Evaluating patient factors, operative management and postoperative outcomes in trauma laparotomy patients worldwide: a protocol for a global observational multicentre trauma study.

INTRODUCTION: Trauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed operation. Variation likely exists in how these patients are managed and their subsequent outcomes, yet very little global data on the topic currently exists. The objective of the GOAL-Trauma study is to evaluate both patient and injury factors for those undergoing trauma laparotomy, their clinical management and postoperative outcomes. METHODS: We describe a planned prospective multicentre observational cohort study of patients undergoing trauma laparotomy. We will include patients of all ages who present to hospital with a blunt or penetrating injury and undergo a trauma laparotomy within 5 days of presentation to the treating centre. The study will collect system, patient, process and outcome data, following patients up until 30 days postoperatively (or until discharge or death, whichever is first). Our sample size calculation suggests we will need to recruit 552 patients from approximately 150 recruiting centres. DISCUSSION: The GOAL-Trauma study will provide a global snapshot of the current management and outcomes for patients undergoing a trauma laparotomy. It will also provide insight into the variation seen in the time delays for receiving care, the disease and patient factors present, and patient outcomes. For current standards of trauma care to be improved worldwide, a greater understanding of the current state of trauma laparotomy care is paramount if appropriate interventions and targets are to be identified and implemented.

Transforming research to improve therapies for trauma in the twenty-first century.

Improvements have been made in optimizing initial care of trauma patients, both in prehospital systems as well as in the emergency department, and these have also favorably affected longer term outcomes. However, as specific treatments for bleeding are largely lacking, many patients continue to die from hemorrhage. Also, major knowledge gaps remain on the impact of tissue injury on the host immune and coagulation response, which hampers the development of interventions to treat or prevent organ failure, thrombosis, infections or other complications of trauma. Thereby, trauma remains a challenge for intensivists. This review describes the most pressing research questions in trauma, as well as new approaches to trauma research, with the aim to bring improved therapies to the bedside within the twenty-first century.

A comparative analysis of tranexamic acid dosing strategies in traumatic major hemorrhage.

INTRODUCTION: Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus, or bolus plus infusion. The aim of this study was to determine the effect of different TXA dosing strategies on clinical outcomes in bleeding trauma patients. METHODS: Secondary analysis of a perpetual cohort study from a UK Level I trauma center. Adult patients who activated the local major hemorrhage protocol and received TXA were included. The primary outcome was 28-day mortality. Secondary outcomes were 24-hour mortality, multiple organ dysfunction syndrome, venous thromboembolism, and rotational thromboelastometry fibrinolysis. RESULTS: Over an 11-year period, 525 patients were included. Three dosing groups were identified: 1 g bolus only (n = 317), 1 g bolus +1 g infusion over 8 hours (n = 80), and 2 g bolus (n = 128). Demographics and admission physiology were similar, but there were differences in injury severity (median Injury Severity Score, 25, 29, and 25); and admission systolic blood pressure (median Systolic Blood Pressure, 99, 108, 99 mm Hg) across the 1-g, 1 g + 1 g, and 2-g groups. 28-day mortality was 21% in each treatment group. The incidence of multiple organ dysfunction syndrome was significantly higher in the bolus plus infusion group (84%) vs. 1 g bolus (64%) and 2 g bolus (62%) group, p = 0.002, but on multivariable analysis was nonsignificant. Venous thromboembolism rates were similar in the 1-g bolus (4%), 2 g bolus (8%) and bolus plus infusion groups (7%). There was no difference in rotational thromboelastometry maximum lysis at 24 hours: 5% in both the 1-g and 2-g bolus groups vs. 4% in bolus plus infusion group. CONCLUSION: Clinical outcomes and 24-hour fibrinolysis state were equivalent across three different dosing strategies of TXA. Single bolus administration is likely preferable to a bolus plus infusion regimen. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Group B or not group B? An association between ABO, early mortality, and organ dysfunction in major trauma patients with shock.

