Use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for trauma and its performance in Japan over the past 18 years: a nationwide descriptive study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to control massive hemorrhages. Although there is no consensus on the efficacy of REBOA, it remains an option as a bridging therapy in non-trauma centers where trauma surgeons are not available. To better understand the current landscape of REBOA application, we examined changes in its usage, target population, and treatment outcomes in Japan, where immediate hemostasis procedures sometimes cannot be performed. METHODS: This retrospective observational study used the Japan Trauma Data Bank data. All cases in which REBOA was performed between January 2004 and December 2021 were included. The primary outcome was the in-hospital mortality rate. We analyzed mortality trends over time according to the number of cases, number of centers, severity of injury, and overall and subgroup mortality associated with REBOA usage. We performed a logistic analysis of mortality trends over time, adjusting for probability of survival based on the trauma and injury severity score. RESULTS: Overall, 2557 patients were treated with REBOA and were deemed eligible for inclusion. The median age of the participants was 55 years, and male patients constituted 65.3% of the study population. Blunt trauma accounted for approximately 93.0% of the cases. The number of cases and facilities that used REBOA increased until 2019. While the injury severity score and revised trauma score did not change throughout the observation period, the hospital mortality rate decreased from 91.3 to 50.9%. The REBOA group without severe head or spine injuries showed greater improvement in mortality than the all-patient group using REBOA and all-trauma patient group. The greatest improvement in mortality was observed in patients with systolic blood pressure ≥ 80 mmHg. The adjusted odds ratios for hospital mortality steadily declined, even after adjusting for the probability of survival. CONCLUSIONS: While there was no significant change in patient severity, mortality of patients treated with REBOA decreased over time. Further research is required to determine the reasons for these improvements in trauma care.

Hyperbaric oxygen therapy improves the efficacy of conventional supportive treatment for late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: This study aims to investigate the efficacy and safety of hyperbaric oxygen therapy (HBOT) in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. METHODS: This retrospective analysis included 16 patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation between 2016 and 2022. Among them, 8 patients received HBOT in addition to conventional treatment, while the other 8 received only conventional treatment. The clinical efficacy and safety of HBOT were evaluated by comparing the Numeric Rating Scale pain scores and clinical grades of hematuria before and after treatment, reflecting the patients' urinary pain and hematuria status. RESULTS: The patients were divided into two groups based on whether they received HBOT. The group that received HBOT (n = 8) had a shorter duration of illness compared to the non-HBOT group (n = 8) (p < 0.05). The time for the NRS to decrease to below 2 was also shorter in the HBOT group. Furthermore, the patients who received HBOT did not experience any significant adverse reactions. CONCLUSION: The combination of conventional treatment and hyperbaric oxygen therapy (HBOT) has been shown to improve symptoms such as urinary pain, frequency, urgency, and hematuria in patients with late-onset hemorrhagic cystitis after transplantation. This approach has been proven to be safe and effective.

AAV mediated genome engineering with a bypass coagulation factor alleviates the bleeding phenotype in a murine model of hemophilia B.

It is crucial to develop a long-term therapy that targets hemophilia A and B, including inhibitor-positive patients. We have developed an Adeno-associated virus (AAV) based strategy to integrate the bypass coagulation factor, activated FVII (murine, mFVIIa) gene into the Rosa26 locus using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 mediated gene-editing. AAV vectors designed for expression of guide RNA (AAV8-gRNA), Cas9 (AAV2 neddylation mutant-Cas9), and mFVIIa (AAV8-mFVIIa) flanked by homology arms of the target locus were validated in vitro. Hemophilia B mice were administered with AAV carrying gRNA, Cas9 (1 × 1011 vgs/mouse), and mFVIIa with homology arms (2 × 1011 vgs/mouse) with appropriate controls. Functional rescue was documented with suitable coagulation assays at various time points. The data from the T7 endonuclease assay revealed a cleavage efficiency of 20-42 %. Further, DNA sequencing confirmed the targeted integration of mFVIIa into the safe-harbor Rosa26 locus. The prothrombin time (PT) assay revealed a significant reduction in PT in mice that received the gene-editing vectors (22 %), and a 13 % decline in mice that received only the AAV-FVIIa when compared to mock treated mice, 8 weeks after vector administration. Furthermore, FVIIa activity in mice that received triple gene-editing vectors was higher (122.5mIU/mL vs 28.8mIU/mL) than the mock group up to 15 weeks post vector administration. A hemostatic challenge by tail clip assay revealed that hemophilia B mice injected with only FVIIa or the gene-editing vectors had significant reduction in blood loss. In conclusion, AAV based gene-editing facilitates sustained expression of coagulation FVIIa and phenotypic rescue in hemophilia B mice.

