Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667468.

Impact of systematic variations in hematocrit and platelet count on thrombelastometry tissue factor activated assay parameters.

BACKGROUND: Thromboelastogram testing is increasingly being used to manage patients with massive bleeding. An earlier study found that the test results were influenced by the hematocrit (Hct) and platelet (PLT) concentrations. This study sought to determine if these factors confounded the results of a different manufacturer's thromboelastography testing. METHODS: Using freshly collected whole blood from volunteers and stored red blood cells (RBC) and plasma, the whole blood was manipulated to achieve different Hct values and PLT concentrations. Each reconstituted whole blood sample was tested in triplicate on the ROTEM Delta device and the ExTEM results were recorded. RESULTS: Many of the ExTEM results varied according to the Hct and PLT concentration. In particular, the ExTEM clot formation time (CFT) was abnormally long when the Hct was 45% and the PLT concentration was ≤75 × 109/L, normalizing only when the PLT count was ≥100 × 109/L. CFT samples with Hct 25% and 35% were also abnormal with low PLT concentrations but normalized at lower PLT concentrations compared to the Hct 45% samples. The ExTEM angle also demonstrated abnormal results when the Hct was 45% and the PLT concentration was ≤50 × 109/L. The ExTEM A10 and maximum clot firmness (MCF) tests tended to also be abnormal when the Hct was between 25% and 45% and the platelet concentrations were below 75 × 109/L. CONCLUSION: While thromboelastogram testing is gaining popularity for managing bleeding patients, clinicians should be aware of these confounding factors when making transfusion decisions based on their results.

Effect of major trauma on the expected number of births in Finnish women: A nationwide population-based public data and register analysis.

BACKGROUND: The effect of major trauma on subsequent fertility is poorly described. If women have lower fertility after trauma, they would have a lower risk of anti-D mediated hemolytic disease of the fetus and newborn in a future pregnancy following the transfusion of RhD-positive blood to RhD-negative women during their resuscitation. STUDY DESIGN AND METHODS: Data was obtained from the Care Register for Health Care, National Medical Birth Register, and open access data from Statistic Finland to evaluate the effect of major trauma (traumatic brain injuries, spine, pelvic, hip/thigh fractures) on the age-specific number of births during years 1998-2018. The total number of births before a specific maternal age for different trauma populations was calculated and these were compared to the corresponding number of births in the general population. RESULTS: There were 50,923 injured women in this study. All injured women, including when analyzed by the nature of their injury, demonstrated lower expected numbers of births starting at approximately 28 years of age compared to the general population of women in Finland. At age 49, the expected number of births in the general population was approximately 1.8, whereas for all injured women 0.6, women with TBIs and spine fractures 0.6, women with pelvic fractures 0.5, and women with hip or thigh fractures 0.3. DISCUSSION: Injured women are predicted to have lower fertility rates compared to the general population of Finnish women. The lower fertility rate should be considered when planning a blood product resuscitation strategy for injured women.

Survey of policies at US hospitals on the selection of RhD type of low-titer O whole blood for use in trauma resuscitation.

BACKGROUND: Low-titer group O whole blood (LTOWB) use is increasing due to data suggesting improved outcomes and safety. One barrier to use is low availability of RhD-negative LTOWB. This survey examined US hospital policies regarding the selection of RhD type of blood products in bleeding emergencies. STUDY DESIGN AND METHODS: A web-based survey of blood bank directors was conducted to determine their hospital's RhD-type selection policies for blood issued for massive bleeding. RESULTS: There was a 61% response rate (101/157) and of those responses, 95 were complete. Respondents indicated that 40% (38/95) use only red blood cells (RBCs) and 60% (57/95) use LTOWB. For hospitals that issue LTOWB (N = 57), 67% are supplied only with RhD-positive, 2% only with RhD-negative, and 32% with both RhD-positive and RhD-negative LTOWB. At sites using LTOWB, RhD-negative LTOWB is used exclusively or preferentially more commonly in adult females of childbearing potential (FCP) (46%) and pediatric FCP (55%) than in men (4%) and boys (24%). RhD-positive LTOWB is used exclusively or preferentially more commonly in men (94%) and boys (54%) than in adult FCP (40%) or pediatric FCP (21%). At sites using LTOWB, it is not permitted for adult FCPs at 12%, pediatric FCP at 21.4%, and boys at 17.1%. CONCLUSION: Hospitals prefer issuing RhD-negative LTOWB for females although they are often ineligible to receive RhD-negative LTOWB due to supply constraints. The risk and benefits of LTOWB compared to the rare occurrence of hemolytic disease of the fetus/newborn (HDFN) need further examination in the context of withholding a therapy for females that has the potential for improved outcomes.