BACKGROUND: ABO blood group alters coagulation profiles in the general population and may influence outcomes after trauma. The relationship between trauma-induced coagulopathy, severe injury with hemorrhagic shock, and survival with respect to ABO group is unknown. OBJECTIVES: In severe hemorrhagic trauma, we aimed to characterize the association of ABO group with admission coagulation profiles, mortality, and immune-mediated complications. METHODS: Clinical and laboratory variables were examined from severely injured adult patients enrolled in a perpetual observational cohort study at a UK Major Trauma Center. Univariate and multivariate analyses were performed to determine differences in clinical outcomes (mortality, organ dysfunction, and critical care support). In a shock subgroup, we performed an exploratory analysis of rotational thromboelastometry parameters and coagulation biomarkers. RESULTS: In 1119 trauma patients, we found no difference in mortality between ABO groups. In patients with shock, 24-hour mortality was significantly lower in group B vs non-B groups (7% vs 16%, adjusted odds ratio [aOR], 0.19; P = .030), but there were increased rates of invasive ventilation (aOR, 3.34; P = .033), renal replacement therapy (aOR, 2.55; P = .037), and a trend for infection (aOR, 1.85; P = .067). Comparing patients with shock, group B vs non-B patients had 40% higher fibrinogen, 65% higher factor (F) VIII, 36% higher FIX, 20% higher FXIII, and 19% higher von Willebrand factor. CONCLUSION: In this observational study limited by single time-point sampling and subgroup analysis of trauma hemorrhage with shock, group B patients have enhanced hemostatic capability associated with early survival but with increased risk of immune-mediated complications.

Prothrombin complex concentrate (PCC) for treatment of trauma-induced coagulopathy: systematic review and meta-analyses.

BACKGROUND: Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the correction of TIC, but the efficacy, timing, and evidence to support its use in injured patients with hemorrhage are unclear. METHODS: A systematic search of published studies was performed on MEDLINE and EMBASE databases using standardized search equations. Ongoing studies were identified using clinicaltrials.gov. Studies investigating the use of PCC to treat TIC (on its own or in combination with other treatments) in adult major trauma patients were included. Studies involving pediatric patients, studies of only traumatic brain injury (TBI), and studies involving only anticoagulated patients were excluded. Primary outcomes were in-hospital mortality and venous thromboembolism (VTE). Pooled effects of PCC use were reported using random-effects model meta-analyses. Risk of bias was assessed for each study, and we used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. RESULTS: After removing duplicates, 1745 reports were screened and nine observational studies and one randomized controlled trial (RCT) were included, with a total of 1150 patients receiving PCC. Most studies used 4-factor-PCC with a dose of 20-30U/Kg. Among observational studies, co-interventions included whole blood (n = 1), fibrinogen concentrate (n = 2), or fresh frozen plasma (n = 4). Outcomes were inconsistently reported across studies with wide variation in both measurements and time points. The eight observational studies included reported mortality with a pooled odds ratio of 0.97 [95% CI 0.56-1.69], and five reported deep venous thrombosis (DVT) with a pooled OR of 0.83 [95% CI 0.44-1.57]. When pooling the observational studies and the RCT, the OR for mortality and DVT was 0.94 [95% CI 0.60-1.45] and 1.00 [95% CI 0.64-1.55] respectively. CONCLUSIONS: Among published studies of TIC, PCCs did not significantly reduce mortality, nor did they increase the risk of VTE. However, the potential thrombotic risk remains a concern that should be addressed in future studies. Several RCTs are currently ongoing to further explore the efficacy and safety of PCC.

Revisiting the promise, practice and progress of resuscitative endovascular balloon occlusion of the aorta.

PURPOSE OF REVIEW: The use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) to temporarily control bleeding and improve central perfusion in critically injured trauma patients remains a controversial topic. In the last decade, select trauma services around the world have gained experience with REBOA. We discuss the recent observational data together with the initial results of the first randomized control trial and provide a view on the next steps for REBOA in trauma resuscitation. RECENT FINDINGS: While the observational data continue to be conflicting, the first randomized control trial signals that in the UK, in-hospital REBOA is associated with harm. Likely a result of delays to haemorrhage control, views are again split on whether to abandon complex interventions in bleeding trauma patients and to only prioritize transfer to the operating room or to push REBOA earlier into the post injury phase, recognizing that some patients will not survive without intervention. SUMMARY: Better understanding of cardiac shock physiology provides a new lens in which to evaluate REBOA through. Patient selection remains a huge challenge. Invasive blood pressure monitoring, combined with machine learning aided decision support may assist clinicians and their patients in the future. The use of REBOA should not delay definitive haemorrhage control in those patients without impending cardiac arrest.

Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial.

Importance: Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage. Objective: To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol. Design, Setting, and Participants: CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion. Intervention: Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury. Main Outcomes and Measures: The primary outcome was all-cause mortality at 28 days in the intention-to-treat population. Results: Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%). Conclusions and Relevance: Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.

Nationwide analysis of prehospital tranexamic acid for trauma demonstrates systematic bias in adherence to treatment guidelines: a retrospective cohort study.

BACKGROUND: Prehospital (PH) tranexamic acid (TXA) improves survival from trauma haemorrhage. Injury mechanism, physiology, and sex demographics vary with patient age. The authors hypothesised that these factors influence TXA guideline compliance and examined national trends in PH use to identify any systematic biases in bleeding management. MATERIALS AND METHODS: The UK Trauma Audit and Research Network data for TXA eligible patients admitted to major trauma centres were divided into two cohorts: 2013-2015 ( n =32 072) and 2017-2019 ( n =14 974). Patients were stratified by PH, emergency department or no TXA use. Logistic regression models explored interaction between PH variables and TXA administration. Results are presented as odds ratios with a 95% CI. RESULTS: PH TXA use increased from 8% to 27% over time ( P <0.001). Only 3% of eligible patients who fell less than 2 m received PH TXA versus 63% with penetrating injuries ( P <0.001). Older patients eligible for PH TXA were less likely to receive it compared to younger patients [≥65 years old: 590 (13%) vs. <65 years old: 3361 (33%), P <0.001]. There was a significant interaction between age and sex with fewer older women receiving PH TXA. In shocked patients, one third of females compared to a fifth of men did not receive TXA ( P <0.001). There was a decrease in PH TXA use as age increased ( P <0.001). CONCLUSIONS: Despite a threefold increase in use, treatment guidance for PH TXA is not universally applied. Older people, women, and patients with low energy injury mechanisms appear to be systematically under treated. Training and education for PH providers should address these potential treatment biases.

Sonorheometry versus rotational thromboelastometry in trauma: a comparison of diagnostic and prognostic performance.

BACKGROUND: Rotational thromboelastometry (ROTEM) is used to rapidly identify trauma-induced coagulopathy (TIC) and direct targeted interventions in hemorrhaging trauma patients. A novel technology, Quantra System (HemoSonics), utilizes sonic estimation of elasticity via resonance sonorheometry, avoids mechanical clot interference, and may increase diagnostic accuracy, but there are limited data on bleeding in major trauma patients. OBJECTIVES: To compare the performance of Quantra with that of ROTEM for rapid diagnosis of TIC and prediction of transfusion requirements and mortality. METHODS: Samples were collected from adult trauma patients enrolled in a perpetual cohort study upon admission to a single level 1 trauma center between 2020 and 2021. Samples were analyzed using Quantra, ROTEM, multiple electrode aggregometry, and conventional coagulation assays. RESULTS: Samples from 209 patients were analyzed. Correlations were strong between Quantra and ROTEM parameters (for all, p < .001): clot stiffness (CS) and tissue factor-activated ROTEM (EXTEM) clot amplitude at 5 minutes (A5) (r = 0.90); fibrinogen contribution to CS and tissue factor-activated ROTEM with cytochalasin D (FIBTEM) A5 (r = 0.85); and platelet contribution to CS and EXTEM-FIBTEM A5 (r = 0.73). Although CS showed higher discrimination than EXTEM A5 in detecting TIC (international normalized ratio, >1.2; area under the receiver operating characteristic curve, 0.83 vs 0.79; p = .038), the ability of fibrinogen contribution to CS to detect hypofibrinogenemia (a fibrinogen level of <2g/L) was good but lower than that of FIBTEM A5 (area under the receiver operating characteristic curve, 0.79 vs 0.84; p = .027). There was no difference between Quantra and ROTEM in detecting a platelet count of <150 × 109/L, predicting rapid transfusion or mortality at 6 hours. CONCLUSION: Quantra and ROTEM have similar diagnostic performances in evaluating TIC and predicting clinically relevant outcomes. Larger studies are required to determine the utility of Quantra for goal-directed treatment of TIC.

