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.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.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.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. 

/pdf/the-european-guideline-on-management-of-major-bleeding-and-12utukle.pdf

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

Pathophysiology of Trauma-Induced Coagulopathy

Background: Haemorrhage is a major cause of death in severe trauma. Fibrinogen plays a critical role in maintaining haemostasis in traumatic haemorrhage, and early replacement using fibrinogen concentrate (FC) or cryoprecipitate (Cryo) is recommended by several international trauma guidelines. Limited evidence supports one product over the other, with widespread geographic and institutional variation in practice. Two previous trials have investigated the feasibility of rapid FC administration in severely injured trauma patients, with conflicting results.Objective: To compare the time to fibrinogen replacement using FC or Cryo in severely injured trauma patients with major haemorrhage and hypofibrinogenaemia.Design, setting, patients and interventions: A multicentre controlled pilot trial in which adult trauma patients with haemorrhage were randomly assigned (1:1) to receive FC or Cryo for fibrinogen replacement, guided by FIBTEM A5 (functional fibrinogen assessment at 5 minutes after clot formation, using rotational thromboelastometry).Main outcome measures: The primary outcome was time to commencement of fibrinogen replacement. Secondary outcomes included effects of the intervention on plasma fibrinogen levels and clinical outcomes including transfusion requirements and mortality.Results: Of the 100 randomly assigned patients, 62 were hypofibrinogenaemic and received the intervention (n = 37) or Cryo (n = 25). Median (interquartile range [IQR]) time to delivery of FC was 29 min (23-40 min) compared with 60 min (4080 min) for Cryo (P = 0.0001). All 62 patients were hypofibrinogenaemic before receiving FC or Cryo (FC: median FIBTEM A5, 8 mm [ IQR, 7-9 mm]; Cryo: median FIBTEM A5, 9 mm [IQR, 5-10 mm]). In the FC arm patients received a median of 3 g FC (IQR, 2-4 g), and in the Cryo arm patients received a median of 8 units of Cryo (IQR, 8-14 units). Restoration of fibrinogen levels was achieved in both arms after the intervention. Blood product transfusion, fluid resuscitation and thromboembolic complications were similar in both arms. Overall mortality was 15.3%, with more deaths in the FC arm.Conclusion: Fibrinogen replacement in severely injured trauma patients with major haemorrhage and hypofibrinogenaemia was achieved substantially faster using FC compared with Cryo. Fibrinogen levels increased appropriately using either product. The optimal method for replacing fibrinogen in traumatic haemorrhage is controversial. Our results will inform the design of a larger trial powered to assess patient-centred outcomes.

/pdf/fibrinogen-early-in-severe-trauma-study-feisty-results-from-57pfyelo67.pdf

Fibrinogen Early In Severe Trauma studY (FEISTY): results from an Australian multicentre randomised controlled pilot trial

Tissue engineering has a great application prospect as an effective treatment for tissue and organ injury, functional reduction, or loss. Bioactive tissues are reconstructed and damaged organs are repaired by the three elements, including cells, scaffold materials, and growth factors. Graphene-based composites can be used as reinforcing auxiliary materials for tissue scaffold preparation because of their large specific surface area, and good mechanical support. Tissue engineering scaffolds with graphene-based composites have been widely studied. Part of research have focused on the application of graphene-based composites in single tissue engineering. The basic principles of graphene materials used in tissue engineering are summarized in some research. Some studies emphasized the key problems and solutions urgently needed to be solved in the development of tissue engineering and discussed their application prospect. Some related studies mainly focused on the conductivity of graphene and discussed the application of electroactive scaffolds in tissue engineering. In this review, the composite materials for preparing tissue engineering scaffolds are briefly described, which emphasizes the preparation methods, biological properties, and practical applications of graphene-based composite scaffolds. The synthetic techniques, with stressing solvent casting, electrospinning, and three-dimensional printing, are introduced in detail. The mechanical, cell-oriented, and biocompatible properties of graphene-based composite scaffolds in tissue engineering are analyzed and summarized. Their applications in bone tissue engineering, nerve tissue engineering, cardiovascular tissue engineering, and other tissue engineering are summarized systematically. In addition, this work also looks forward to the difficulties and challenges in the future research, providing some references for the follow-up research of graphene-based composites in tissue engineering scaffolds. Impact statement Regeneration and repair of tissue and organ injury has become a new research hotspot in recent years. Tissue engineering scaffolds prepared with graphene-based materials have good biocompatibility, excellent mechanical properties, and strong cell orientation, which can fully induce the proliferation and differentiation of seed cells. This review briefly describes the basic materials for the preparation of tissue engineering scaffolds, and focuses on the preparation, performance, and application of graphene-based materials in tissue engineering, providing sufficient understanding of graphene applied in regenerative medicine. 

Preparation, Properties, and Application of Graphene-Based Materials in Tissue Engineering Scaffolds

Trauma is a leading cause of mortality, with major bleeding and trauma-induced coagulopathy (TIC) contributing to negative patient outcomes. Treatments for TIC include tranexamic acid (TXA), fresh frozen plasma (FFP), and coagulation factor concentrates (CFCs, e.g. prothrombin complex concentrates [PCCs] and fibrinogen concentrate [FCH]). Guidelines for TIC management vary across Europe and a clear definition of TIC is still lacking. An advisory board involving European trauma experts was held on 02 February 2019, to discuss clinical experience in the management of trauma-related bleeding and recommendations from European guidelines, focusing on CFC use (mainly FCH). This review summarises the discussions, including TIC definitions, gaps in the guidelines that affect their implementation, and barriers to use of CFCs, with suggested solutions. A definition of TIC, which incorporates clinical (e.g. severe bleeding) and laboratory parameters (e.g. low fibrinogen) is suggested. TIC should be treated immediately with TXA and FCH/red blood cells; subsequently, if fibrinogen ≤ 1.5 g/L (or equivalent by viscoelastic testing), treatment with FCH, then PCC (if bleeding continues) is suggested. Fibrinogen concentrate, and not FFP, should be administered as first-line therapy for TIC. Several initiatives may improve TIC management, with improved medical education of major importance; generation of new and stronger data, simplified clinical practice guidance, and improved access to viscoelastic testing are also critical factors. Management of TIC is challenging. A standard definition of TIC, together with initiatives to facilitate effective CFC administration, may contribute to improved patient care and outcomes.

/pdf/variations-and-obstacles-in-the-use-of-coagulation-factor-1i9lud9awb.pdf

Variations and obstacles in the use of coagulation factor concentrates for major trauma bleeding across Europe: outcomes from a European expert meeting

Hypercoagulability can occur after severe tissue injury, that is likely related to tissue factor exposure and impaired endothelial release of tissue plasminogen activator (tPA). In contrast, when shock and hypoperfusion occur, activation of the protein C pathway and endothelial tPA release induce a shift from a procoagulant to a hypocoagulable and hyperfibrinolytic state with a high risk of bleeding. Both thrombotic and bleeding phenotypes are associated with increased mortality and are influenced by the extent and severity of tissue injury and degree of hemorrhagic shock. Response to trauma is a complex, dynamic process in which risk can shift from bleeding to thrombosis depending on the injury pattern, hemostatic treatment, individual responses, genetic predisposition, and comorbidities. Based on this body of knowledge, we will review and consider future directions for the management of severely injured trauma patients.

Pathophysiological Response to Trauma-Induced Coagulopathy: A Comprehensive Review.

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Pathophysiology of Trauma-Induced Coagulopathy

Pathophysiological Response to Trauma-Induced Coagulopathy: A Comprehensive Review.