Maternal and child life years gained by transfusing low titer group O whole blood in trauma: A computer simulation.

BACKGROUND: Using low titer group O whole blood (LTOWB) is increasingly popular for resuscitating trauma patients. LTOWB is often RhD-positive, which might cause D-alloimmunization and hemolytic disease of the fetus and newborn (HDFN) if transfused to RhD-negative females of childbearing potential (FCP). This simulation determined the number of life years gained by the FCP and her future children if she was resuscitated with LTOWB compared with conventional component therapy (CCT). METHODS: The model simulated 500,000 injured FCPs of each age between 0 and 49 years with LTOWB mortality relative reductions (MRRs) compared with components between 0.1% and 25%. For each surviving FCP, number of life years gained was calculated using her age at injury and average life expectancy for American women. The number of expected future pregnancies for FCPs that did not survive was also based on her age at injury; each future child was assigned the maximum lifespan unless they suffered perinatal mortality or serious neurological events from HDFN. RESULTS: The LTOWB group with an MRR 25% compared with CCT had the largest total life years gained. The point of equivalence for RhD-positive LTOWB compared to CCT, where life years lost due to severe HDFN was equivalent to life years gained due to FCP survival/future childbearing, occurred at an MRR of approximately 0.1%. CONCLUSION: In this model, RhD-positive LTOWB resulted in substantial gains in maternal and child life years compared with CCT. A >0.1% relative mortality reduction from LTOWB offset the life years lost to HDFN mortality and severe neurological events.

Receipt of RhD-positive whole blood for life-threatening bleeding in female children: A survey in alloimmunized mothers regarding minimum acceptable survival benefit relative to risk of maternal alloimmunization to anti-D.

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.

A survey of low titer O whole blood use within the trauma quality improvement program registry.

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.

Novel method for determining when a field-collected donor unit is sufficiently full.

BACKGROUND: Whole blood (WB) collections can occur downrange for immediate administration. An important aspect of these collections is determining when the unit is sufficiently full. This project tested a novel method for determining when a field collection is complete. METHODS: The amount of empty space at the top of WB units, destined to become LTOWB or separated into components, that were collected at blood centers or hospitals was measured by holding a WB unit off the ground and placing the top of a piece of string where the donor tubing entered the bag. The string was marked where it intersected the top of the column of blood in the bag and measured from the top. The WB units were also weighed. RESULTS: A total of 15 different bags, two of which were measured in two different filling volumes, from 15 hospitals or blood centers were measured and weighed. The most commonly used blood bag, Terumo Imuflex SP, had a median string length of 9 mm (range: 2-24 mm) and weighed a median of 565.1 g (range: 524.8-636.7 g). CONCLUSION: Pieces of string can be precut to the appropriate length depending on the type of bag before a mission where field WB collections might be required and a mark placed on the bag before the collection commences to indicate when the unit is full.

Low Titer Group O Whole Blood In Injured Children Requiring Massive Transfusion.