A new global fibrinolysis capacity assay for the sensitive detection of hyperfibrinolysis and hypofibrinogenemia in trauma patients.

BACKGROUND: Conventional clotting tests are not expeditious enough to allow timely targeted interventions in trauma, and current point-of-care analyzers, such as rotational thromboelastometry (ROTEM), have limited sensitivity for hyperfibrinolysis and hypofibrinogenemia. OBJECTIVES: To evaluate the performance of a recently developed global fibrinolysis capacity (GFC) assay in identifying fibrinolysis and hypofibrinogenemia in trauma patients. METHODS: Exploratory analysis of a prospective cohort of adult trauma patients admitted to a single UK major trauma center and of commercially available healthy donor samples was performed. Lysis time (LT) was measured in plasma according to the GFC manufacturer's protocol, and a novel fibrinogen-related parameter (percentage reduction in GFC optical density from baseline at 1 minute) was derived from the GFC curve. Hyperfibrinolysis was defined as a tissue factor-activated ROTEM maximum lysis of >15% or LT of ≤30 minutes. RESULTS: Compared to healthy donors (n = 19), non-tranexamic acid-treated trauma patients (n = 82) showed shortened LT, indicative of hyperfibrinolysis (29 minutes [16-35] vs 43 minutes [40-47]; p < .001). Of the 63 patients without overt ROTEM-hyperfibrinolysis, 31 (49%) had LT of ≤30 minutes, with 26% (8 of 31) of them requiring major transfusions. LT showed increased accuracy compared to maximum lysis in predicting 28-day mortality (area under the receiver operating characteristic curve, 0.96 [0.92-1.00] vs 0.65 [0.49-0.81]; p = .001). Percentage reduction in GFC optical density from baseline at 1 minute showed comparable specificity (76% vs 79%) to ROTEM clot amplitude at 5 minutes from tissue factor-activated ROTEM with cytochalasin D in detecting hypofibrinogenemia but correctly reclassified >50% of the patients with false negative results, leading to higher sensitivity (90% vs 77%). CONCLUSION: Severe trauma patients are characterized by a hyperfibrinolytic profile upon admission to the emergency department. The GFC assay is more sensitive than ROTEM in capturing hyperfibrinolysis and hypofibrinogenemia but requires further development and automation.

Association of red blood cells and plasma transfusion versus red blood cell transfusion only with survival for treatment of major traumatic hemorrhage in prehospital setting in England: a multicenter study.

BACKGROUND: In-hospital acute resuscitation in trauma has evolved toward early and balanced transfusion resuscitation with red blood cells (RBC) and plasma being transfused in equal ratios. Being able to deliver this ratio in prehospital environments is a challenge. A combined component, like leukocyte-depleted red cell and plasma (RCP), could facilitate early prehospital resuscitation with RBC and plasma, while at the same time improving logistics for the team. However, there is limited evidence on the clinical benefits of RCP. OBJECTIVE: To compare prehospital transfusion of combined RCP versus RBC alone or RBC and plasma separately (RBC + P) on mortality in trauma bleeding patients. METHODS: Data were collected prospectively on patients who received prehospital transfusion (RBC + thawed plasma/Lyoplas or RCP) for traumatic hemorrhage from six prehospital services in England (2018-2020). Retrospective data on patients who transfused RBC from 2015 to 2018 were included for comparison. The association between transfusion arms and 24-h and 30-day mortality, adjusting for age, injury mechanism, age, prehospital heart rate and blood pressure, was evaluated using generalized estimating equations. RESULTS: Out of 970 recruited patients, 909 fulfilled the study criteria (RBC + P = 391, RCP = 295, RBC = 223). RBC + P patients were older (mean age 42 vs 35 years for RCP and RBC), and 80% had a blunt injury (RCP = 52%, RBC = 56%). RCP and RBC + P were associated with lower odds of death at 24-h, compared to RBC alone (adjusted odds ratio [aOR] 0.69 [95%CI: 0.52; 0.92] and 0.60 [95%CI: 0.32; 1.13], respectively). The lower odds of death for RBC + P and RCP vs RBC were driven by penetrating injury (aOR 0.22 [95%CI: 0.10; 0.53] and 0.39 [95%CI: 0.20; 0.76], respectively). There was no association between RCP or RBC + P with 30-day survival vs RBC. CONCLUSION: Prehospital plasma transfusion for penetrating injury was associated with lower odds of death at 24-h compared to RBC alone. Large trials are needed to confirm these findings.

