Tranexamic acid stops hyperfibrinolysis in dogs with hemorrhagic shock: a randomized, controlled clinical trial.

OBJECTIVE: To determine the effect of tranexamic acid (TXA) on clot hyperfibrinolysis (HF), defined as excessive clot lysis at 30 minutes (LY30%), with rapid thromboelastography (rTEG) or rTEG samples spiked with tissue plasminogen activator (tPA-stressed rTEG), in dogs with hemorrhagic shock. METHODS: Prospective blinded clinical trial at 2 teaching hospitals, March 16, 2018, to May 20, 2022. Twenty-five dogs with hemorrhagic shock and HF were treated with standard care plus either TXA (20 mg/kg; TXA group) or saline (SAL group) over 20 minutes followed by an infusion of the same dose over 8 hours. Rapid TEG and tPA-stressed rTEG assays were performed immediately before study drug administration and at 8, 12, and 24 hours afterwards (T0, T8, T12, and T24, respectively). RESULTS: 4 dogs died or were euthanized before the end of the study period due to disease/injury severity. All survivors had normal rTEG LY30% values after T0; the value for 1 nonsurvivor increased at T8. The tPA-stressed LY30% normalized in all TXA (n = 14) and 8 of 11 SAL dogs at T8; TXA dogs had lower median tPA-stressed rTEG LY30% values at T8 and T12 than SAL dogs (P = .001 and .02, respectively). There was no treatment effect on blood product administration or survival, and no adverse effects were attributed to TXA administration. CONCLUSIONS: Resuscitation with or without TXA reduced HF identified by tPA-stressed rTEG. Hyperfibrinolysis was completely suppressed at the conclusion of the 8-hour TXA infusion. CLINICAL RELEVANCE: Although TXA treatment stopped HF, there was no effect on survival or transfusion requirements.

Ghrelin may protect against vascular endothelial injury in Acute traumatic coagulopathy by mediating the RhoA/ROCK/MLC2 pathway.

Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment.

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.

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.

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.

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.

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.

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.

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.

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.

A Machine Learning-Based Model to Predict Acute Traumatic Coagulopathy in Trauma Patients Upon Emergency Hospitalization.

Acute traumatic coagulopathy (ATC) is an extremely common but silent murderer; this condition presents early after trauma and impacts approximately 30% of severely injured patients who are admitted to emergency departments (EDs). Given that conventional coagulation indicators usually require more than 1 hour after admission to yield results-a limitation that frequently prevents the ability for clinicians to make appropriate interventions during the optimal therapeutic window-it is clearly of vital importance to develop prediction models that can rapidly identify ATC; such models would also facilitate ancillary resource management and clinical decision support. Using the critical care Emergency Rescue Database and further collected data in ED, a total of 1385 patients were analyzed and cases with initial international normalized ratio (INR) values >1.5 upon admission to the ED met the defined diagnostic criteria for ATC; nontraumatic conditions with potentially disordered coagulation systems were excluded. A total of 818 individuals were collected from Emergency Rescue Database as derivation cohorts, then were split 7:3 into training and test data sets. A Pearson correlation matrix was used to initially identify likely key clinical features associated with ATC, and analysis of data distributions was undertaken prior to the selection of suitable modeling tools. Both machine learning (random forest) and traditional logistic regression were deployed for prediction modeling of ATC. After the model was built, another 587 patients were further collected in ED as validation cohorts. The ATC prediction models incorporated red blood cell count, Shock Index, base excess, lactate, diastolic blood pressure, and potential of hydrogen. Of 818 trauma patients filtered from the database, 747 (91.3%) patients did not present ATC (INR ≤ 1.5) and 71 (8.7%) patients had ATC (INR > 1.5) upon admission to the ED. Compared to the logistic regression model, the model based on the random forest algorithm showed better accuracy (94.0%, 95% confidence interval [CI]: 0.922-0.954 to 93.5%, 95% CI: 0.916-0.95), precision (93.3%, 95% CI: 0.914-0.948 to 93.1%, 95% CI: 0.912-0.946), F1 score (93.4%, 95% CI: 0.915-0.949 to 92%, 95% CI: 0.9-0.937), and recall score (94.0%, 95% CI: 0.922-0.954 to 93.5%, 95% CI: 0.916-0.95) but yielded lower area under the receiver operating characteristic curve (AU-ROC) (0.810, 95% CI: 0.673-0.918 to 0.849, 95% CI: 0.732-0.944) for predicting ATC in the trauma patients. The result is similar in the validation cohort. The values for classification accuracy, precision, F1 score, and recall score of random forest model were 0.916, 0.907, 0.901, and 0.917, while the AU-ROC was 0.830. The values for classification accuracy, precision, F1 score, and recall score of logistic regression model were 0.905, 0.887, 0.883, and 0.905, while the AU-ROC was 0.858. We developed and validated a prediction model based on objective and rapidly accessible clinical data that very confidently identify trauma patients at risk for ATC upon their arrival to the ED. Beyond highlighting the value of ED initial laboratory tests and vital signs when used in combination with data analysis and modeling, our study illustrates a practical method that should greatly facilitates both warning and guided target intervention for ATC.

