ASGBI trauma committee position statement: a national audit of trauma laparotomy in the UK - an unmet need.

Patients who undergo laparotomy for major trauma are amongst the most critically unwell patients, and they have high morbidity and mortality rates. Despite 20 yr of improvements in resuscitation practices, those who present with hypotension continue to have mortality rates of up to 50%. Currently there is no mechanism for capturing national audit data on these patients, leading to their exclusion from potential quality improvement initiatives. We argue that there is an unmet need for quality assurance in this patient cohort and outline possible mechanisms to address this.

Platelets in Hemostasis, Thrombosis, and Inflammation After Major Trauma.

Trauma currently accounts for 10% of the total global burden of disease and over 5 million deaths per year, making it a leading cause of morbidity and mortality worldwide. Although recent advances in early resuscitation have improved early survival from critical injury, the mortality rate in patients with major hemorrhage approaches 50% even in mature trauma systems. A major determinant of clinical outcomes from a major injury is a complex, dynamic hemostatic landscape. Critically injured patients frequently present to the emergency department with an acute traumatic coagulopathy that increases mortality from bleeding, yet, within 48 to 72 hours after injury will switch from a hypocoagulable to a hypercoagulable state with increased risk of venous thromboembolism and multiple organ dysfunction. This review will focus on the role of platelets in these processes. As effectors of hemostasis and thrombosis, they are central to each phase of recovery from injury, and our understanding of postinjury platelet biology has dramatically advanced over the past decade. This review describes our current knowledge of the changes in platelet behavior that occur following major trauma, the mechanisms by which these changes develop, and the implications for clinical outcomes. Importantly, supported by research in other disease settings, this review also reflects the emerging role of thromboinflammation in trauma including cross talk between platelets, innate immune cells, and coagulation. We also address the unresolved questions and significant knowledge gaps that remain, and finally highlight areas that with the further study will help deliver further improvements in trauma care.

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.

Immature platelet dynamics are associated with clinical outcomes after major trauma.

BACKGROUND: Major trauma results in dramatic changes in platelet behavior. Newly formed platelets are more reactive than older platelets, but their contributions to hemostasis and thrombosis after severe injury have not been previously evaluated. OBJECTIVES: To determine how immature platelet metrics and plasma thrombopoietin relate to clinical outcomes after major injury. METHODS: A prospective observational cohort study was performed in adult trauma patients. Platelet counts and the immature platelet fraction (IPF) were measured at admission and 24 hours, 72 hours, and 7 days after injury. Thromboelastometry was performed at admission. Plasma thrombopoietin, c-Mpl, and GPIbα were quantified in a separate cohort. The primary outcome was in-hospital mortality; secondary outcomes were venous thromboembolic events and multiple organ dysfunction syndrome (MODS). RESULTS: On admission, immature platelet counts (IPCs) were significantly lower in nonsurvivors (n = 40) than in survivors (n = 236; 7.3 × 109/L vs 10.6 × 109/L; P = .009), but IPF did not differ. Similarly, impaired platelet function on thromboelastometry was associated with lower admission IPC (9.1 × 109/L vs 11.9 × 109/L; P < .001). However, at later time points, we observed significantly higher IPF and IPC in patients who developed venous thromboembolism (21.0 × 109/L vs 11.1 × 109/L; P = .02) and prolonged MODS (20.9 × 109/L vs 11 × 109/L; P = .003) than in those who did not develop complications. Plasma thrombopoietin levels at admission were significantly lower in nonsurvivors (P < .001), in patients with MODS (P < .001), and in those who developed venous thromboembolism (P = .04). CONCLUSION: Lower levels of immature platelets in the acute phase after major injury are associated with increased mortality, whereas higher immature platelet levels at later time points may predispose to thrombosis and MODS.

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.

Editor's Choice - Systematic Review and Meta-Analysis of Lower Extremity Vascular Complications after Arterial Access for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): An Inevitable Concern?

