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BACKGROUND: Trauma hemorrhage induces a coagulopathy with a high associated mortality rate. The Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (ITACTIC) randomized trial tested two goal-directed treatment algorithms for coagulation management, one guided by conventional coagulation tests and one by viscoelastic hemostatic assays (viscoelastic). The lack of a difference in 28-day mortality led us to hypothesize that coagulopathic patients received insufficient treatment to correct coagulopathy. METHODS: During ITACTIC, two sites were co-enrolling patients into an ongoing prospective observational study, which included serial blood sampling at the same intervals as in ITACTIC. The subgroup in both studies had conventional and viscoelastic test results for each patient available for analysis. A goal-directed treatment was defined as one triggered by an ITACTIC algorithm. Coagulopathy was defined as ROTEM EXTEM A5 <40mm. The primary outcome was correction of coagulopathy by the 12th unit of red blood cell transfusion during resuscitation. RESULTS: Full viscoelastic and conventional coagulation test results were available for 133 patients. 71% were coagulopathic on admission, and 16% developed a coagulopathy during resuscitation. ITACTIC VHA group patients were more likely to receive goal-directed treatment than the standard group (76% vs 47%, OR 3.73, 95%CI:1.64-8.49, p=0.002). However, only 54% of patients received goal-directed treatment, and only 20% corrected their coagulopathy (vs 0% with empiric treatment alone, not significant). Median time to first goal-directed treatment was 68(53-88) minutes for viscoelastic and 110(77-123) minutes for standard, p=0.005. CONCLUSION: In ITACTIC, many bleeding trauma patients did not receive an indicated goal-direct treatment. Interventions arrived late during resuscitation and were only partially effective at correcting coagulopathy.
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Importance: Hemorrhage is the most common cause of preventable death after injury. Most deaths occur early, in the prehospital phase of care. Objective: To establish whether prehospital zone 1 (supraceliac) partial resuscitative endovascular balloon occlusion of the aorta (Z1 P-REBOA) can be achieved in the resuscitation of adult trauma patients at risk of cardiac arrest and death due to exsanguination. Design, Setting, and Participants: This was a prospective observational cohort study (Idea, Development, Exploration, Assessment and Long-term follow-up [IDEAL] 2A design) with recruitment from June 2020 to March 2022 and follow-up until discharge from hospital, death, or 90 days evaluating a physician-led and physician-delivered, urban prehospital trauma service in the Greater London area. Trauma patients aged 16 years and older with suspected exsanguinating subdiaphragmatic hemorrhage, recent or imminent hypovolemic traumatic cardiac arrest (TCA) were included. Those with unsurvivable injuries or who were pregnant were excluded. Of 2960 individuals attended by the service during the study period, 16 were included in the study. Exposures: ZI REBOA or P-REBOA. Main Outcomes and Measures: The main outcome was the proportion of patients in whom Z1 REBOA and Z1 P-REBOA were achieved. Clinical end points included systolic blood pressure (SBP) response to Z1 REBOA, mortality rate (1 hour, 3 hours, 24 hours, or 30 days postinjury), and survival to hospital discharge. Results: Femoral arterial access for Z1 REBOA was attempted in 16 patients (median [range] age, 30 [17-76] years; 14 [81%] male; median [IQR] Injury Severity Score, 50 [39-57]). In 2 patients with successful arterial access, REBOA was not attempted due to improvement in clinical condition. In the other 14 patients (8 [57%] of whom were in traumatic cardiac arrest [TCA]), 11 successfully underwent cannulation and had aortic balloons inflated in Z1. The 3 individuals in whom cannulation was unsuccessful were in TCA (failure rate = 3/14 [21%]). Median (IQR) pre-REBOA SBP in the 11 individuals for whom cannulation was successful (5 [46%] in TCA) was 47 (33-52) mm Hg. Z1 REBOA plus P-REBOA was associated with a significant improvement in BP (median [IQR] SBP at emergency department arrival, 101 [77-107] mm Hg; 0 of 10 patients were in TCA at arrival). The median group-level improvement in SBP from the pre-REBOA value was 52 (95% CI, 42-77) mm Hg (P < .004). P-REBOA was feasible in 8 individuals (8/11 [73%]) and occurred spontaneously in 4 of these. The 1- and 3-hour postinjury mortality rate was 9% (1/11), 24-hour mortality was 27% (3/11), and 30-day mortality was 82% (9/11). Survival to hospital discharge was 18% (2/11). Both survivors underwent early Z1 P-REBOA. Conclusions and Relevance: In this study, prehospital Z1 P-REBOA is feasible and may enable early survival, but with a significant incidence of late death. Trial Registration: ClinicalTrials.gov Identifier: NCT04145271.
