The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition.

BACKGROUND: Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. METHODS: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. RESULTS: This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. CONCLUSION: A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Further improvement in outcomes will be achieved by optimising and standardising trauma care in line with the available evidence across Europe and beyond.

Detection of Acute Traumatic Coagulopathy by Viscoelastic Haemostatic Assays Compared to Standard Laboratory Tests: A Systematic Review.

Introduction: The aim of this systematic review was to investigate whether viscoelastic haemostatic assays (VHAs) offer comparative diagnostic ability of acute traumatic coagulopathy (ATC) compared to the standard laboratory coagulation tests (SLCT). ATC is a complication of major trauma characterized by dysfunctional blood clotting, leading to an increased bleeding risk. Additionally, we aimed to analyse the association of VHA with blood product use and health outcomes. Methods: The search protocol was pre-published and completed on December 2, 2020, assessing manuscripts from 2000 until the present. We searched MEDLINE, Embase, Cochrane Central, BIOSIS, Emcare, CINAHL, and additional online resources and referenced lists. Included were manuscripts that quantitatively reported the detection of ATC using VHAs and SLCTs. A meta-analysis was undertaken including observational studies that reported on patients with injuries to all body regions and results analysed using a random-effects model and reported using pooled odds ratio with 95% confidence intervals (CI). Results: There were 14 observational studies and one randomized control trial involving 2,715 participants that satisfied inclusion criteria. We observed significant heterogeneity in the definitions of ATC, study design, setting, and patient population. Among observational studies that reported on patients with injuries to all body regions, VHAs were associated with higher odds of diagnosing ATC compared to SLCT (pooled OR 2.4; 95% CI: 1.4-4.1). There was inadequate evidence to suggest VHAs were associated with reduced blood product usage or lower mortality. Conclusion: VHAs detected more patients with ATC compared to SLCTs. However, the clinical significance and applicability of this finding remains unknown as translation to management was not adequately reported.

Early Identification of Acute Traumatic Coagulopathy Using Clinical Prediction Tools: A Systematic Review.

: Background and objectives: Prompt identification of patients with acute traumatic coagulopathy (ATC) is necessary to expedite appropriate treatment. An early clinical prediction tool that does not require laboratory testing is a convenient way to estimate risk. Prediction models have been developed, but none are in widespread use. This systematic review aimed to identify and assess accuracy of prediction tools for ATC. Materials and Methods: A search of OVID Medline and Embase was performed for articles published between January 1998 and February 2018. We searched for prognostic and predictive studies of coagulopathy in adult trauma patients. Studies that described stand-alone predictive or associated factors were excluded. Studies describing prediction of laboratory-diagnosed ATC were extracted. Performance of these tools was described. Results: Six studies were identified describing four different ATC prediction tools. The COAST score uses five prehospital variables (blood pressure, temperature, chest decompression, vehicular entrapment and abdominal injury) and performed with 60% sensitivity and 96% specificity to identify an International Normalised Ratio (INR) of >1.5 on an Australian single centre cohort. TICCS predicted an INR of >1.3 in a small Belgian cohort with 100% sensitivity and 96% specificity based on admissions to resuscitation rooms, blood pressure and injury distribution but performed with an Area under the Receiver Operating Characteristic (AUROC) curve of 0.700 on a German trauma registry validation. Prediction of Acute Coagulopathy of Trauma (PACT) was developed in USA using six weighted variables (shock index, age, mechanism of injury, Glasgow Coma Scale, cardiopulmonary resuscitation, intubation) and predicted an INR of >1.5 with 73.1% sensitivity and 73.8% specificity. The Bayesian network model is an artificial intelligence system that predicted a prothrombin time ratio of >1.2 based on 14 clinical variables with 90% sensitivity and 92% specificity. Conclusions: The search for ATC prediction models yielded four scoring systems. While there is some potential to be implemented effectively in clinical practice, none have been sufficiently externally validated to demonstrate associations with patient outcomes. These tools remain useful for research purposes to identify populations at risk of ATC.

An increased tendency in fibrinogen activity and its association with a hypo-fibrinolytic state in early stages after injury in patients without acute traumatic coagulopathy (ATC).