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporise non-compressible torso haemorrhage. Recent data have suggested that vascular access complications secondary to REBOA placement are higher than initially anticipated. This updated systematic review and meta-analysis aimed to determine the pooled incidence rate of lower extremity arterial complications after REBOA. DATA SOURCES: PubMed, Scopus, Embase, conference abstract listings, and clinical trial registries. REVIEW METHODS: Studies including more than five adults undergoing emergency REBOA for exsanguinating haemorrhage that reported access site complications were eligible for inclusion. A pooled meta-analysis of vascular complications was performed using the DerSimonian-Laird weights for the random effects model, presented as a Forest plot. Further meta-analyses compared the relative risk of access complications between different sheath sizes, percutaneous access techniques, and indications for REBOA. Risk of bias was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool. RESULTS: No randomised controlled trials were identified, and the overall study quality was poor. Twenty-eight studies including 887 adults were identified. REBOA was performed for trauma in 713 cases. The pooled proportion rate of vascular access complications was 8.6% (95% confidence interval 4.97 - 12.97), with substantial heterogeneity (I2 = 67.6%). There was no significant difference in the relative risk of access complications between 7 and > 10 F sheaths (p = .54), or between ultrasound guided and landmark guided access (p = .081). However, traumatic haemorrhage was associated with a significantly higher risk of complications compared with non-traumatic haemorrhage (p = .034). CONCLUSION: This updated meta-analysis aimed to be as comprehensive as possible considering the poor quality of source data and high risk of bias. It suggested that lower extremity vascular complications were higher than originally suspected after REBOA. While the technical aspects did not appear to impact the safety profile, a cautious association could be drawn between REBOA use for traumatic haemorrhage and a higher risk of arterial complications.

Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis.

BACKGROUND: Several current guidelines do not include antiplatelet use as an explicit indication for CT scan of the head following head injury. The impact of individual antiplatelet agent use on rates of intracranial haemorrhage is unclear. The primary objective of this systematic review was to assess if clopidogrel monotherapy was associated with traumatic intracranial haemorrhage (tICH) on CT of the head within 24 hours of presentation following head trauma compared with no antithrombotic controls. METHODS: Eligible studies were non-randomised studies with participants aged ≥18 years old with head injury. Studies had to have conducted CT of the head within 24 hours of presentation and contain a no antithrombotic control group and a clopidogrel monotherapy group.Eight databases were searched from inception to December 2020. Assessment of identified studies against inclusion criteria and data extraction were carried out independently and in duplicate by two authors.Quality assessment and risk of bias (ROB) were assessed using the Newcastle-Ottawa Quality Assessment tool and Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was conducted using a random-effects model and reported as an OR and 95% CI. RESULTS: Seven studies were eligible for inclusion with a total of 21 898 participants that were incorporated into the meta-analysis. Five studies were retrospective. Clopidogrel monotherapy was not significantly associated with an increase in risk of tICH compared with no antithrombotic controls (OR 0.97, 95% CI 0.54 to 1.75). Heterogeneity was high with an I2 of 75%. Sensitivity analysis produced an I2 of 21% and did not show a significant association between clopidogrel monotherapy and risk of tICH (OR 1.16, 95% CI 0.87 to 1.55). All studies scored for moderate to serious ROB on categories in the ROBINS-I tool. CONCLUSION: Included studies were vulnerable to confounding and several were small-scale studies. The results should be interpreted with caution given the ROB identified. This study does not provide statistically significant evidence that clopidogrel monotherapy patients are at increased risk of tICH after head injury compared with no antithrombotic controls. PROSPERO REGISTRATION NUMBER: CRD42020223541.

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.

Trauma Laparotomy in the UK: A Prospective National Service Evaluation.