Traumatic coagulopathy in the older patient: analysis of coagulation profiles from the Activation of Coagulation and Inflammation in Trauma-2 (ACIT-2) observational, multicenter study.

BACKGROUND: Most studies describing traumatic coagulopathy have used data from patient cohorts with an average age of between 35 and 45 years. The last 10 years has seen a steep increase in the number of patients admitted with significant injury and bleeding who are older than the age of 65 years. Many coagulation protein levels alter significantly with normal aging, and it is possible that traumatic coagulopathy has a different signature with age. OBJECTIVES: The aim of this study was to report the coagulation profiles, including standard and extended laboratory, as well as viscoelastic hemostatic assays, stratified according to age to explore age-related differences in hemostatic capability. METHODS: In total, 1576 patients were analyzed from 6 European level 1 trauma centers. RESULTS: As age increased, there was evidence of higher fibrinogen, greater thrombin generation, greater clotting factor consumption, and greater activation of fibrinolysis. Despite this, shock and severe injury led to the same pattern of changes within age groups: lower procoagulant factors (including fibrinogen), increased fibrinolysis, and higher levels of activated protein C. Thromboelastography and rotational thromboelastometry tests detected traumatic coagulopathy with prolongation of R/clotting time and reductions in clot amplitudes in each age cohort. Advancing age strongly correlated with higher fibrinogen levels and greater fibrinolysis. CONCLUSION: Age-related coagulation changes are evident in injured patients. Broadly, similar patterns of coagulation abnormalities are seen across age groups following severe injury/shock, but thresholds for single clotting factors differ. Age-related differences may need to be considered when clinical treatments (eg, transfusion therapy) are indicated.

The CRYOSTAT2 trial: The rationale and study protocol for a multi-Centre, randomised, controlled trial evaluating the effects of early high-dose cryoprecipitate in adult patients with major trauma haemorrhage requiring major haemorrhage protocol activation.

OBJECTIVES: To describe the protocol for a multinational randomised, parallel, superiority trial, in which patients were randomised to receive early high-dose cryoprecipitate in addition to standard major haemorrhage protocol (MHP), or Standard MHP alone. BACKGROUND: Blood transfusion support for trauma-related major bleeding includes red cells, plasma and platelets. The role of concentrated sources of fibrinogen is less clear and has not been evaluated in large clinical trials. Fibrinogen is a key pro-coagulant factor that is essential for stable clot formation. A pilot trial had demonstrated that it was feasible to deliver cryoprecipitate as a source of fibrinogen within 90 min of admission. METHODS: Randomisation was via opaque sealed envelopes held securely in participating Emergency Departments or transfusion laboratories. Early cryoprecipitate, provided as 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g fibrinogen supplementation), was transfused as rapidly as possible, and started within 90 min of admission. Participants in both arms received standard treatment defined in the receiving hospital MHP. The primary outcome measure was all-cause mortality at 28 days. Symptomatic thrombotic events including venous thromboembolism and arterial thrombotic events (myocardial infarction, stroke) were collected from randomisation up to day 28 or discharge from hospital. EQ5D-5Land Glasgow Outcome Score were completed at discharge and 6 months. All analyses will be performed on an intention to treat basis, with per protocol sensitivity analysis. RESULTS: The trial opened for recruitment in June 2017 and the final patient completed follow-up in May 2022. DISCUSSION: This trial will provide firmer evidence to evaluate the effectiveness and cost-effectiveness of early high-dose cryoprecipitate alongside the standard MHP in major traumatic haemorrhage.

Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles.