Stop the Bleed® in medical schools: Early advocacy and promising results.

OBJECTIVE: We hypothesized that medical students would be empowered by hemorrhage-control training and would support efforts to include Stop the Bleed® (STB) in medical education. DESIGN: This is a multi-institution survey study. Surveys were administered immediately following and 6 months after the course. SETTING: This study took place at the Association of American Medical Colleges-accredited medical schools in the United States. PARTICIPANTS: Participants were first-year medical students at participating institutions. A total of 442 students completed post-course surveys, and 213 students (48.2 percent) also completed 6-month follow-up surveys. INTERVENTION: An 1-hour, in-person STB course. MAIN OUTCOMES MEASURES: Student empowerment was measured by Likert-scale scoring, 1 (Strongly Disagree) to 5 (Strongly Agree). The usage of hemorrhage-control skills was also measured. RESULTS: A total of 419 students (95.9 percent) affirmed that the course taught the basics of bleeding control, and 169 (79.3 percent) responded positively at follow-up, with a significant decrease in Likert response (4.65, 3.87, p < 0.001). Four hundred and twenty-three students (97.0 percent) affirmed that they would apply bleeding control skills to a patient, and 192 (90.1 percent) responded positively at follow-up (4.61, 4.19, p < 0.001). Three hundred and sixty-one students (82.8 percent) believed that they were able to save a life, and 109 (51.2 percent) responded positively at follow-up (4.14, 3.56, p < 0.001). Four hundred and twenty-five students (97.0 percent) would recommend the course to another medical student, and 196 (92.0 percent) responded positively at follow-up (4.68, 4.31, p < 0.001). Six students (2.8 percent) used skills on live patients, with success in five of the six instances. CONCLUSIONS: Medical students were empowered by STB and have used hemorrhage-control skills on live victims. Medical students support efforts to include STB in medical education.

COMBAT-C: COntrol of Major Bleeding by Application of Tourniquets over Clothing.

INTRODUCTION: External bleeding is the leading cause of preventable trauma-related death. In certain circumstances, tourniquet application over clothing may be necessary. Therefore, the aim of this study was to assess the effectiveness of tourniquets over different clothing setups. METHODS: Three windlass tourniquets (CAT, SAMXT, SOFTT-W) were applied over nine different clothing setups and without clothing on the Hapmed™ Tourniquet Trainer. We compared each tourniquet in each clothing setup to the tourniquet trainer that was not dressed, and we compared the three tourniquets within each clothing setup concerning blood loss, applied pressure and application time. Regression analysis of the effect of thickness, mean weight, mean deformation, application time, and applied pressure on blood loss was performed. RESULTS: Although blood loss was significantly greater in the CAT and SAMXT tourniquets when they were applied over leather motorcycle trousers, the overall findings showed that the clothing setups significantly reduced or did not affect blood loss. The mean blood loss was the lowest with CAT and the highest with SOFTT-W. The measured mean pressures were lower than 180 mmHg in four out of nine clothing setups with SOFTT-W, but CAT and SAMXT always exceeded this threshold. CAT had the fastest application time. Blood loss was significantly influenced by applied pressure and application time but was influenced to a far lesser degree by clothing parameters. CONCLUSION: The effects of the clothing setups were of little clinical relevance, except for leather motorcycle trousers. The effects of rugged protective equipment, e.g., hazard suits, are conceivable and need to be tested for specific garments with the tourniquet intended for use. No clothing parameter for predicting tourniquet effectiveness could be identified.

A lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: A prospective single-center analysis.