Acute traumatic coagulopathy (ATC) diagnosed by prolongation of APTT and/or PT/INR involves alterations in platelet activity, coagulation and fibrinolysis. However, data showing the haemostatic situation in injured patients without ATC are scarce. To assess whether haemostatic impairment is also present in injured patients without ATC, ten injured patients without ATC and ten normal individuals were examined. The patients were sampled on arrival at the emergency department 0, 2, 12 h after surgical or other intervention. Thrombin generation, fibrin formation and fibrin proteolysis were determined via several laboratory methods, using tissue factor as the coagulation trigger. Thrombograms demonstrated that trauma accelerated both thrombin generation and decay. In the presence of unaffected peak thrombin levels, these two contradictory effects cancelled each other out, leading to the global endogenous thrombin potential (ETP) remaining normal. Under the mediation of normal ETP, fibrin network permeability (Ks) kept the reference levels in the two groups of subjects. Fibrinogen (FBG) activity (Clauss) rose with time from 0 to 2 h and 12 h, which significantly slowed down Clot Lysis Potential as determined by an in vitro method with exogenous t-PA. SUMMARY: the main haemostatic impairment in the present patients concerned an increased tendency in FBG activity. Since an increase in FBG is a biomarker of acute inflammation and also predicts greater fibrin production which down-regulates fibrinolysis, we suggest that during early stages after injury, patients without ATC may suffer from worsening inflammation and confront enhancement of thrombosis risk due to dysfunction of fibrinolysis.

Evaluation for effects of severe acidosis on hemostasis in trauma patients using thrombelastography analyzer.

OBJECTIVE: To investigate effects of metabolic acidosis on hemostasis function in trauma patients using thromboelastography analyzer. METHODS: 65 critically injured patients and 19 healthy volunteers were enrolled in the study. Three samples of whole blood were collected from each patient or healthy volunteer. These three samples were acidified with 50mmol/l phosphate-buffered saline (PBS) (pH5.8) or a neutral buffer (50mmol/l phosphate, pH7.4) and acidified blood sample with target pH of 6.95, 7.15 or 7.35 was obtained respectively. These three samples with target pH value were added into thrombelastography analyzer (TEG® 5000 Thrombelastograph Hemostasis Analyzers; Haemoscope Corporation, Niles, Illinois, USA) respectively and variables of Clot time (r), Rate of clot formation (α Angle), Clot formation time (K), Coagulation Index (CI) and Maximum strength (MA) were monitored at 37°C. Besides, association between TEG® parameters and clinicopathological features was analyzed by the Pearson χ2 test. RESULTS: In trauma patients, all 5 thrombelastographic variables, Clot time (r), Clot formation time (K), Maximum Amplitude (MA), Rate of clot formation (α Angle) and Coagulation Index (CI), were significantly affected by blood acidification, F(1.321,83.213)=88.960, P<0.001, F(2,128)=112.738, P<0.001, F(1.199,76.748)=37.964, P<0.001, F(1.195,76.452)=16.789, P<0.001 and F(2,128)=178.674, P<0.001. Post hoc tests showed that moderate acidosis (pH7.15) significantly elongated K time (from 2.6 to 3.4min, P=0.0013) and increased α Angle (from 51.9°to 52.2°, P=0.0040). r, MA and CI were not markedly influenced under moderate acidification. Comparing to mild acidosis (pH7.15), severe acidosis (pH6.95) induced more serious impairment to hemostasis and all 5 variables was substantially affected, r (from 5.9 to 6.8min, P<0.001), K (from 3.4 to 3.9min, P<0.001), α Angle (from 52.2°to 50.8°, P=0.002), MA (from 52.9 to 51.6mm, P<0.001) and CI (from -2.3 to -4.2, P<0.001). Additionally, higher r elongation under severe acidosis was significantly associated with an increased mortality rate and transfusion requirement (P=0.019 and 0.031). In healthy volunteers, similar effects on hemostasis were detected. Inhibition ratios of thrombelastographic parameters were significantly higher in trauma patients than in healthy volunteers indicating severer impairment of metabolic acidosis to hemostasis in critically injured patients. CONCLUSIONS: The degree of metabolic acidosis in trauma patients is positively correlated to the severity of hemostasis dysfunction. Additionally, acidosis induces more serious impairment to hemostasis in trauma patients than in healthy volunteers. Moreover, acidosis-induced r time elongation is positively related to a higher death rate and increased transfusion requirement and this indicates a predictive role of TEG® variables for prognosis of traumatized patients.

