low certainty[LC]); higher reversal of bleeding (323 more per 1000 patients, 11-344 more, LC); and fewer transfusion requirements (0.96 fewer units, 1.65-0.27 fewer, LC). Patients receiving Beriplex/KCentra probably have a higher rate of INR correction (476 more per 1000 patients, 332-609 more, LC); higher reversal of bleeding (127 more per 1000 patients, 43 fewer to 236 more); and similar transfusion requirements (0.01 fewer units, 0.31 fewer to 0.28 more, high/moderate certainty). Patients receiving Octaplex probably have a higher rate of INR correction (RD 579 more per 1000 patients, 189-825 more, LC).Conclusions: PCCs probably provide an advantage in INR reversal compared to plasma. There was no added risk of adverse events with PCCs. [ABSTRACT FROM AUTHOR]

Objective: To report maternal outcomes in a cohort of women who received autotransfusion of vaginally shed blood and to describe the feasibility of blood collection and cell salvage processing at the time of vaginal hemorrhage. Study Design and Methods: We conducted a retrospective case series of patients who received autotransfusion of vaginally shed blood at the time of obstetric hemorrhage from January 2014 to August 2020. Maternal data and cell salvage utilization characteristics were abstracted from the electronic medical record. Results: Sixty‐four cases were identified in which autotransfusion of vaginally shed blood occurred during an obstetric hemorrhage. Median quantitative blood loss was 2175 ml (interquartile range 1500–2250 ml) with 89% of cases having a blood loss greater than 1000 ml. Patients on average received approximately 1.3 units of autologous blood product (384 ml, interquartile range 244–520 ml) and no direct adverse events were observed during transfusion. We observed heterogeneity in autologous blood volume across all values of quantitative blood loss. The need for allogenic blood transfusion was common and occurred in 72% of all cases (N = 46). There were no documented cases of maternal sepsis or severe infectious morbidity. Conclusion: In 64 cases where autotransfusion of vaginally shed blood occurred, autotransfusion was well tolerated. Heterogeneity in autologous blood volume collection likely represents the lack of standardized protocols for blood collection in the delivery room. Autotransfusion of vaginally shed blood is a feasible and reasonable technique to employ during severe obstetric hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Transfusion is very common in the intensive care unit (ICU), but practice is highly variable, as has recently been shown in non‐bleeding critically ill patients practices survey. Bleeding patients in ICU require different blood products across a range of specific patient categories. We hypothesize that a large variety in transfusion practice exists in bleeding patients. Study design and methods: An international online survey was performed among physicians working in the ICU. Transfusion practice in massively and non‐massively bleeding patients was examined, including transfusion ratios, thresholds, and the presence of transfusion guidelines. Results: Six hundred eleven respondents filled in the survey of which 401 could be analyzed, representing 64 countries. Among the respondents, 52% had a massive transfusion protocol (MTP) available at their ICU. In massively bleeding patients, 46% of the respondents used fixed transfusion component ratios. Of those who used fixed blood ratios, the 1:1:1 ratio (red blood cell [RBC] concentrates: plasma: platelet concentrates) was most commonly used (33%). The presence of an MTP was associated with a more frequent use of fixed ratios (p <.001). For RBC transfusion in the general non‐massively bleeding ICU population, a hemoglobin (Hb) threshold of 7.0[7.0–7.3] g/dl was reported. In the general ICU population, a platelet count threshold of 50[26–50] × 109/L was applied. Discussion Half of the centers had no massive transfusion protocol available. Transfusion practice in massively bleeding critically ill patients is highly variable and driven by the presence of an MTP. In the general non‐massively bleeding ICU population restrictive transfusion triggers were chosen. [ABSTRACT FROM AUTHOR]