OBJECTIVE: The aim of this study was to assess the survival impact of low-titer group O whole blood (LTOWB) in injured pediatric patients who require massive transfusion. SUMMARY BACKGROUND DATA: Limited data are available regarding the effectiveness of LTOWB in pediatric trauma. METHODS: A prospective observational study of children requiring massive transfusion after injury at UPMC Children's Hospital of Pittsburgh, an urban academic pediatric Level 1 trauma center. Injured children ages 1 to 17 years who received a total of >40 mL/kg of LTOWB and/or conventional components over the 24 hours after admission were included. Patient characteristics, blood product utilization and clinical outcomes were analyzed using Kaplan-Meier survival curves, log rank tests and Cox proportional hazards regression analyses. The primary outcome was 28-day survival. RESULTS: Of patients analyzed, 27 of 80 (33%) received LTOWB as part of their hemostatic resuscitation. The LTOWB group was comparable to the component therapy group on baseline demographic and physiologic parameters except older age, higher body weight, and lower red blood cell and plasma transfusion volumes. After adjusting for age, total blood product volume transfused in 24 hours, admission base deficit, international normalized ratio (INR), and injury severity score (ISS), children who received LTOWB as part of their resuscitation had significantly improved survival at both 72 hours and 28 days post-trauma [adjusted odds ratio (AOR) 0.23, P = 0.009 and AOR 0.41, P = 0.02, respectively]; 6-hour survival was not statistically significant (AOR = 0.51, P = 0.30). Survivors at 28 days in the LTOWB group had reduced hospital LOS, ICU LOS, and ventilator days compared to the CT group. CONCLUSION: Administration of LTOWB during the hemostatic resuscitation of injured children requiring massive transfusion was independently associated with improved 72-hour and 28-day survival.

Whole blood derived and apheresis platelets: Opinions and preferences-the results of a national survey of blood collectors.

INTRODUCTION: Currently greater than 94% of the US platelet supply is collected by apheresis. A survey to determine the attitudes of members of America's Blood Centers (ABC) toward whole blood derived (WBD) platelets was designed in light of current platelet supply issues. METHODS: An on-line survey was distributed to medical directors of the 47 ABC members. RESULTS: Responses were received from 44/47 (94%) ABC members. There were 15/43 (35%) centers that are currently providing WBD platelets. Seventy percent of the respondents agreed or agreed strongly that WBD and apheresis platelets were clinically equivalent, with approximately 16% indicating that they did not have an opinion on their equivalency and 14% indicating that they were not clinically equivalent. Forty-four percent of respondents felt that their customers would agree or strongly agree that these products are clinically equivalent, while 26% felt that their customers did not know or were neutral on clinical equivalency. The main barrier to WBD platelet implementation was logistic/inventory management issues, followed by bacterial contamination risk mitigation. There were 21/43 (49%) respondents who indicated they are not considering producing WBD platelets to mitigate shortages. Respondents indicated they might begin producing WBD platelets if there was evidence of increasing customer demand, increased reimbursement, inability to supply apheresis platelets, if pathogen reduction became available for WBD platelets, if the platelet shortage worsened. CONCLUSIONS: The majority of blood collectors consider WBD platelets clinically equivalent to apheresis, however wider adoption of WBD platelets is still hindered by challenges with logistics and inventory management.

Timing of RhD-positive red blood cell administration is associated with D-alloimmunization in injured patients.

BACKGROUND: The D-alloimmunization rate in trauma patients does not appear to depend on the number of RhD-positive units transfused. The effect of the timing and pattern of RhD-positive transfusions has not been evaluated. METHODS: RhD-negative trauma patients who were transfused with RhD-positive red blood cells (RBC) or low titer group O whole blood (collectively called RBCs) on at least two separate calendar days and who had antibody detection tests performed at least 14 days after the second RhD-positive RBC transfusion without receiving RhIg were included in the analysis. Patients whose anti-D was detected within 14 days of the index RhD-positive RBC transfusion were excluded. Patient demographics and the dates of RhD-positive RBC transfusions and results of antibody detection tests performed after the index transfusion were collected on eligible patients. RESULTS: There were 44/61 (72.1%) patients in whom anti-D was not detected (non-alloimmunized) and 17/61 (27.9%) in whom anti-D was detected (alloimmunized). The patients had similar demographics with trends towards higher median admission heart rates and lower median admission Glasgow Coma Scale values in the alloimmunized group. Both groups received statistically identical median quantities of RhD-positive RBCs (non-alloimmunized 5 vs. alloimmunized 4 units, p = .53), however, the alloimmunized group received all their RhD-positive RBCs over a significantly shorter period of time compared to the non-alloimmunized (median 4 vs. 15 days, respectively, p = .01). CONCLUSION: Receipt of all RhD-positive RBCs over a shorter period of time was associated with higher D-alloimmunization rates. These results need to be confirmed in larger studies.