Development and validation of a prehospital prediction model for acute traumatic coagulopathy.

BACKGROUND: Acute traumatic coagulopathy (ATC) is a syndrome of early, endogenous clotting dysfunction that afflicts up to 30% of severely injured patients, signaling an increased likelihood of all-cause and hemorrhage-associated mortality. To aid identification of patients within the likely therapeutic window for ATC and facilitate study of its mechanisms and targeted treatment, we developed and validated a prehospital ATC prediction model. METHODS: Construction of a parsimonious multivariable logistic regression model predicting ATC - defined as an admission international normalized ratio >1.5 - employed data from 1963 severely injured patients admitted to an Oregon trauma system hospital between 2008 and 2012 who received prehospital care but did not have isolated head injury. The prediction model was validated using data from 285 severely injured patients admitted to a level 1 trauma center in Seattle, WA, USA between 2009 and 2013. RESULTS: The final Prediction of Acute Coagulopathy of Trauma (PACT) score incorporated age, injury mechanism, prehospital shock index and Glasgow Coma Score values, and prehospital cardiopulmonary resuscitation and endotracheal intubation. In the validation cohort, the PACT score demonstrated better discrimination (area under the receiver operating characteristic curve 0.80 vs. 0.70, p = 0.032) and likely improved calibration compared to a previously published prehospital ATC prediction score. Designating PACT scores ≥196 as positive resulted in sensitivity and specificity for ATC of 73% and 74%, respectively. CONCLUSIONS: Our prediction model uses routinely available and objective prehospital data to identify patients at increased risk of ATC. The PACT score could facilitate subject selection for studies of targeted treatment of ATC.

The challenge in management of hemorrhagic shock in trauma.

Transfusion and resuscitation practices in trauma have undergone a sea change over the past decade. New understanding of transfusion physiology and experiences in military trauma over the last decade has identified key factors taken as challenges in trauma. The most important challenge remains acute traumatic coagulopathy (ATC) which sets in early after a trauma and spirals the patient into shock and continued bleeding. World wide trauma is the leading cause of mortality. More than 6 million deaths occur due to trauma out of which 20% are due to uncontrollable bleeding. Out of the hospital admissions in trauma 20% develop coagulopathy. Mortality is three to four times higher in a patient with coagulopathy and thus prevention and correction of coagulopathy is the central goal of the management of hemorrhagic shock in trauma. Damage control resuscitation (DCR), a strategy combining the techniques of permissive hypotension, hemostatic resuscitation and damage control surgery has been widely adopted as the preferred method of resuscitation in patients with haemorrhagic shock. The over-riding goals of DCR are to mitigate metabolic acidosis, hypothermia and coagulopathy, This article looks at the importance of acute traumatic coagulopathy, its etiology, diagnosis, effects and resuscitation strategies to prevent it and to see the background behind this shift.

Association between lung contusion volume and acute changes in fibrinogen levels: A single-center observational study.

Aim: Organ tissue damage, including the lungs, may lead to acute coagulopathy. This study aimed to evaluate the association between lung contusion volume and serum fibrinogen level during the acute phase of trauma. Methods: We conducted an observational study using electronic medical records at a tertiary-care center between January 2015 and December 2018. We included patients with lung contusions on hospital arrival. We used three-dimensional computed tomography to calculate lung contusion volumes. The primary outcome was the lowest fibrinogen level measured within 24 h of hospital arrival. We evaluated the association between lung contusion volume and outcome with multivariable linear regression analysis. Also, we calculated the sensitivity and specificity of lung contusion volume in patients with a serum fibrinogen level of ≤150 mg/dL. Results: We identified 124 eligible patients. Their median age was 43.5 years, and 101 were male (81.5%). The median lung contusion volume was 10.9%. The median lowest fibrinogen level within 24 h from arrival was 188.0 mg/dL. After adjustment, lung contusion volume had a statistically significant association with the lowest fibrinogen level within 24 h from arrival (coefficient -1.6, 95% confidence interval -3.16 to -0.07). When a lung contusion volume of 20% was used as the cutoff, the sensitivity and specificity to identify fibrinogen depletion were 0.27 and 0.95, respectively. Conclusion: Lung contusion volume was associated with the lowest fibrinogen level measured within 24 h from hospital arrival. Measuring lung contusion volume may help to identify patients with a progression of fibrinogen depletion.