Background: Although therapeutic plasma exchange (TPE) is associated with hemostatic abnormalities, its impact on bleeding outcomes is unknown. Therefore, the main study objective was to determine bleeding outcomes of inpatients treated with TPE. Study Design and Methods: In a cross‐sectional analysis of the National Inpatient Sample (NIS), discharges were identified with 10 common TPE‐treated conditions. A 1:3 propensity‐matched analysis of TPE‐ to non‐TPE‐treated discharges was performed. The primary outcome was major bleeding and secondary outcomes were packed red blood cell (PRBC) transfusion, mortality, disposition, hospital length of stay (LOS), and charges. Multivariable regression analyses were used to examine the association between TPE and study outcomes. Results: The study population was 15,964 discharges, of which 3991 were TPE‐ treated. The prevalence of major bleeding was low (5.4%). When compared to non‐TPE discharges, TPE had a significant and positive association with major bleeding (OR = 1.37, 95% CI: 1.16–1.63, p =.0003). TPE was also associated with PRBC transfusion (OR = 1.66, 95% CI: 1.42–1.94, p <.0001), in‐hospital mortality (OR = 1.45, 95% CI: 1.10–1.90, p =.0008), hospital length of stay (12.45 [95% CI: 11.95–12.97] vs. 7.38 [95% CI: 7.12–7.65] days, p <.0001) and total charges, ($125,123 [95% CI: $119,220–$131,317] vs. $61,953 [95% CI: $59,391–$64,625], p <.0001), and disposition to non‐self‐care (OR = 1.29, 95% CI: 1.19–1.39, p <.0001). Discussion: The use of TPE in the inpatient setting is positively associated with bleeding; however, with low prevalence. Future studies should address risk factors that predispose patients to TPE‐associated bleeding. [ABSTRACT FROM AUTHOR]

Background: Early plasma transfusion is life-saving for bleeding trauma patients. Freeze-dried plasma (FDP) provides unique formulation advantages for infusion in the prehospital setting. We describe characterization and clinical safety data of the first, next-generation FDP stored in plastic bags with rapid reconstitution.Study Design and Methods: Coagulation and chemistry parameters on 155 pairs of fresh frozen plasma (FFP) and their derivative FDP units were compared. Next, a first-in-human, dose-escalation safety evaluation of FDP, involving 24 healthy volunteers who donated either whole blood or apheresis plasma to create autologous FDP, was performed in three dose cohorts (270, 540, and 810 ml) and adverse events (AEs) were monitored. Cohort 3 was randomized, double-blind with a cross-over arm that compared FDP versus FFP using descriptive analysis for AEs, coagulation, hematology, and chemistry parameters.Results: FDP coagulation factors, clotting times, and product quality (pH, total protein, and osmolality) post-lyophilization were preserved. FDP infusions, of up to 810 ml per subject, were found to be safe and with no serious AEs (SAEs) related to FDP. The average time to reconstitute FDP was 67 s (range: 43-106). No differences in coagulation parameters or thrombin activation were detected in subjects infused with 810 ml of FDP compared with FFP.Conclusion: This first next-generation FDP product preserves the potency and safety of FFP in a novel rugged, compressible, plastic container, for rapid transfusion, allowing rapid access to plasma in resuscitation protocols for therapy in acute traumatic hemorrhage. [ABSTRACT FROM AUTHOR]

Background: We previously reported fetomaternal hemorrhage (FMH) in 1/9160 births, and only one neonatal death from FMH among 219,853 births. Recent reports indicate FMH is not uncommon among stillbirths. Consequently, we speculated we were missing cases among early neonatal deaths. We began a new FMH initiative to determine the current incidence. Methods: We analyzed births from 2011 to 2020 where FMH was diagnosed. We also evaluated potential cases among neonates receiving an emergent transfusion just after birth, whose mothers were not tested for FMH. Results: Among 297,403 births, 1375 mothers were tested for FMH (1/216 births). Fourteen percent tested positive (1/1599 births). Of those, we found 25 with clinical and laboratory evidence of FMH adversely affecting the neonate. Twenty‐one received one or more emergency transfusions on the day of birth; all but two lived. We found 17 others who received an emergency transfusion on the day of birth where FMH was not tested for, but was likely; eight of those died. The 42 severe (proven + probable) cases equate to 1/7081 births. We judged that 10 of the 42 had an acute FMH, and in the others it likely had more than a day before birth. Conclusions: We estimate that we fail to diagnose >40% of our severe FMH cases. Needed improvements include (1) education to request maternal FMH testing when neonates are born anemic, (2) education on false‐negative FMH tests, and (3) improved FMH communications between neonatology, obstetrics, and blood bank. [ABSTRACT FROM AUTHOR]