Endotheliopathy following trauma is associated with poor outcome, but the underlying mechanisms are unknown. This study hypothesized that an increased extracellular vesicle (EV) concentration is associated with endotheliopathy after trauma and that red blood cell (RBC) transfusion could further enhance endotheliopathy. In this post hoc sub study of a multicentre observational trial, 75 trauma patients were stratified into three groups based on injury severity score or shock. In patient plasma obtained at hospital admission and after transfusion of four RBC transfusions, markers for endotheliopathy were measured and EVs were labelled with anti CD41 (platelet EVs), anti CD235a (red blood cell EVs), anti CD45 (leucocyte EVs), anti CD144 (endothelial EVs) or anti CD62e (activated endothelial EVs) and EV concentrations were measured with flow cytometry. Statistical analysis was performed by a Kruskall Wallis test with Bonferroni correction or Wilcoxon rank test for paired data. In patients with shock, syndecan-1 and von Willebrand Factor (vWF) were increased compared to patients without shock. Additionally, patients with shock had increased red blood cell EV and leucocyte EV concentrations compared to patients without shock. Endotheliopathy markers correlated with leucocyte EVs (ρ = 0.263, p = 0.023), but not with EVs derived from other cells. Injury severity score had no relation with EV release. RBC transfusion increased circulating red blood cell EVs but did not impact endotheliopathy. In conclusion, shock is (weakly) associated with EVs from leucocytes, suggesting an immune driven pathway mediated (at least in part) by shock.

Sex discrimination after injury: is inequity in tranexamic acid administration just the tip of the iceberg?

There is emerging evidence of inequalities in healthcare provision between women and men. Trauma care is no exception with a number of studies indicating lower levels of prioritisation for injured female patients. The antifibrinolytic drug tranexamic acid, reduced trauma deaths to a similar extent in females and males in the international Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH) randomised controlled trials, but in real-world practice, national registry data shows females are less likely to receive tranexamic acid than males. Inequity in the provision of tranexamic acid may extend beyond sex (and gender), and further study is required to examine the effect of age and mechanism of injury differences between men and women in the decision to treat.

Coagulopathy Underlying Rotational Thromboelastometry Derangements in Trauma Patients: A Prospective Observational Multicenter Study.

BACKGROUND: Viscoelastic hemostatic assays such as rotational thromboelastometry (ROTEM) are used to guide treatment of trauma induced coagulopathy. The authors hypothesized that ROTEM derangements reflect specific coagulation factor deficiencies after trauma. METHODS: This was a secondary analysis of a prospective cohort study in six European trauma centers in patients presenting with full trauma team activation. Patients with dilutional coagulopathy and patients on anticoagulants were excluded. Blood was drawn on arrival for measurement of ROTEM, coagulation factor levels, and markers of fibrinolysis. ROTEM cutoff values to define hypocoagulability were as follows: EXTEM clotting time greater than 80 s, EXTEM clot amplitude at 5 min less than 40 mm, EXTEM lysis index at 30 min less than 85%, FIBTEM clot amplitude at 5 min less than 10 mm, and FIBTEM lysis index at 30 min less than 85%. Based on these values, patients were divided into seven deranged ROTEM profiles and compared to the reference group (ROTEM values within reference range). The primary endpoint was coagulation factors levels and fibrinolysis. RESULTS: Of 1,828 patients, 732 (40%) had ROTEM derangements, most often consisting of a combined decrease in EXTEM and FIBTEM clot amplitude at 5 min, that was present in 217 (11.9%) patients. While an isolated EXTEM clotting time greater than 80 s had no impact on mortality, all other ROTEM derangements were associated with increased mortality. Also, coagulation factor levels in this group were similar to those of patients with a normal ROTEM. Of coagulation factors, a decrease was most apparent for fibrinogen (with a nadir of 0.78 g/l) and for factor V levels (with a nadir of 22.8%). In addition, increased fibrinolysis can be present when the lysis index at 30 min is normal but EXTEM and FIBTEM clot amplitude at 5 min is decreased. CONCLUSIONS: Coagulation factor levels and mortality in the group with an isolated clotting time prolongation are similar to those of patients with a normal ROTEM. Other ROTEM derangements are associated with mortality and reflect a depletion of fibrinogen and factor V. Increased fibrinolysis can be present when the lysis index after 30 min is normal.