Receipt of low titer group O whole blood does not lead to hemolysis in children weighing less than 20 kilograms.

OBJECTIVE: The safety of Low Titer Group O Whole Blood (LTOWB) transfusion has not been well-studied in small children. METHODS: This is a single-center retrospective cohort study of pediatric recipients of RhD-LTOWB (June 2016-October 2022) who weigh less than 20 kilograms. Biochemical markers of hemolysis (lactate dehydrogenase, total bilirubin, haptoglobin, and reticulocyte count) and renal function (creatinine and potassium) were recorded on the day of LTOWB transfusion and post-transfusion days 1 and 2. Group O and non-Group O recipients were compared. RESULTS: Twenty-one children were included. Their median (interquartile range [IQR]) weight was 12 kg (12-18) with minimum 2.8 kg, and median (IQR) age was 3 years (1.75-5.00) with minimum 0.08 years (29 days old). The most common indication for transfusion was trauma (17/21; 81%). The median (IQR) volume of LTOWB transfused was 30 mL/kg (20-42). There were 9 non-group O and 12 group O recipients. There were no statistically significant differences in the median concentrations of any of the biochemical markers of hemolysis or the renal function markers between the non-group O and the group O recipients at any of the three time points (p > 0.05 for all comparisons). There were also no statistically significant differences in demographic parameters or clinical outcomes including 28-day mortality, length of stay, ventilator days, and venous thromboembolism between the groups. No transfusion reactions were reported in either group. CONCLUSION: These data suggest LTOWB use is safe in children weighing less than 20 kg. Further multi-center studies and larger cohorts are needed to confirm these results.

A rapid ABO and RhD test demonstrates high fidelity to blood bank testing for RhD typing.

BACKGROUND: The rapid provision of blood products is life-saving for patients with massive hemorrhage. Ideally, RhD-negative blood products would be supplied to a woman of childbearing potential whose Rh type is unknown due to the risk of D-alloimmunization and the potential for hemolytic disease of the fetus and newborn to occur if RhD-positive blood products are transfused. Therefore, there is a need for a test that rapidly determines her RhD type. This study compared the RhD type determined using a rapid ABO and RhD test to the RhD type determined by an immunohematology reference laboratory. METHODS: After receiving ethics review board approval, 200 random, unique, deidentified patient samples that had undergone routine pretransfusion testing in an immunohematology reference laboratory using column agglutination technology were collected and tested using a rapid ABO and RhD test (Eldoncard Home kit 2511). The RhD typing results from these two methods were compared to determine the accuracy of the rapid ABO and RhD test. RESULTS: The rapid ABO and RhD test produced results that were concordant with the transfusion service's results in 199/200 (99.5%) of cases, with a negative predictive value of 98.2% and 99.3% sensitivity. The single outlier was likely an RhD variant due to its serological characteristics. DISCUSSION: These data indicate that this rapid ABO and RhD test could be used for the rapid determination of a patient's RhD type, perhaps even in the emergency department, which could guide the selection of blood products provided during their resuscitation.

Parent perceptions of emergent blood transfusion in children.

BACKGROUND: RhD-negative blood products are in chronic short supply leading to renewed interest in utilizing RhD-positive blood products for emergency transfusions. This study assessed parental perceptions of emergency RhD-positive blood use in children. METHODS: A survey of parents/guardians was conducted on their tolerance of transfusing RhD-positive blood to RhD-negative female children ≤17 years old at four level 1 pediatric hospitals. RESULTS: In total, 621 parents/guardians were approached of whom 378/621 (61%) completed the survey in its entirety and were included in the analysis. Respondents were mostly females [295/378 (78%)], White [242/378 (64%)], had some college education [217/378 (57%)] and less than $60,000 annual income [193/378 (51%)]. Respondents had a total of 547 female children. Most children's ABO [320/547 (59%)] and RhD type [348/547 (64%)] were not known by their parents; of children with known RhD type, 58/186 (31%) were RhD-negative. When the risk of harm to a future fetus was given as 0-6%, more than 80% of respondents indicated that they were likely to accept RhD-positive blood transfusions on behalf of RhD-negative female children in a life-threatening situation. The rate of willingness to accept emergent RhD-incompatible blood transfusions significantly increased as the potential survival benefit of the transfusion increased. CONCLUSION: Most parents were willing to accept RhD-positive blood products on behalf of RhD-negative female children in an emergency situation. Further discussions and evidence-based guidelines on transfusing RhD-positive blood products to RhD-unknown females in emergency settings are needed.

Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients.

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.

Serologic reactivity of unidentified specificity in antenatal testing and hemolytic disease of the fetus and newborn: The BEST collaborative study.

BACKGROUND: The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN). STUDY DESIGN AND METHODS: Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined. RESULTS: SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibody reactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibody reactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188). CONCLUSION: The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.

Hemostatic In Vitro Properties of Novel Plasma Supernatants Produced from Late-storage Low-titer Type O Whole Blood.

BACKGROUND: The use of low-titer group O whole blood is increasing. To reduce wastage, unused units can be converted to packed red blood cells. Supernatant is currently discarded post-conversion; however, it could be a valuable transfusable product. The aim of this study was to evaluate supernatant prepared from late-storage low-titer group O whole blood being converted to red blood cells, hypothesizing it will have higher hemostatic activity compared to fresh never-frozen liquid plasma. METHODS: Low-titer group O whole blood supernatant (n = 12) prepared on storage day 15 was tested on days 15, 21, and 26 and liquid plasma (n = 12) on 3, 15, 21, and 26. Same-day assays included cell counts, rotational thromboelastometry, and thrombin generation. Centrifuged plasma from units was banked for microparticle characterization, conventional coagulation, clot structure, hemoglobin, and additional thrombin generation assays. RESULTS: Low-titer group O whole blood supernatant contained more residual platelets and microparticles compared to liquid plasma. At day 15, low-titer group O whole blood supernatant elicited a faster intrinsic clotting time compared to liquid plasma (257 ± 41 vs. 299 ± 36 s, P = 0.044), and increased clot firmness (49 ± 9 vs. 28 ± 5 mm, P < 0.0001). Low-titer group O whole blood supernatant showed more significant thrombin generation compared to liquid plasma (day 15 endogenous thrombin potential 1,071 ± 315 vs. 285 ± 221 nM·min, P < 0.0001). Flow cytometry demonstrated low-titer group O whole blood supernatant contained significantly more phosphatidylserine and CD41+ microparticles. However, thrombin generation in isolated plasma suggested residual platelets in low-titer group O whole blood supernatant were a greater contributor than microparticles. Additionally, low-titer group O whole blood supernatant and liquid plasma showed no difference in clot structure, despite higher CD61+ microparticle presence. CONCLUSIONS: Plasma supernatant produced from late-storage low-titer group O whole blood shows comparable, if not enhanced, in vitro hemostatic efficacy to liquid plasma.

Low-titer group O whole blood in military ground ambulances: Lessons from the Israel Defense Forces initial experience.

BACKGROUND: Cold-stored low-titer group O whole blood (LTOWB) has become increasingly utilised in both prehospital and in-hospital settings for resuscitation of traumatic haemorrhage. However, implementing the use of LTOWB to ground medical teams has been limited due to logistic challenges. METHODS: In 2022, the Israel Defense Forces (IDF) started using LTOWB in ambulances for the first time in Israel. This report details the initial experience of this rollout and presents a case-series of the first patients treated with LTOWB. RESULTS: Between January-December 2022, seven trauma patients received LTOWB administered by ground IDF intensive care ambulances after presenting with profound shock. Median time from injury to administration of LTOWB was 35 min. All patients had evidence of severe bleeding upon hospital arrival with six undergoing damage control laparotomy and all but one surviving to discharge. CONCLUSIONS: The implementation of LTOWB in ground medical units is in its early stages, but continued experience may demonstrate its feasibility, safety, and effectiveness in the prehospital setting. Further research is necessary to fully understand the indications, methodology, and benefits of LTOWB in resuscitating severely injured trauma patients in this setting.