Background: Essential thrombocythemia (ET) is associated with increased risk of bleeding secondary to acquired von Willebrand syndrome (AVWS). Bleeding in ET requires urgent platelet reduction by cytoreductive therapy such as hydroxyurea or thrombocytapheresis. We report on the efficacy and safety of thrombocytapheresis in managing AVWS in a patient with ET and multivisceral transplantation. Case report: The patient was a 51‐year‐old female who underwent multivisceral transplantation. Her postoperative course was complicated by bleeding from oral cavity, IV lines, gastrointestinal and upper respiratory tracts as well as vaginal bleeding, which coincided with ET flare with a platelet count of 1512 × 109/L. Coagulation studies including von Willebrand factor (vWF) antigen and activity, vWF propeptide antigen, and vWF multimer analysis were consistent with AVWS. Hydroxyurea was initiated. However, due to major bleeding, rapidly increasing platelet count, and uncertainty of response to hydroxyurea being given through the enteral tube, thrombocytapheresis was initiated for rapid platelet reduction. The patient tolerated the procedure well. Platelet count was reduced from 1636 × 109/L to 275 × 109/L with rapid cessation of bleeding. The patient's condition stabilized over the next few days; however, bleeding recurred with increasing platelet count, which required a second thrombocytapheresis 8 days after the first one. The patient was maintained on hydroxyurea 500 mg twice/day. At 11‐month follow‐up, she had a normal platelet count and no recurrence of bleeding. Discussion: Thrombocytapheresis is safe and efficient in managing postoperative bleeding due to ET/AVWS in solid organ transplant patients. The procedure can be an adjunct to bridging therapy before response to hydroxyurea is achieved. [ABSTRACT FROM AUTHOR]

Background: Prophylactic platelet transfusions prevent bleeding in hemato‐oncology patients, but it is unclear how any benefit varies between patients. Our aim was to assess if patients with different baseline risks for bleeding benefit differently from a prophylactic platelet transfusion strategy. Study design and methods: Using the data from the randomized controlled TOPPS trial (Trial of Platelet Prophylaxis), we developed a prediction model for World Health Organization grades 2, 3, and 4 bleeding risk (defined as at least one bleeding episode in a 30 days period) and grouped patients in four risk‐quartiles based on this predicted baseline risk. Predictors in the model were baseline platelet count, age, diagnosis, disease modifying treatment, disease status, previous stem cell transplantation, and the randomization arm. Results: The model had a c‐statistic of 0.58 (95% confidence interval [CI] 0.54–0.64). There was little variation in predicted risks (quartiles 46%, 47%, and 51%), but prophylactic platelet transfusions gave a risk reduction in all risk quartiles. The absolute risk difference (ARD) was 3.4% (CI −12.2 to 18.9) in the lowest risk quartile (quartile 1), 7.4% (95% CI −8.4 to 23.3) in quartile 2, 6.8% (95% CI −9.1 to 22.9) in quartile 3, and 12.8% (CI −3.1 to 28.7) in the highest risk quartile (quartile 4). Conclusion: In our study, generally accepted bleeding risk predictors had limited predictive power (expressed by the low c‐statistic), and, given the wide confidence intervals of predicted ARD, could not aid in identifying subgroups of patients who might benefit more (or less) from prophylactic platelet transfusion. [ABSTRACT FROM AUTHOR]

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP. [ABSTRACT FROM AUTHOR]