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Perioperative Care , Venous Thromboembolism , Wounds and Injuries , Humans , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Perioperative Care/methods , Perioperative Care/standards , Wounds and Injuries/complications , Europe , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Postoperative Complications/prevention & control , Postoperative Complications/etiologyABSTRACT
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.
Subject(s)
Abdominal Injuries , Wounds, Penetrating , Young Adult , Adolescent , Humans , Prospective Studies , Laparotomy/methods , Abdominal Injuries/surgery , Wounds, Penetrating/surgery , Retrospective Studies , Observational Studies as Topic , Multicenter Studies as TopicABSTRACT
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.
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Emergency Medical Services , Wounds and Injuries , Humans , Hemorrhage/etiology , Blood Coagulation , Emergency Service, Hospital , Wounds and Injuries/therapy , Wounds and Injuries/complicationsABSTRACT
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.
Subject(s)
Antifibrinolytic Agents , Tranexamic Acid , Venous Thromboembolism , Adult , Humans , Tranexamic Acid/therapeutic use , Antifibrinolytic Agents/therapeutic use , Venous Thromboembolism/chemically induced , Cohort Studies , Multiple Organ Failure , Hemorrhage/drug therapy , Hemorrhage/etiologyABSTRACT
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.
Subject(s)
Blood Coagulation Disorders , Shock, Hemorrhagic , Wounds and Injuries , Adult , Humans , Multiple Organ Failure/etiology , Hemorrhage/etiology , Blood Coagulation , Shock, Hemorrhagic/complications , Wounds and Injuries/complications , Wounds and Injuries/diagnosisABSTRACT
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.
Subject(s)
Blood Coagulation Disorders , Venous Thromboembolism , Adult , Humans , Child , Blood Coagulation Factors/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , Hemorrhage/drug therapy , Hemorrhage/etiology , Randomized Controlled Trials as TopicABSTRACT
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.
Subject(s)
Balloon Occlusion , Endovascular Procedures , Heart Arrest , Shock, Hemorrhagic , Humans , Aorta , Hemorrhage/therapy , Blood Pressure , Resuscitation/methods , Endovascular Procedures/methods , Shock, Hemorrhagic/therapy , Randomized Controlled Trials as TopicABSTRACT
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.
Subject(s)
Hemorrhage , Wounds, Penetrating , Adult , Male , Humans , Middle Aged , Female , Hemorrhage/therapy , Hemorrhage/drug therapy , Fibrinogen/adverse effects , Blood Transfusion , Blood Component TransfusionABSTRACT
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.
Subject(s)
Antifibrinolytic Agents , Tranexamic Acid , Wounds and Injuries , Male , Humans , Female , Aged , Tranexamic Acid/therapeutic use , Antifibrinolytic Agents/therapeutic use , Retrospective Studies , Hemorrhage/drug therapy , Emergency Service, Hospital , Bias , Wounds and Injuries/drug therapyABSTRACT
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.
Subject(s)
Afibrinogenemia , Blood Coagulation Disorders , Wounds and Injuries , Adult , Humans , Fibrinolysis , Afibrinogenemia/diagnosis , Thromboplastin , Prospective Studies , Thrombelastography/methods , Wounds and Injuries/complications , Wounds and Injuries/diagnosisABSTRACT
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.
Subject(s)
Blood Coagulation Disorders , Thrombelastography , Adult , Humans , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , Cohort Studies , Fibrinogen/analysis , Hemorrhage , Prognosis , ThromboplastinABSTRACT
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.
Subject(s)
Emergency Medical Services , Wounds and Injuries , Humans , Adult , Erythrocyte Transfusion , Blood Component Transfusion , Retrospective Studies , Plasma , Hemorrhage/therapy , Resuscitation , Erythrocytes , England , Wounds and Injuries/complications , Wounds and Injuries/therapyABSTRACT
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.
Subject(s)
Blood Coagulation Disorders , Hemostatics , Wounds and Injuries , Humans , Adult , Middle Aged , Blood Coagulation , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , Blood Coagulation Factors , Thrombelastography , Fibrinogen/metabolism , Inflammation , Hemostatics/pharmacology , Wounds and Injuries/complications , Wounds and Injuries/diagnosisABSTRACT
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.
Subject(s)
Fibrinogen , Hemorrhage , Humans , Adult , Hemorrhage/drug therapy , Fibrinogen/therapeutic use , Hospitalization , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
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.