Prospective evaluation of platelet function and fibrinolysis in 20 dogs with trauma.

OBJECTIVES: To determine platelet function and assess fibrinolysis in dogs following trauma using multiple electrical impedance aggregometry and a modified thromboelastographic (TEG) technique. To determine if the severity of trauma, as assessed by the Animal Trauma Triage (ATT) score and clinicopathological markers of shock, is associated with a greater degree of platelet dysfunction and fibrinolysis. SETTING: University teaching hospital. ANIMALS: Twenty client-owned dogs with trauma (occurring <24 h prior to admission and blood sampling) and ATT score of >4 were prospectively recruited. A control group of 10 healthy dogs was included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Platelet function was measured using multiple electrode platelet aggregometry (MEPA) utilizing arachidonic acid, ADP, and collagen agonists. Fibrinolysis was assessed in citrated whole blood with the addition of tissue plasminogen activator (tPA; 50 U/mL) using kaolin-activated TEG. Conventional statistical analysis was performed to compare coagulation parameters between the groups and assess linear correlations. Median (interquartile range) ATT score was 5 (5-7), and 65% (n = 13) of dogs suffered polytrauma. Mean (± SD) time from trauma to blood sampling was 9 hours (± 6). Median (interquartile range) shock index and plasma lactate concentration were 1.1 (0.7-2.0, n = 16) and 2.9 mmol/L (0.9-16.0, n = 18), respectively. Four dogs did not survive to discharge (20%). There were no differences between the trauma and control group coagulation variables. A moderate negative correlation between ATT score and area under the curve for ADP was found (P = 0.043, r2  = -0.496). CONCLUSIONS: Preliminary evaluation of platelet function measured by MEPA, and fibrinolysis measured by tPA-modified TEG, is not significantly different in this population of dogs with traumatic injury compared to healthy dogs.

[Traumatic hemipelvectomy : An uncommon case in trauma surgery]. / Traumatische Hemipelvektomie : Ein nichtalltäglicher Fall in der Unfallchirurgie.

The challenge in treating traumatic hemipelvectomy is the dynamics of the complex and life-threatening consequences of the injury. These include skin and soft tissue defects, osseous, neural and vascular injuries as well as the subsequent hemostatic derangement and organ dysfunction as part of the shock process. The treatment requires rapid and targeted decisions to save the patient's life. In this particular case a 34-year-old farmer was trapped between a wheeled loader and a stationary trailer. Upon arrival at the hospital the patient was in a state of hemorrhagic shock with accompanying acute traumatic coagulopathy and a grade III open pelvic trauma with complete ischemia of the left leg and a bladder injury. After performing emergency surgery and a two-stage approach for pelvic stabilization the patient's condition deteriorated up to multiorgan failure, necessitating left-sided hemipelvectomy as an immediate life-saving salvage procedure. In the further course multiple revision surgeries and plastic reconstructions due to wound infections and the presence of skin and soft tissue damage were required. Due to the rare confrontation with this type of injury in everyday practice and the absence of a universal treatment algorithm, the following case report is intended to contribute to a better understanding of the treatment and to illustrate the coherent interactions of the individual organ systems affected.

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.

Pathophysiology of hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is a common condition that may lead to hemodynamic instability, decreased oxygen delivery, cellular hypoxia, organ damage, and ultimately death. CLINICAL IMPORTANCE: This review addresses the pathophysiology of hemorrhagic shock. Hemorrhagic shock can be rapidly fatal and is the leading cause of death in human trauma patients. Understanding the pathophysiology of hemorrhagic shock is imperative in understanding the current hemostatic and resuscitative strategies and is foundational to the development of new therapeutic options. KEY POINTS: Shock is a state of inadequate cellular energy production and can be triggered by many causes Both traumatic and non-traumatic causes of hemorrhage can lead to the development of hemorrhagic shock Prompt recognition and attenuation of hemorrhage is paramount in preventing the onset or potentiation of hemorrhagic shock Acute hemorrhage produces distinct physiological responses depending on the magnitude and rate of hemorrhage. Hemorrhagic shock may be directly related to the initial injury but may also be exacerbated and complicated by a post-traumatic coagulopathy, termed acute traumatic coagulopathy.