BACKGROUND: Trauma patients requiring abdominal operation have considerable morbidity and mortality, yet no specific quality indicators are measured in the trauma systems of the UK. The aims of this study were to describe the characteristics and outcomes of patients undergoing emergency abdominal operation and key processes of care. STUDY DESIGN: A prospective multicenter service evaluation was conducted within all of the major trauma centers in the UK. The study was conducted during 6 months beginning in January 2019. Patients of any age undergoing laparotomy or laparoscopy within 24 hours of injury were included. Existing standards for related emergent conditions were used. RESULTS: The study included 363 patients from 34 hospitals. The majority were young men with no comorbidities who required operation to control bleeding (51%). More than 90% received attending-delivered care in the emergency department (318 of 363) and operating room (321 of 363). The overall mortality rate was 9%. Patients with blunt trauma had a greater risk of death compared with patients with penetrating injuries (16.6% vs 3.8%; risk ratio 4.3; 95% CI, 2.0 to 9.4). Patients in which the Major Hemorrhage Protocol (MHP) was activated and who received a blood transfusion (n = 154) constituted a high-risk subgroup, accounting for 45% of the study cohort but 97% of deaths and 96% of blood components transfused. The MHP subgroup had expedited timelines from emergency department arrival to knife to skin (MHP: median 119 minutes [interquartile range 64 to 218 minutes] vs no MHP: median 211 minutes [interquartile range 135 to 425 minutes]; p < 0.001). CONCLUSIONS: The majority of trauma patients requiring emergency abdominal operation received a high standard of expedited care in a maturing national trauma system. Despite this, mortality and resource use among high-risk patients remains considerable.

Bouveret syndrome: a rare cause of gastric outlet obstruction.

Bouveret syndrome is a rare cause of gastric outlet obstruction. It is characterised by the presence of an obstructing gallstone in the pylorus or proximal duodenum, which has travelled to its obstructing position via an acquired fistula. Our case involves a 73-year-old man presenting to the acute surgical take with a 2-day history of right-sided abdominal pain and vomiting. His medical history included perforated cholecystitis treated with antibiotics and percutaneous gall bladder drainage, 1 year earlier. Examination and blood tests were suggestive of gastric outlet obstruction. CT abdomen and pelvis demonstrated a large gallstone obstructing the duodenum, confirming a diagnosis of Bouveret syndrome. The patient improved following gastrolithotomy, and was discharged 2 weeks postoperatively. Fistula formation is a complication of chronic cholecystitis and therefore Bouveret syndrome should be considered in patients with a background of gallstone disease presenting with gastric outlet obstruction.

Resolvin D1 Attenuates the Organ Injury Associated With Experimental Hemorrhagic Shock.

OBJECTIVE: To evaluate the potential changes in the plasma levels of resolvin D1 (RvD1) in patients with trauma and hemorrhage. Having found that trauma results in a profound reduction in plasma RvD1 in patients, we have then investigated the effects of RvD1 on the organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat. BACKGROUND: HS is a common cause of death in trauma due to excessive systemic inflammation and multiple organ failure. RvD1 is a member of the resolvin family of pro-resolution mediators. METHODS: Blood samples were drawn from critically injured patients (n = 27, ACITII-prospective observational cohort study) within 2 hours of injury for targeted liquid chromatography tandem mass spectrometry. HS rats (removal of blood to reduce arterial pressure to 30 ±â€Š2 mm Hg, 90 minutes, followed by resuscitation) were treated with RvD1 (0.3 or 1 µg/kg intravenous (i.v.)) or vehicle (n = 7). Parameters of organ injury and dysfunction were determined. RESULTS: Plasma levels of RvD1 (mg/dL) were reduced in patients with trauma+HS (0.17 ±â€Š0.08) when compared with healthy volunteers (0.76 ±â€Š0.25) and trauma patients (0.62 ±â€Š0.20). In rats with HS, RvD1 attenuated the kidney dysfunction, liver injury, and tissue ischemia. RvD1 also reduced activation of the nuclear factor (NF)-κB pathway and reduced the expression of pro-inflammatory proteins such as inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1ß, and interleukin-6. CONCLUSION: Plasma RvD1 is reduced in patients with trauma-HS. In rats with HS, administration of synthetic RvD1 on resuscitation attenuated the multiple organ failure associated with HS by a mechanism that involves inhibition of the activation of NF-κB.

Alterations in platelet behavior after major trauma: adaptive or maladaptive?