Early changes of coagulation function in a swine traumatic model within 1 hour after traumatic hemorrhagic shock induced by Gunshot injury / 解放军医学杂志

Objective To explore the potential mechanism of traumatic coagulopathy through investigating the periodic change of hemodynamics, acid-base system, and coagulation system within 1 hour after traumatic hemorrhagic shock. Methods Adult healthy Landrace pigs were anesthetized to establish a model of hemorrhagic shock-induced by gunshot wounds. Vital signs, Hemodynamic parameters were monitored, and arterial blood gas, routine coagulation as well as thromboelastogram were tested at 15 minutes before the injury, shock point, 10 minutes after the shock, 30 minutes after the shock, and 1 hour after the shock, respectively. Results Among the 16 Landrace pigs that were examined, the mean total blood loss was (1444.22±205.50) ml with a 1-hour survival rate of 68.75%. Among the 11 pigs which survived over 1 hour, Hemodynamic and arterial blood gas analysis showed characteristics of stages. Analysis coagulation test showed that R value, PT and APTT are periodically decreased. The MA value decreased significantly from injury to 10 minutes after shock point (P<0.05), and LY30 showed a significant decreased from 10 minutes aftershock to 1-hour aftershock (P=0.038). In the correlation analysis of coagulation changes, there was a correlation between APTT value and heart rate, diastolic blood pressure, systolic blood pressure, MAP (P<0.05); R value was related to heart rate, SVI, systolic blood pressure, and MAP (P<0.05); MA value was related to BE, LAC, K+, PH, Ca2+, and SVI (P<0.05). Conclusion Within 1 hour after severe traumatic hemorrhagic shock, the coagulation system is in a hypercoagulable state. At 10 minutes after the shock, the fibrinolytic system is inhibited and the fibrinolysis is shut down, which may further aggravate the hypercoagulable state.

Tools to predict acute traumatic coagulopathy in the pre-hospital setting: a review of the literature.

INTRODUCTION: Recognising acute traumatic coagulopathy (ATC) poses a significant challenge to improving survival in emergency care. Paramedics are in a prime position to identify ATC in pre-hospital major trauma and initiate appropriate coagulopathy management. METHOD: A database literature review was conducted using Scopus, CINAHL and MEDLINE. RESULTS: Two themes were identified from four studies: prediction tools, and point-of-care testing. Prediction tools identified key common ATC markers in the pre-hospital setting, including: systolic blood pressure, reduced Glasgow Coma Score and trauma to the chest, abdomen and pelvis. Point-of-care testing was found to have limited value. CONCLUSION: Future research needs to explore paramedics using prediction tools in identifying ATC, which could alert hospitals to prepare for blood products for damage control resuscitation.

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.

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self-propelling particles.

BACKGROUND: Endogenous fibrinolytic activation contributes to coagulopathy and mortality after trauma. Administering tranexamic acid (TXA), an antifibrinolytic agent, is one strategy to reduce bleeding; however, it must be given soon after injury to be effective and minimize adverse effects. Administering TXA topically to a wound site would decrease the time to treatment and could enable both local and systemic delivery if a suitable formulation existed to deliver the drug deep into wounds adequately. OBJECTIVES: To determine whether self-propelling particles could increase the efficacy of TXA. METHODS: Using previously developed self-propelling particles, which consist of calcium carbonate and generate CO2 gas, TXA was formulated to disperse in blood and wounds. The antifibrinolytic properties were assessed in vitro and in a murine tail bleeding assay. Self-propelled TXA was also tested in a swine model of junctional hemorrhage consisting of femoral arteriotomy without compression. RESULTS: Self-propelled TXA was more effective than non-propelled formulations in stabilizing clots from lysis in vitro and reducing blood loss in mice. It was well tolerated when administered subcutaneously in mice up to 300 to 1000 mg/kg. When it was incorporated in gauze, four of six pigs treated after a femoral arteriotomy and without compression survived, and systemic concentrations of TXA reached approximately 6 mg/L within the first hour. CONCLUSIONS: A formulation of TXA that disperses the drug in blood and wounds was effective in several models. It may have several advantages, including supporting local clot stabilization, reducing blood loss from wounds, and providing systemic delivery of TXA. This approach could both improve and simplify prehospital trauma care for penetrating injury.