Background: Whole blood therapy-which contains the ideal balance of components, and particularly fresh whole blood-has been shown to be beneficial in adult trauma. It remains unclear whether there is potential benefit in the pediatric population.Study Design and Methods: This is a secondary analysis of previously published data analyzing pediatric casualties undergoing massive transfusion in the Department of Defense Trauma Registry. Pediatric patients with traumatic injury who were transfused at least one blood product were included in the analysis. We compared children who received component therapy exclusively to those who received any amount of warm fresh whole blood.Results: Of the 3439 pediatric casualties within our dataset, 1244 were transfused at least one blood product within the first 24 h. There were 848 patients without severe head injury. Within this cohort, 23 children received warm fresh whole blood overall, 20 of whom did not have severe head injury. In an adjusted analysis, the odds ratio (95% confidence interval [CI]) for survival for warm fresh whole blood recipients was 2.86 (0.40-20.45). After removing children with severe brain injury, there was an independent association with improved survival for warm fresh whole blood recipients with an odds ratio (95% CI) of 58.63 (2.70-1272.67).Discussion: Our data suggest that warm fresh whole blood may be associated with improved survival in children without severe head injury. Larger prospective studies are needed to assess the efficacy and safety of whole blood in children with severe traumatic bleeding. [ABSTRACT FROM AUTHOR]

Introduction: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC).Methods: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC).Results: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC.Conclusions: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI. [ABSTRACT FROM AUTHOR]

Background: Civilian and military guidelines recommend early balanced transfusion to patients with life-threatening bleeding. Low titer group O whole blood was introduced as the primary blood product for resuscitation of massive hemorrhage at Haukeland University Hospital, Bergen, Norway, in December 2017. In this report, we describe the whole blood program and present results from the first years of routine use.Study Design and Methods: Patients who received whole blood from December 2017 to April 2020 were included in our quality registry for massive transfusions. Post-transfusion blood samples were collected to analyze isohemagglutinin (anti-A/-B) and hemolysis markers. Administration of other blood products, transfusion reactions, and patient survival (days 1 and 30) were recorded. User experiences were surveyed for both clinical and laboratory staff.Results: Two hundred and five patients (64% male and 36% female) received 836 units in 226 transfusion episodes. Patients received a mean of 3.7 units (range 1-35) in each transfusion episode. The main indications for transfusion were trauma (26%), gastrointestinal (22%), cardiothoracic/vascular (18%), surgical (18%), obstetric (11%), and medical (5%) bleeding. There was no difference in survival between patients with blood type O when compared with non-group O. Haptoglobin level was lower in the transfusion episodes for non-O group patients, however no clinical hemolysis was reported. No patients had conclusive transfusion-associated adverse events. Both clinical and laboratory staff preferred whole blood to component therapy for massive transfusion.Discussion: The experience from Haukeland University Hospital indicates that whole blood is feasible, safe, and effective for in-hospital treatment of bleeding. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Keywords: female of childbearing potential; hemorrhage; red blood cell; Rh immunoglobulin; RhD; transfusion; whole blood EN female of childbearing potential hemorrhage red blood cell Rh immunoglobulin RhD transfusion whole blood S326 S332 7 07/19/21 20210702 NES 210702 Abbreviations DNA deoxyribonucleic acid HLA human leukocyte antigen ICU intensive care unit IV intravenous LTOWB low titer group O whole blood RBC red blood cells RhIg Rh immune globulin INTRODUCTION There is mounting evidence demonstrating that survival is improved when transfusions are provided early in the resuscitation of traumatically injured patients. Some centers have a policy of neither attempting to hemolyze >1 RhD-positive RBC/LTOWB unit nor performing exchange transfusions when >1 RhD-positive RBC/LTOWB units have been transfused to an RhD-negative female of childbearing potential. So, in the situation where an RhD-negative female of childbearing potential received >1 RhD-positive RBC/LTOWB, one means of preventing RhD alloimmunization would be to perform an automated RBC exchange procedure using RhD-negative RBCs. Mixed feelings about mixed-field agglutination: A pathway for managing females of childbearing potential of unknown RhD-type who are transfused RhD-positive and RhD-negative red blood cells during emergency hemorrhage resuscitation. [Extracted from the article]

Background: In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC.Methods: Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy.Results: In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy.Conclusions: In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates. [ABSTRACT FROM AUTHOR]