BACKGROUND: Plasma exchange (PLEX) therapy is indicated for several disorders. The 5% albumin is often used as a sole replacement fluid during most PLEX. However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%. Although most coagulation factors recover to hemostatic levels within 24 h post-PLEX, fibrinogen requires 48-72 h to recover. Fibrinogen is the key coagulation protein for hemostasis. Therefore, fibrinogen is often monitored during the acute course of PLEX, and plasma is supplemented to prevent bleeding if fibrinogen is <100 mg/dL. STUDY DESIGN AND METHODS: We conducted a prospective, single-center, observational study to evaluate bleeding risk in adults who received an acute course of PLEX with a fibrinogen level of 80-100 mg/dL without plasma supplementation during the procedure or before central venous catheter removal. The study group was compared to patients with plasma fibrinogen >100 mg/dL. RESULTS: Among the 275 patients who received 1406 PLEXes, 62 patients (23%) who underwent 323 PLEXes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants. In contrast, out of 275 patients, 143 (52%) with fibrinogen levels >100 mg/dL received 751 PLEX treatments, and bleeding occurred in 2 (1%) while on low-molecular-weight heparin. CONCLUSIONS: Our findings suggest that a pre-procedure fibrinogen threshold of 80-100 mg/dL without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation.

Arterial embolization in the treatment of multiple renal and hepatic hamartomas with spontaneous hemorrhage and 2-year follow-up: a case report.

BACKGROUND: Hamartoma is a common benign tumor that usually occurs in the kidney, liver, lung, and pancreas. Large renal hamartomas may spontaneously rupture and hemorrhage, which is potentially life-threatening. CASE PRESENTATION: This report describes a 46-year-old Han Chinese female patient with multiple renal and hepatic hamartomas with rupture and hemorrhage of giant hamartoma in the left kidney. She underwent arterial embolization three times successively, and her condition was stable during the 2-year follow-up. This report includes a review of the relevant literature CONCLUSIONS: the findings in this report and previous literature suggest that arterial embolization can not only rapidly treat hamartoma hemorrhage in the acute phase but can also effectively control multiple lesions in the long term after repeated multisite arterial embolization.

A randomized controlled trial comparison of PTEBL and traditional teaching methods in "Stop the Bleed" training.

BACKGROUND: The Stop the Bleed (STB) training program was launched by the White House to minimize hemorrhagic deaths. Few studies focused on the STB were reported outside the United States. This study aimed to evaluate the effectiveness of a problem-, team- and evidence-based learning (PTEBL) approach to teaching, compared to traditional teaching methods currently employed in STB courses in China. METHODS: This study was a parallel group, unmasked, randomised controlled trial. We included third-year medical students of a five-year training program from the Xiangya School of Medicine, Central South University who voluntarily participated in the trial. One hundred fifty-three medical students were randomized (1:1) into the PTEBL group (n = 77) or traditional group (n = 76). Every group was led by a single instructor. The instructor in the PTEBL group has experienced in educational reform. However, the instructor in the traditional group follows a traditional teaching mode. The teaching courses for both student groups had the same duration of four hours. Questionnaires were conducted to assess teaching quality before and after the course. The trial was registered in the Central South University (No. 2021JY188). RESULTS: In the PTEBL group, students reported mastery in three fundamental STB skills-Direct Finger Compression (61/77, 79.2%), Packing (72/77, 93.8%), and Tourniquet Placement (71/77, 92.2%) respectively, while 76.3% (58/76), 89.5% (68/76), and 88.2% (67/76) of students in the traditional group (P > 0.05 for each pairwise comparison). 96.1% (74/77) of students in the PTEBL group felt prepared to help in an emergency, while 90.8% (69/76) of students in the traditional group (P > 0.05). 94.8% (73/77) of students reported improved teamwork skills after the PTEBL course, in contrast with 81.6% (62/76) of students in the traditional course (P = 0.011). Furthermore, a positive correlation was observed between improved clinical thinking skills and improved teamwork skills (R = 0.82, 95% CI: 0.74-0.88; P < 0.001). CONCLUSIONS: Compared with the traditional teaching method, the PTEBL method was superior in teaching teamwork skills, and has equally effectively taught hemostasis techniques in the emergency setting. The PTEBL method can be introduced to the STB training in China.

Nomogram for predicting in-hospital mortality in trauma patients undergoing resuscitative endovascular balloon occlusion of the aorta: a retrospective multicenter study.