Integrated single-cell multiomics reveals novel immune candidate markers for post-traumatic coagulopathy.

Introduction: Post-traumatic coagulopathy (PTC) is a critical pathology in traumatic brain injury (TBI), however, its potential mechanism is not clear. To explore this in peripheral samples, we integrated single cell RNA-sequencing and T cell repertoire (TCR)-sequencing across a cohort of patients with TBI. Methods: Clinical samples from patients with more brain severity demonstrated overexpression of T cell receptor-encoding genes and less TCR diversity. Results: By mapping TCR clonality, we found patients with PTC have less TCR clones, and the TCR clones are mainly distributed in cytotoxic effector CD8+T cell. In addition, the counts of CD8+ T cell and natural killer (NK) cells are associated with the coagulation parameter by WGCNA, and the granzyme and lectin-like receptor profiles are also decreased in the peripheral blood from TBI patients, suggesting that reduced peripheral CD8+ clonality and cytotoxic profiles may be involved in PTC after TBI. Conclusion: Our work systematically revealed the critical immune status in PTC patients at the single-cell level.

Efficacy and safety of fibrinogen administration in acute post-traumatic hypofibrinogenemia in isolated severe traumatic brain injury: A randomized clinical trial.

AIM: This study was conducted to evaluate clinical outcomes after fibrinogen administration in hypofibrinogenemia following severe traumatic brain injury. BACKGROUND: Post traumatic coagulopathy (PTC) is a common but devastating medical condition in patients with severe head injury. Hypofibrinogenemia is considered as an indicator for poor clinical outcomes in traumatic brain injury (TBI). METHODS: In this randomized clinical trial (RCT), primarily 137 patients with severe traumatic brain injury (Glasgow coma scale score: GCS < 9) were enrolled. Thereafter, their plasma fibrinogen level was measured. The patients with primary hypofibrinogenemia (<200 mg/dL) with no concurrent coagulopathy were randomly allocated into fibrinogen-receiving (n = 50) and control (n = 54) groups. P-value < 0.05 was considered as statistically significant. RESULTS: Seventy-one patients were analyzed in the final step of the study. The mean value for age in fibrinogen and control groups was 25.64 ± 10.71 and 28.91 ± 12.25 years old, respectively. Male - female patients in both groups were equally distributed. In the fibrinogen receiving group, GCS scores were significantly higher after 24, 48, and 72 h compared to the control group (p = 0.000). Hematoma expansion was better controlled in the fibrinogen receiving group (p = 0.000). Notably, the number needed to treat (NNT) for fibrinogen infusion and hematoma expansion control was 2.3. Glasgow outcome scale-extended (GOSE) was significantly better in the fibrinogen group (p = 0.25). Multiple regression tests showed intracerebral hematoma (ICH) and severe brain edema had the most detrimental effect on GOSE outcomes. The need for cranial surgery, hospital stay duration, mechanical ventilator dependency, in hospital and 90-day post discharge mortality rates were similar in both study groups. CONCLUSION: In severe TBI, hypofibrinogenemia correction (>200 mg/dL) could improve GOSE, GCS score progression within 3 days after primary head injury and hematoma expansion controllability.

Hemostatic Strategies in Trauma.

Bleeding is a leading cause of early death from trauma. Consequently, effective hemostasis can improve the odds of survival after severe traumatic injury. Understanding the pathophysiology of trauma-induced coagulopathy can provide insights into effective strategies to assess and halt hemorrhage. Both physical assessment and appropriate laboratory studies are important in the diagnosis and evaluation of coagulopathy to identify the most effective mechanical and pharmacological strategies to achieve hemostasis. This article uses a case study approach to explore evidence-based techniques to evaluate hemorrhage and strategies to promote hemostasis.

Four-factor prothrombin complex concentrate to reduce allogenic blood product transfusion in patients with major trauma, the PROCOAG trial: study protocol for a randomized multicenter double-blind superiority study.