Efficiency of a pelvic circumferential compression device for continuous hemorrhage of peripheral soft tissue of the pelvis: A case report.

BACKGROUND: A pelvic circumferential compression device (PCCD) is a belt that is wrapped around a fractured pelvis and tightened with a closing mechanism. The SAM Sling® is one of the most common PCCDs used for trauma management. Although the use of the SAM Sling® for reduction and stabilization of unstable pelvic ring fracture has become the standard of care in most relevant trauma scenarios, it is not usually used for stopping continuous hemorrhage of the peripheral soft tissue of the pelvis without unstable pelvic ring fractures. CASE PRESENTATION: We report the case of a 79-year-old woman with life-threatening and unexpected continuous subcutaneous and intramuscular hemorrhage of the buttocks and groin area. She did not have unstable pelvic ring fractures but had hemorrhagic shock and acute traumatic coagulopathy (ATC). By use of the SAM Sling®, the hemorrhage was controlled, and she was eventually rescued. CONCLUSIONS: We propose the use of the SAM Sling® to stop continuous bleeding in the state of ATC regardless of unstable pelvic ring fracture.

Viscoelastic Monitoring to Guide the Correction of Perioperative Coagulopathy and Massive Transfusion in Patients with Life-Threatening Hemorrhage.

The resuscitation of patients with traumatic hemorrhage remains a challenging clinical scenario. The appropriate and aggressive support of the patient's coagulation is of critical importance. Conventional coagulation assays present several shortcomings in this setting. The integration of viscoelastic monitoring in clinical practice has the potential to result in significant improvements. In order to be successful, the provider must understand basics of the methodology, read outs, and the limitations of the technique.

Characteristics of hyperfibrinolysis in dogs and cats demonstrated by rotational thromboelastometry (ROTEM).

Hyperfibrinolysis (HFL) is a pathophysiological mechanism that has not been described in dogs or cats extensively. The aim of this study was to describe rotational thromboelastometry (ROTEM) parameters and underlying diagnosis in dogs and cats with HFL and evaluate association with bleeding diathesis. The ROTEM database was retrospectively searched for EXTEM (ROTEM activated with proprietary tissue factor) tracings with maximum lysis at 60min ≥15%. Concurrent ROTEM and plasma coagulation tests, thrombocyte number, diagnosis and survival to hospital discharge were extracted from medical records. Analysis of differences between dogs and cats and of factors associated with bleeding, fulminant HFL (clot breakdown within 30min) and survival to hospital discharge were performed. Hyperfibrinolysis was detected in eight cats presenting with haemoabdomen or haemothorax (n=4/8, 50%) and trauma (n=3/8, 38%) and in 36 dogs with angiostrongylosis (n=12, 33%), neoplasia (n=7, 19%), liver disease (n=4, 11%) and others including apparently healthy dogs (n=3, 8%). Hyperfibrinolysis was associated with prolonged EXTEM and APTEM (EXTEM with added apoprotein for inhibition of HFL) clotting time and decreased FIBTEM (EXTEM with added cytochalasin D for inhibition of thrombocytes) maximum clot firmness (MCF) in dogs and cats and with decreased EXTEM MCF in dogs. Bleeding dogs had significantly hypocoagulable EXTEM tracings. Fulminant HFL was associated with severe hypofibrinogenaemia in dogs (P=0.005) and was not associated with survival to hospital discharge. Evidence of HFL was demonstrated in dogs and cats with bleeding, trauma, parasitic and neoplastic disease. HFL is associated with late and weak clot formation.

Rotation thromboelastometry (ROTEM) enables improved outcomes in the pediatric trauma population.

OBJECTIVE: We evaluated the role of rotation thromboelastometry (ROTEM) in managing acute traumatic coagulopathy in pediatric patients with trauma. METHODS: A retrospective cohort of pediatric patients with trauma from six institutes was studied during a 10-year period from 2007 to 2017. The associations between ROTEM-guided, goal-directed coagulation therapy and clinical outcomes were determined. RESULTS: Three hundred thirty-two pediatric patients (age < 15 years) who were treated with ROTEM-guided, goal-directed coagulation therapy were matched to 332 control pediatric patients with conventional plasmatic coagulation tests. The ROTEM protocol was associated with a significant reduction in the interval for admission to acute traumatic coagulopathy treatment, less plasma transfusions in the first 24 hours of admission, and a favorable coagulopathy recovery. Furthermore, the median number of total hospital days was significantly shorter for patients who had the ROTEM protocol than for control patients. CONCLUSIONS: There are significant favorable outcomes, including rapid acute traumatic coagulopathy treatment and a lower 24-hour blood product requirement, following ROTEM-guided, goal-directed coagulation therapy among pediatric patients with blunt trauma.