Prehospital Tranexamic Acid Administration in Pediatric Trauma Patients: A Propensity-Matched Analysis of the Israeli Defense Forces Registry.

OBJECTIVES: Tranexamic acid (TXA) administration confers a survival benefit in bleeding trauma patients; however, data regarding its use in pediatric patients are limited. This study evaluates the prehospital treatment with TXA in pediatric trauma patients treated by the Israel Defense Forces Medical Corps (IDF-MC). DESIGN: Retrospective, cohort study using the Israel Defense Forces registry, 2011-2021. PATIENTS: Pediatric trauma patients less than 18 years old. We excluded patients pronounced dead at the scene. INTERVENTIONS: None. SETTING: All cases of pediatric trauma in the registry were assessed for treatment with TXA. Propensity score matching was used to assess the association between prehospital TXA administration and mortality. MEASUREMENTS AND MAIN RESULTS: Overall, 911 pediatric trauma patients were treated with TXA by the IDF-MC teams; the median (interquartile) age was 10 years (5-15 yr), and 72.8% were male. Seventy patients (7.6%) received TXA, with 52 of 70 (74%) receiving a 1,000 mg dose (range 200-1,000 mg). There were no prehospital adverse events associated with the use of TXA (upper limit of 95% CI for 0/70 is 4.3%). Compared with pediatric patients who did not receive TXA, patients receiving TXA were more likely to suffer from shock (40% vs 10.7%; p < 0.001), sustain more penetrating injuries (72.9% vs 31.7%; p < 0.001), be treated with plasma or crystalloids (62.9% vs 11.4%; p < 0.001), and undergo more lifesaving interventions (24.3% vs 6.2%; p < 0.001). The propensity score matching failed to identify an association between TXA and lesser odds of mortality, although a lack of effect (or even adverse effect) could not be excluded (non-TXA: 7.1% vs TXA: 4.3%, odds ratio = 0.584; 95% CI 0.084-3.143; p = 0.718). CONCLUSIONS: Although prehospital TXA administration in the pediatric population is feasible with adverse event rate under 5%, more research is needed to determine the appropriate approach to pediatric hemostatic resuscitation and the role of TXA in this population.

Protocol: identifying policy, system, and environment change interventions to enhance availability of blood for transfusion in Kenya, a mixed-methods study.

BACKGROUND: Safe blood is essential for the care of patients with life-threatening anemia and hemorrhage. Low blood donation rates, inefficient testing procedures, and other supply chain disruptions in blood administration affect patients in low-resource settings across Sub-Saharan countries, including Kenya. Most efforts to improve access to transfusion have been unidimensional, usually focusing on only point along the blood system continuum, and have excluded community stakeholders from early stages of intervention development. Context-appropriate interventions to improve the availability of safe blood at the point of use in low-resource settings are of paramount importance. Thus, this protocol proposes a multifaceted approach to characterize the Kenyan blood supply chain through quantitative and qualitative analyses as well as an industrial engineering approach. METHODS: This study will use a mixed-methods approach in addition to engineering process mapping, modeling and simulation of blood availability in Kenya. It will be guided by a multidimensional three-by-three-by-three matrix: three socioeconomic settings, three components of the blood system continuum, and three levels of urgency of blood transfusion. Qualitative data collection includes one-on-one interviews and focus group discussions with stakeholders across the continuum to characterize ground-level deficits and potential policy, systems, and environment (PSE) interventions. Prospectively-collected quantitative data will be used to estimate blood collection and transfusion of blood. We will create a process map of the blood system continuum to model the response to PSE changes proposed by stakeholders. Lastly, we will identify those PSE changes that may have the greatest impact on blood transfusion availability, accounting for differences across socioeconomic settings and levels of urgency. DISCUSSION: Identifying and prioritizing community-driven interventions to improve blood supply in low-resource settings are of utmost importance. Varied constraints in blood collection, processing, delivery, and use make each socioeconomic setting unique. Using a multifaceted approach to understand the Kenyan blood supply and model the response to stakeholder-proposed PSE changes may lead to identification of contextually appropriate intervention targets to meet the transfusion needs of the population.