BACKGROUND: Optimal management of severe trauma patients with active hemorrhage relies on adequate initial resuscitation. Early administration of coagulation factors improves post-traumatic coagulation disorders, and four-factor prothrombin complex concentrate (PCC) might be useful in this context. Our main hypothesis is that four-factor PCC in addition to a massive transfusion protocol decreases blood product consumption at day 1 in severe trauma patients with major bleeding. METHODS: This is a prospective, randomized, multicenter, double-blind, parallel, controlled superiority trial. Eligible patients are trauma patients with major bleeding admitted to a French level-I trauma center. Patients randomized in the treatment arm receive 1 mL/kg (25 IU/ml of Factor IX/Kg) four-factor PCC within 1-h post-admission while patients randomized in the controlled group receive 1 mL/kg of saline solution 0.9% as a placebo. Treatments are given as soon as possible using syringe pumps (120 mL/h). The primary endpoint is the amount of blood products transfused in the first 24 h post-admission (including red blood cells, frozen fresh plasma, and platelets). The secondary endpoints are the amount of each blood product transfused in the first 24 h, time to achieve prothrombin time ratio < 1.5, time to hemostasis, number of thrombo-embolic events at 28 days, mortality at 24 h and 28 days, number of intensive care unit-free days, number of ventilator-free days, number of hospital-free days within the first 28 days, hospitalization status at day 28, Glasgow outcome scale extended for patients with brain lesions on initial cerebral imaging, and cost of each strategy at days 8 and 28. Inclusions have started in December 2017 and are expected to be complete by June 2021. DISCUSSION: If PCC reduces total blood consumption at day 1 after severe trauma, this therapy, in adjunction to a classic massive transfusion protocol, may be used empirically on admission in patients at risk of massive transfusion to enhance coagulation. Moreover, this treatment may decrease blood product-related complications and may improve clinical outcomes after post-traumatic hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT03218722 . Registered on July 14, 2017.

The role of cryoprecipitate in human and canine transfusion medicine.

OBJECTIVE: To evaluate the current role of cryoprecipitate in human and canine transfusion medicine. DATA SOURCES: Human and veterinary scientific reviews and original studies found using PubMed and CAB Abstract search engines were reviewed. HUMAN DATA SYNTHESIS: In the human critical care setting, cryoprecipitate is predominantly used for fibrinogen replenishment in bleeding patients with acute traumatic coagulopathy. Other coagulopathic patient cohorts for whom cryoprecipitate is recommended include those undergoing cardiovascular or obstetric procedures or patients bleeding from advanced liver disease. Preferential selection of cryoprecipitate versus fibrinogen concentrate (when available) is currently being investigated. Also a matter of ongoing debate is whether to administer this product as part of a fixed-dose massive hemorrhage protocol or to incorporate it into a goal-directed transfusion algorithm applied to the individual bleeding patient. VETERINARY DATA SYNTHESIS: Although there are sporadic reports of the use of cryoprecipitate in dogs with heritable coagulopathies, there are few to no data pertaining to its use in acquired hypofibrinogenemic states. Low fibrinogen in dogs (as in people) has been documented with acute traumatic coagulopathy, advanced liver disease, and disseminated intravascular coagulation. Bleeding secondary to these hypocoagulable states may be amenable to cryoprecipitate therapy. Indications for preferential selection of cryoprecipitate (versus fresh frozen plasma) remain to be determined. CONCLUSIONS: In the United States, cryoprecipitate remains the standard of care for fibrinogen replenishment in the bleeding human trauma patient. Its preferential selection for this purpose is the subject of several ongoing human clinical trials. Timely incorporation of cryoprecipitate into the transfusion protocol of the individual bleeding patient with hypofibrinogenemia may conserve blood products, mitigate adverse transfusion-related events, and improve patient outcomes. Cryoprecipitate is readily available, effective, and safe for use in dogs. The role of this blood product in clinical canine patients with acquired coagulopathy remains unknown.

Early prediction of acute traumatic coagulopathy: a validation of the COAST score using the German Trauma Registry.