Recently, resuscitative endovascular balloon occlusion of the aorta (REBOA) had been introduced as an innovative procedure for severe hemorrhage in the abdomen or pelvis. We aimed to investigate risk factors associated with mortality after REBOA and construct a model for predicting mortality. This multicenter retrospective study collected data from 251 patients admitted at five regional trauma centers across South Korea from 2015 to 2022. The indications for REBOA included patients experiencing hypovolemic shock due to hemorrhage in the abdomen, pelvis, or lower extremities, and those who were non-responders (systolic blood pressure (SBP) < 90 mmHg) to initial fluid treatment. The primary and secondary outcomes were mortality due to exsanguination and overall mortality, respectively. After feature selection using the least absolute shrinkage and selection operator (LASSO) logistic regression model to minimize overfitting, a multivariate logistic regression (MLR) model and nomogram were constructed. In the MLR model using risk factors selected in the LASSO, five risk factors, including initial heart rate (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.98-1.00; p = 0.030), initial Glasgow coma scale (aOR, 0.86; 95% CI 0.80-0.93; p < 0.001), RBC transfusion within 4 h (unit, aOR, 1.12; 95% CI 1.07-1.17; p < 0.001), balloon occlusion type (reference: partial occlusion; total occlusion, aOR, 2.53; 95% CI 1.27-5.02; p = 0.008; partial + total occlusion, aOR, 2.04; 95% CI 0.71-5.86; p = 0.187), and post-REBOA systolic blood pressure (SBP) (aOR, 0.98; 95% CI 0.97-0.99; p < 0.001) were significantly associated with mortality due to exsanguination. The prediction model showed an area under curve, sensitivity, and specificity of 0.855, 73.2%, and 83.6%, respectively. Decision curve analysis showed that the predictive model had increased net benefits across a wide range of threshold probabilities. This study developed a novel intuitive nomogram for predicting mortality in patients undergoing REBOA. Our proposed model exhibited excellent performance and revealed that total occlusion was associated with poor outcomes, with post-REBOA SBP potentially being an effective surrogate measure.

Opportunity for a Community Health Fair Model of Bleeding Control Training.

BACKGROUND: Traumatic hemorrhage is a prevalent cause of death nationally, with >50% of civilian deaths estimated to be preventable with more timely intervention. This study investigated the efficacy of training large and diverse audiences in bleeding control methods including tourniquets in community health fair settings. METHODS: A booth was utilized for bleeding control training at community health fairs via direct demonstrations of pressure, wound packing, and commercial and improvised tourniquet application followed by hands-on practice. Participants self-rated their perceived abilities while instructors rated the participant competency. RESULTS: 117 community members participated during two fairs, though not every person completed every portion of the training. Average age was 33 (range 6-82) and the majority were female (65.0%). There was no difference in self-perceived skill compared to trainer grading of participant's ability to identify life-threatening bleeding (112 (97.4%) vs 106 (97.2%); P = 1), apply pressure (113 (98.3%) vs 106 (97.2%); P = .68), and pack a wound (102 (88.7%) vs 92 (84.4%); P = .43). No difference in difficulty was noted in placing commercial vs improvised tourniquets (16 (43%) vs 14 (45%); P = .87). However, participants were overconfident in their ability to place tourniquets compared to trainer grading, respectively (112 (98.2%) vs 100 (91.7%; P = .03)). DISCUSSION: Community fair classes provide opportunities to train large and diverse audiences in bleeding control techniques. However, participants overestimated their ability to appropriately apply tourniquets. Further investigation is needed into best educational approaches to optimize the impact of bleeding control kits that have been distributed in multiple states.

A review and analysis of outcomes in randomized clinical trials of plasma transfusion in patients with bleeding or for the prevention of bleeding: The BEST collaborative study.

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.

Defining success in haemophilia care - Are we doing it right?

INTRODUCTION: Transformational advances have occurred in the management of haemophilia in the last decade leading to much better outcomes. However, a detailed and critical examination of its assessment and reporting show gaps in many aspects. These are discussed in this review. METHODS: The relevant literature related to different aspects of management of haemophilia was reviewed to identify gaps which need to be addressed. These include detection and diagnosis of haemophilia, documentation and reporting of joint bleeding, its management and methods of reporting in clinical trials and practice, aspects of personalizing care as well as access to therapeutic products and the need for and organization of comprehensive care. RESULTS: Current diagnostic approaches have more than doubled the identified number of persons with haemophilia (PWH) over the last 25 years but still constitute only ∼30% of the expected number. Joint bleeding is the primary indicator of disease severity and treatment efficacy, but there is lack of consistency and standardization in the way it is recorded and reported. Its continued use as an efficacy measure of modern treatments which maintain steady state factor levels or equivalence of >5% will lack sensitivity. The treatment of acute haemarthrosis has focussed on haemostasis and pain control, ignoring the role of inflammation in joint damage. Phenotypic heterogeneity of severe haemophilia has recognized clinical and laboratory variations based on haemostasis but not differences in local response to blood in the joint. At the organizational level, IU/capita provides a relevant measure of access to therapeutic products when the detection rate is ∼100% but is fallaciously low when detection rates are very low. With highly effective modern therapies for haemophilia and nearly no bleeding, the concept of comprehensive care team will need modifications. CONCLUSION: As haemophilia care advances, a deeper dive is needed into the details of various aspects its management to ensure consistency and contemporary relevance.