Platelets are damage sentinels of the intravascular compartment, initiating and coordinating the primary response to tissue injury. Severe trauma and hemorrhage induce profound alterations in platelet behavior. During the acute post-injury phase, platelets develop a state of impaired ex vivo agonist responsiveness independent of platelet count, associated with systemic coagulopathy and mortality risk. In patients surviving the initial insult, platelets become hyper-responsive, associated with increased risk of thrombotic events. Beyond coagulation, platelets constitute part of a sterile inflammatory response to injury: both directly through release of immunomodulatory molecules, and indirectly through modifying behavior of innate leukocytes. Both procoagulant and proinflammatory aspects have implications for secondary organ injury and multiple-organ dysfunction syndromes. This review details our current understanding of adaptive and maladaptive alterations in platelet biology induced by severe trauma, mechanisms underlying these alterations, potential platelet-focused therapies, and existing knowledge gaps and their research implications.

Loss of GPVI and GPIbα contributes to trauma-induced platelet dysfunction in severely injured patients.

Trauma-induced coagulopathy (TIC) is a complex, multifactorial failure of hemostasis that occurs in 25% of severely injured patients and results in a fourfold higher mortality. However, the role of platelets in this state remains poorly understood. We set out to identify molecular changes that may underpin platelet dysfunction after major injury and to determine how they relate to coagulopathy and outcome. We performed a range of hemostatic and platelet-specific studies in blood samples obtained from critically injured patients within 2 hours of injury and collected prospective data on patient characteristics and clinical outcomes. We observed that, although platelet counts were preserved above critical levels, circulating platelets sampled from trauma patients exhibited a profoundly reduced response to both collagen and the selective glycoprotein VI (GPVI) agonist collagen-related peptide, compared with those from healthy volunteers. These responses correlated closely with overall clot strength and mortality. Surface expression of the collagen receptors GPIbα and GPVI was reduced on circulating platelets in trauma patients, with increased levels of the shed ectodomain fragment of GPVI detectable in plasma. Levels of shed GPVI were highest in patients with more severe injuries and TIC. Collectively, these observations demonstrate that platelets experience a loss of GPVI and GPIbα after severe injury and translate into a reduction in the responsiveness of platelets during active hemorrhage. In turn, they are associated with reduced hemostatic competence and increased mortality. Targeting proteolytic shedding of platelet receptors is a potential therapeutic strategy for maintaining hemostatic competence in bleeding and improving the efficacy of platelet transfusions.

Histone H4 induces platelet ballooning and microparticle release during trauma hemorrhage.

Trauma hemorrhage is a leading cause of death and disability worldwide. Platelets are fundamental to primary hemostasis, but become profoundly dysfunctional in critically injured patients by an unknown mechanism, contributing to an acute coagulopathy which exacerbates bleeding and increases mortality. The objective of this study was to elucidate the mechanism of platelet dysfunction in critically injured patients. We found that circulating platelets are transformed into procoagulant balloons within minutes of injury, accompanied by the release of large numbers of activated microparticles which coat leukocytes. Ballooning platelets were decorated with histone H4, a damage-associated molecular pattern released in massive quantities after severe injury, and exposure of healthy platelets to histone H4 recapitulated the changes in platelet structure and function observed in trauma patients. This is a report of platelet ballooning in human disease and of a previously unrecognized mechanism by which platelets contribute to the innate response to tissue damage.

What's new for trauma haemorrhage management?

Uncontrolled haemorrhage is the leading cause of preventable death from injury and is a major contributor to the global burden of disease. The majority of deaths resulting from bleeding occur within the first 3 hours of hospital admission, and the window for meaningful intervention is therefore extremely small. Resuscitative efforts during active bleeding should focus on maintaining haemostatic function with blood product transfusion and early administration of tranexamic acid. Achieving control of haemorrhage is the overarching treatment priority and may require temporising measures before definitive surgical or radiological intervention. This review summarizes the contemporary approaches to resuscitation of bleeding trauma patients, options for achieving haemorrhage control, and current areas of active research including organ protective resuscitation and suspended animation.

The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients.

OBJECTIVE: To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. BACKGROUND: Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent. METHODS: A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry [ROTEM]) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels. RESULTS: Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5-15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived: 103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = -0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo. CONCLUSIONS: Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell surface plasminogen receptor which may drive the hyperfibrinolysis in these patients and which when shed artificially lowers %ML ex-vivo.