BACKGROUND: Early identification of trauma patients at risk of developing acute traumatic coagulopathy (ATC) is important for initiating appropriate, coagulopathy-focused treatment. A clinical ATC prediction tool is a quick, simple method to evaluate risk. The COAST score was developed and validated in Australia but is yet to be validated on a European population. We validated the ability of the COAST score to predict coagulopathy and adverse bleeding-related outcomes on a large European trauma population. METHODS: The COAST score was modified and applied to a retrospective cohort of trauma patients from the German Trauma Registry (TR-DGU). The primary outcome was coagulopathy defined as INR > 1.5 or aPTT > 60 s. Secondary outcomes were massive transfusion, blood product requirements, urgent surgery and mortality. The cohort included adult trauma patients with Injury Severity Score > 15 treated in Germany/Austria in 2012-2016. RESULTS: 15,370 cases were included, of which 10.9% were coagulopathic. The COAST score performed with sensitivity 21.6% and specificity 94.2% at a threshold of COAST ≥ 3. The AUROC was 0.625 (95% CI 0.61-0.64). The COAST score also identified patients who had more massive transfusions (15.3% v 1.6%), more emergency surgery (49.6% v 28.2%), and higher early (21.7% v 5.4%) and total in-hospital mortality (38.1% v 14.5%). CONCLUSION: This large retrospective study demonstrated that the modified COAST score predicts coagulopathy with low sensitivity but high specificity. A positive COAST score identified a group of patients with bleeding-related adverse outcomes. This score appears adequate to act as an inclusion criterion for clinical trials targeting ATC.

Trauma-Induced Coagulopathy: Overview of an Emerging Medical Problem from Pathophysiology to Outcomes.

Coagulopathy induced by major trauma is common, affecting approximately one-third of patients after trauma. It develops independently of iatrogenic, hypothermic, and dilutive causes (such as iatrogenic cause in case of fluid administration), which instead have a pejorative aspect on coagulopathy. Notwithstanding the continuous research conducted over the past decade on Trauma-Induced Coagulopathy (TIC), it remains a life-threatening condition with a significant impact on trauma mortality. We reviewed the current evidence regarding TIC diagnosis and pathophysiological mechanisms and summarized the different iterations of optimal TIC management strategies among which product resuscitation, potential drug administrations, and hemostatis-focused approaches. We have identified areas of ongoing investigation and controversy in TIC management.

Characterization of organ dysfunction and mortality in pediatric patients with trauma with acute traumatic coagulopathy.

BACKGROUND: Traumatic injuries are a leading cause of mortality and morbidity in pediatric patients and abnormalities in hemostasis play an important role in these poor outcomes. One such abnormality, acute traumatic coagulopathy (ATC), is a near immediate endogenous response to injury and has recently been described in the pediatric population. This study aims to evaluate the epidemiology of pediatric ATC, specifically its association with organ dysfunction. METHODS: All patients with trauma presenting to the University of California, Benioff Children's Hospital Oakland between 2006 and 2015 with coagulation testing drawn at presentation were included. Patients were excluded if they (1) were >18 years of age, (2) were admitted with a non-mechanical mechanism of injury, (3) were on anticoagulation medications, or (4) had coagulation testing >4 hours after injury. ATC was defined as an international normalized ratio (INR) ≥1.3. The primary outcome was new or progressive multiple organ dysfunction syndrome (MODS) and secondary outcomes included in-hospital mortality and other morbidities. RESULTS: Of the 7382 patients that presented in the 10-year study period, 545 patients met criteria for analysis and 88 patients (16%) presented with ATC. Patients with ATC were more likely to develop MODS than those without ATC (68.4% vs 7.7%, p<0.001) and had higher in-hospital mortality (26.1% vs 0.4%, p<0.001) than those without ATC. Along with arterial hypotension and an Injury Severity Score ≥30, ATC was independent predictor of MODS and in-hospital mortality. An isolated elevated INR was associated with MODS and in-hospital mortality while an isolated elevated partial thromboplastin time was not. CONCLUSIONS: Pediatric ATC was associated with organ dysfunction, mortality, and other morbidities. ATC along with arterial hypotension and high injury severity were independent predictors of organ dysfunction and mortality. Pediatric ATC may be biologically distinct from adult ATC and further studies are needed. LEVEL OF EVIDENCE: IV, epidemiologic.