Idiopathic Spontaneous Rupture of a Subcostal Artery in a Patient Undergoing Hemodialysis: A Case Report.

The spontaneous rupture of a subcostal (12th intercostal) artery is exceptionally rare and could be fatal, requiring early diagnosis and treatment. Only one case of intercostal artery (ICA) bleeding in a patient undergoing hemodialysis (HD) has been reported. We additionally describe a 41-year-old man undergoing HD who presented with a spontaneous hemoperitoneum and shock resulting from a subcostal artery rupture. He initially complained of diffuse abdominal pain and dizziness at the emergency room. His abdomen was bloated, and there was tenderness in the right upper quadrant area. Enhanced computed tomography and arteriography revealed a rupture of the right subcostal artery. After the super-selection of the bleeding artery by a microcatheter, embolization was performed using a detachable coil and gelfoam. In a subsequent arteriogram, additional contrast leakage was no longer detected, and his blood pressure was restored to normal. The patient was discharged without any sequelae. He was followed up at our HD center without recurrence of ICA bleeding. To the best of our knowledge, this is the second case in the English literature documenting a spontaneous ICA rupture in a patient undergoing HD. This case indicates that injury to ICA should be suspected when patients undergoing HD complain of abdominal or chest pain and dizziness, although it is very rare.

Characteristics of traumatic major haemorrhage in a tertiary trauma center.

BACKGROUND: Major traumatic haemorrhage is potentially preventable with rapid haemorrhage control and improved resuscitation techniques. Although advances in prehospital trauma management, haemorrhage is still associated with high mortality. The aim of this study was to use a recent pragmatic transfusion-based definition of major bleeding to characterize patients at risk of major bleeding and associated outcomes in this cohort after trauma. METHODS: This was a retrospective cohort study including all trauma patients (n = 7020) admitted to a tertiary trauma center from January 2015 to June 2020. The major bleeding cohort (n = 145) was defined as transfusion of 4 units of any blood components (red blood cells, plasma, or platelets) within 2 h of injury. Univariate and multivariable logistic regression analyses were performed to identify risk factors for 24-hour and 30-day mortality post trauma admission. RESULTS: In the major bleeding cohort (n = 145; 145/7020, 2.1% of the trauma population), there were 77% men (n = 112) and 23% women (n = 33), median age 39 years [IQR 26-53] and median Injury Severity Score (ISS) was 22 [IQR 13-34]. Blunt trauma dominated over penetrating trauma (58% vs. 42%) where high-energy fall was the most common blunt mechanism and knife injury was the most common penetrating mechanism. The major bleeding cohort was younger (OR 0.99; 95% CI 0.98 to 0.998, P = 0.012), less female gender (OR 0.66; 95% CI 0.45 to 0.98, P = 0.04), and had more penetrating trauma (OR 4.54; 95% CI 3.24 to 6.36, P = 0.001) than the rest of the trauma cohort. A prehospital (OR 2.39; 95% CI 1.34 to 4.28; P = 0.003) and emergency department (ED) (OR 6.91; 95% CI 4.49 to 10.66, P = 0.001) systolic blood pressure < 90 mmHg was associated with the major bleeding cohort as well as ED blood gas base excess < -3 (OR 7.72; 95% CI 5.37 to 11.11; P < 0.001) and INR > 1.2 (OR 3.09; 95% CI 2.16 to 4.43; P = 0.001). Emergency damage control laparotomy was performed more frequently in the major bleeding cohort (21.4% [n = 31] vs. 1.5% [n = 106]; OR 3.90; 95% CI 2.50 to 6.08; P < 0.001). There was no difference in transportation time from alarm to hospital arrival between the major bleeding cohort and the rest of the trauma cohort (47 [IQR 38;59] vs. 49 [IQR 40;62] minutes; P = 0.17). However, the major bleeding cohort had a shorter time from ED to first emergency procedure (71.5 [IQR 10.0;129.0] vs. 109.00 [IQR 54.0; 259.0] minutes, P < 0.001). In the major bleeding cohort, patients with penetrating trauma, compared to blunt trauma, had a shorter alarm to hospital arrival time (44.0 [IQR 35.5;54.0] vs. 50.0 [IQR 41.5;61.0], P = 0.013). The 24-hour mortality in the major bleeding cohort was 6.9% (10/145). All fatalities were due to blunt trauma; 40% (4/10) high energy fall, 20% (2/10) motor vehicle accident, 10% (1/10) motorcycle accident, 10% (1/10) traffic pedestrian, 10% (1/10) traffic other, and 10% (1/10) struck/hit by blunt object. In the logistic regression model, prehospital cardiac arrest (OR 83.4; 95% CI 3.37 to 2063; P = 0.007) and transportation time (OR 0.95, 95% CI 0.91 to 0.99, P = 0.02) were associated with 24-hour mortality. RESULTS: Early identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control. The major bleeding trauma cohort is a small part of the entire trauma population, and is characterized of being younger, male gender, higher ISS, and exposed to more penetrating trauma. Early identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control.