Temporal Transitions in Fibrinolysis after Trauma: Adverse Outcome Is Principally Related to Late Hypofibrinolysis.

BACKGROUND: The relationship between late clinical outcomes after injury and early dynamic changes between fibrinolytic states is not fully understood. The authors hypothesized that temporal transitions in fibrinolysis states using rotational thromboelastometry (ROTEM) would aid stratification of adverse late clinical outcomes and improve understanding of how tranexamic acid modulates the fibrinolytic response and impacts mortality. METHODS: The authors conducted a secondary analysis of previously collected data from trauma patients enrolled into an ongoing prospective cohort study (International Standard Randomised Controlled Trial Number [ISRCTN] 12962642) at a major trauma center in the United Kingdom. ROTEM was performed on admission and at 24 h with patients retrospectively grouped into three fibrinolysis categories: tissue factor-activated ROTEM maximum lysis of less than 5% (low); tissue factor-activated ROTEM maximum lysis of 5 to 15% (normal); or tissue factor-activated ROTEM maximum lysis of more than 15% (high). Primary outcomes were multiorgan dysfunction syndrome and 28-day mortality. RESULTS: Seven-hundred thirty-one patients were included: 299 (41%) were treated with tranexamic acid and 432 (59%) were untreated. Two different cohorts with low-maximum lysis at 24 h were identified: (1) severe brain injury and (2) admission shock and hemorrhage. Multiple organ dysfunction syndrome was greatest in those with low-maximum lysis on admission and at 24 h, and late mortality was four times higher than in patients who remained normal during the first 24 h (7 of 42 [17%] vs. 9 of 223 [4%]; P = 0.029). Patients that transitioned to or remained in low-maximum lysis had increased odds of organ dysfunction (5.43 [95% CI, 1.43 to 20.61] and 4.85 [95% CI, 1.83 to 12.83], respectively). Tranexamic acid abolished ROTEM hyperfibrinolysis (high) on admission, increased the frequency of persistent low-maximum lysis (67 of 195 [34%]) vs. 8 of 79 [10%]; P = 0.002), and was associated with reduced early mortality (28 of 195 [14%] vs. 23 of 79 [29%]; P = 0.015). No increase in late deaths, regardless of fibrinolysis transition patterns, was observed. CONCLUSIONS: Adverse late outcomes are more closely related to 24-h maximum lysis, irrespective of admission levels. Tranexamic acid alters early fibrinolysis transition patterns, but late mortality in patients with low-maximum lysis at 24 h is not increased.

Use of a modified Delphi process to develop research priorities in major trauma.

PURPOSE: The burden of major trauma within the UK is ever increasing. There is a need to establish research priorities within the field. Delphi methodology can be used to develop consensus opinion amongst a group of stakeholders. This can be used to prioritise clinically relevant, patient-centred research questions to guide future funding allocations. The aim of our study was to identify key future research priorities pertaining to the management of major trauma in the UK. METHODS: A three-phased modified Delphi process was undertaken. Phase 1 involved the submission of research questions by members of the trauma community using an online survey (Phase 1). Phases 2 and 3 involved two consecutive rounds of prioritisation after questions were subdivided into 6 subcategories: Brain Injury, Rehabilitation, Trauma in Older People, Pre-hospital, Interventional, and Miscellaneous (Phases 2 and 3). Cut-off points were agreed by consensus amongst the steering subcommittees. This established a final prioritised list of research questions. RESULTS: In phase 1, 201 questions were submitted by 65 stakeholders. After analysis and with consensus achieved, 186 questions were taken forward for prioritisation in phase 2 with 114 included in phase 3. 56 prioritised major trauma research questions across the 6 categories were identified with a clear focus on long-term patient outcomes. Research priorities across the patient pathway from roadside to rehabilitation were deemed of importance. CONCLUSIONS: Consensus within the major trauma community has identified 56 key research questions across 6 categories. Dissemination of these questions to funding bodies to allow for the development of high-quality research is now required. There is a clear indication for targeted multi-centre multi-disciplinary research in major trauma.