Background: Multiple thresholds are defined to identify patients at risk of death from hemorrhage, including massive transfusion (MT), critical administration threshold (CAT), and resuscitation intensity (RI). All fail to account for the use of whole blood (WB). We hypothesized that a definition including WB transfusion would better predict early mortality following trauma.Methods: This is a retrospective review of all trauma patients with activation of the MT protocol from December 2018 to February 2020. Combinations of WB, RBCs, and fresh frozen plasma (FFP) units transfused during the initial hour of resuscitation were compared using receiver operating characteristic and area under the receiver curve (AUC) for 3- and 6-h mortality. WB massive transfusion (WB MT) score was defined as the sum of each unit RBC plus three times each unit of WB transfused within the first hour of resuscitation.Results: There were 235 patients eligible for analysis with 60 resuscitated using ≥1 unit of WB. Overall, 27 and 29 patients died in the first 3 and 6 h, respectively. WB MT ≥7 had the greatest 3-h and 6-h mortality AUC values (0.78 and 0.79, respectively) when compared to MT, CAT, RI4+, and other attempted definitions using units of WB, RBC, and FFP. Compared to WB MT-, WB MT+ patients died at significantly higher rates at 3 h (28.9% vs. 3.1%, p < .001), 24 h (35.5% vs. 5.7%, p < .001), and 28 days (42.1% vs. 11.9%, p < .001).Conclusion: WB MT is the first measure of massive resuscitation to incorporate WB and better identifies early mortality than other definitions. [ABSTRACT FROM AUTHOR]

Background: Platelet transfusion is challenging in emergency medicine because of short platelet shelf life and stringent storage conditions. Platelet‐derived extracellular vesicles (PEV) exhibit platelet‐like properties. A plasma generated from expired platelet units rich in procoagulant PEV may be able to combine the benefits of plasma and platelets for resuscitation while increasing shelf life and utilizing an otherwise wasted resource. Study design and methods: Freeze–thaw cycling of platelet‐rich plasma (PRP) followed by centrifugation to remove platelet remnants was utilized to generate platelet‐enhanced plasma (PEP). An in vitro model of dilutional coagulopathy was also designed and used to test PEP. Rotational thromboelastometry and calibrated automated thrombography were used to assess clotting and extracellular vesicles (EV) procoagulant activity. Capture arrays were used to specifically measure EV subpopulations of interest (ExoView™, NanoView Biosciences). Captured vesicles were quantified and labeled with Annexin‐V‐FITC, CD41‐PE, and CD63‐AF647. Platelet alpha granule content (platelet‐derived growth factor AB, soluble P‐selectin, vascular endothelial growth factor A, and neutrophil activating peptide 2‐chemokine (C‐X‐C motif) ligand 7) was measured. Commercially available platelet lysates were also characterized. Results: PEP is highly procoagulant, rich in growth factors, exhibits enhanced thrombin generation, and restores hemostasis within an in vitro model of dilutional coagulopathy. The predominant vesicle population were PEV with 7.0 × 109 CD41+PS+ EV/ml compared to 4.7 × 107 CD41+PS+ EV/ml in platelet‐free plasma (p =.0079). Commercial lysates show impaired but rescuable clotting. Discussion: PEP is a unique candidate resuscitation fluid containing high PEV concentration with preliminary evidence, indicating a potential for upscaling the approach using platelet concentrates. Commercial lysate manufacturer workflows may be suitable for this, but further optimization and characterization of PEP is required. [ABSTRACT FROM AUTHOR]