Patient sex and outcomes in children with life-threatening hemorrhage.

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.

Analyzing and modeling massive transfusion strategies and the role of fibrinogen-How much is the patient actually receiving?

BACKGROUND: Hemorrhage is a leading cause of preventable death in trauma, cardiac surgery, liver transplant, and childbirth. While emphasis on protocolization and ratio of blood product transfusion improves ability to treat hemorrhage rapidly, tools to facilitate understanding of the overall content of a specific transfusion strategy are lacking. Medical modeling can provide insights into where deficits in treatment could arise and key areas for clinical study. By using a transfusion model to gain insight into the aggregate content of massive transfusion protocols (MTPs), clinicians can optimize protocols and create opportunities for future studies of precision transfusion medicine in hemorrhage treatment. METHODS: The transfusion model describes the individual round and aggregate content provided by four rounds of MTP, illustrating that the total content of blood elements and coagulation factor changes over time, independent of the patient's condition. The configurable model calculates the aggregate hematocrit, platelet concentration, percent volume plasma, total grams and concentration of citrate, percent volume anticoagulant and additive solution, and concentration of clotting factors: fibrinogen, factor XIII, factor VIII, and von Willebrand factor, provided by the MTP strategy. RESULTS: Transfusion strategies based on a 1:1:1 or whole blood foundation provide between 13.7 and 17.2 L of blood products over four rounds. Content of strategies varies widely across all measurements based on base strategy and addition of concentrated sources of fibrinogen and other key clotting factors. DISCUSSION: Differences observed between modeled transfusion strategies provide key insights into potential opportunities to provide patients with precision transfusion strategy.

The first two years of the use of low titer group O whole blood during French Military overseas operations: A retrospective study.

BACKGROUND: On the battlefield, hemorrhage is the main cause of potentially preventable death. To reduce mortality due to hemorrhagic injuries, the French Military Medical Service (FMMS) has deployed low titer group O whole blood (LTOWB) since June 2021 during operation BARKHANE in the Sahel-Saharan strip. Questions persist regarding the circumstances under which the FMMS employs LTOWB during overseas operations. STUDY DESIGN: We performed a retrospective analysis of all LTOWB transfused by the FMMS during overseas operations in the Sahel-Saharan strip between June 1, 2021, and June 1, 2023. Information was collected from battlefield forward transfusion sheets. RESULTS: Over the 2-year study period, 40 units of LTOWB were transfused into 25 patients. Of the 25 patients, 18 were combat casualties and seven were transfused for non-trauma surgery. Of the 40 units of LTOWB transfused, 22 were provided during Role 2 care, 11 during tactical medical evacuation (MEDEVAC), and seven in light and mobile surgical units. Among combat casualties, LTOWB was the first blood product transfused in 13 patients. In combat casualties, 6 h post-trauma, the median ratio of plasma: red blood cells (RBCs) was 1.5, and the median equivalent platelet concentrate (PC) transfused was 0.17. No immediate adverse events related to LTOWB transfusion were reported. CONCLUSION: LTOWB is transfused by the FMMS during overseas operations from the tactical MEDEVAC until Role 2 care. Deployment of LTOWB by the FMMS enables an early high-ratio plasma/RBC transfusion and an early platelet transfusion for combat casualties.

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.