Background: Immune thrombocytopenia (ITP) is an acquired disease characterized by thrombocytopenia secondary to autoantibodies against platelets. Here, we report the clinical characteristics of coronavirus disease 2019 (COVID‐19)‐induced ITP cases. Study Design and Methods: We retrospectively reviewed 3255 COVID‐19 patients. COVID‐19‐induced ITP was diagnosed after excluding possible common causes. Bleeding severity was assessed based on the modified World Health Organization (WHO) bleeding severity score. Results: We identified 11 (0.34%) patients with COVID‐19‐induced ITP. Of all patients, 63.6% were males and the median age was 63 years. The median time from COVID‐19 diagnosis to the onset of ITP was 10 days. Bleeding observed in 63.6% of the patients. Clinically significant bleeding (WHO Grade 3) occurred in single patient who required blood transfusion. Standard treatment with glucocorticoids and intravenous immunoglobulin (IVIG) was effective in achieving excellent response in most cases. Of all patients, complete response and response to treatment were achieved in 45.5% and 27.3% patients, respectively. The median time to ITP recovery was 4 days. Eltrombopag was used in three patients who relapsed. Four patients required mechanical ventilation, and none of them survived secondary to hypoxic respiratory failure. Conclusion: ITP secondary to COVID‐19 usually presents after the first week of symptoms beginning. Most of our patients had WHO Grade 1–2 bleeding scores. Standard treatment with glucocorticoids and IVIG is effective in achieving an excellent response. The safety of eltrombopag is not very well established in COVID‐19 patients, and additional studies are needed for a better safety profile. [ABSTRACT FROM AUTHOR]

See article on page 1710–1720, in this issue [ABSTRACT FROM AUTHOR]

Key Ideas: Degree of thrombocytopenia is not a predictor of bleeding risk in neonates, yet most platelet transfusions are given prophylactically in non‐bleeding premature infants.Recent data support a lower platelet transfusion threshold of 25 × 109/L in non‐bleeding premature neonates and indicate that higher transfusion thresholds may be associated with harm including increased risk of death and bleeding.The mechanism of increased adverse events with higher platelet transfusion threshold is unknown, but considerations include adult platelets disrupting the neonatal hemostatic balance of hypoactive platelets in a hypercoagulable and fragile environment and having a pro‐inflammatory effect. [ABSTRACT FROM AUTHOR]

Background: Platelet (PLT) transfusions are an essential treatment for bleeding disorders. However, immunologic complications can occur, including alloantibody production against Class I HLA molecules. The principal source of HLA molecules in PLT concentrates (PCs) is the PLTs themselves. However, extracellular microparticles (MPs) present in PCs may express HLA molecules.Study Design and Methods: We used nanoscale flow cytometry to explore the expression of HLA-A2, HLA-B7, and HLA-B57 on the surface of cells, PLT-derived MPs (PMPs), lymphocyte-derived MPs (LMPs), and monocyte-derived MPs (MMPs) present in PCs. Expression was studied during 7 days of storage.Results: Platelets were not the only source of HLA molecules in PCs. HLA molecules were present on PMPs, LMPs, and MMPs. The level of HLA Class I molecule expression varied between haplotypes and MPs of different origins and during storage.Conclusion: Platelets or residual cells remaining after leukoreduction are not the only source of HLA Class I molecules in PCs, highlighting the contribution of MPs to alloimmunization mechanisms. These data may be relevant for the development of new transfusion guidelines. [ABSTRACT FROM AUTHOR]

We report a case of a 56‐year‐old woman with a history of idiopathic thrombocytopenic purpura (ITP) following splenectomy on mycophenolate mofetil (MMF), who developed moderate bleeding after stopping MMF. Her laboratory testing suggested the presence of an abnormal circulating heparin‐like anticoagulant with demonstrable anti‐Xa activity. She was initially treated with antifibrinolytic therapy and was subsequently started on MMF alongside intravenous immunoglobulin, which significantly improved her bleeding symptoms. The presence of abnormal circulating heparin‐like anticoagulants is a rare cause of coagulopathy. Few cases exist in the literature, with nearly all occurring in the setting of hematologic or solid‐organ malignancy. The mechanism by which these endogenous anticoagulants develop is unclear. Clinical manifestations range from mild bleeding and bruising to life‐threatening hemorrhage refractory to conventional therapy. Diagnosis of a heparin‐like anticoagulant is based on coagulation testing as well as exclusion of other exogenous anticoagulants, acquired inhibitors, and/or factor deficiencies. [ABSTRACT FROM AUTHOR]

Link to: Article TRF16126 [ABSTRACT FROM AUTHOR]