Background
The majority of potentially preventable deaths in trauma are due to uncontrolled hemorrhage and occur early after injury. How major bleeding is defined is integral to early identification ...and treatment of this group of high‐risk patients. However, there is no consensus on a definition of major bleeding in trauma. The aim of this Delphi study was to develop a consensus definition for research, with transfusion used as a surrogate marker of bleeding.
Study Design and Methods
Trauma experts from three international groups were invited to take part in an online Delphi survey. Over the course of four rounds, the group developed a number of definitions of major bleeding and reached consensus on a new definition.
Results
Forty‐four trauma experts agreed to become members of the Delphi panel, and 30 of 44 (68%) completed all four rounds. The panel agreed to exclude the historical massive transfusion definition (≥10 units of red blood cells within 24 hours). Consensus was reached on a new definition for use in clinical research: 4 or more units of any blood component within 2 hours of injury.
Conclusion
This Delphi process has yielded a pragmatic transfusion‐based definition of major bleeding. The consensus definition differs from historical definitions: a shorter time frame to reflect the acuity of bleeding, and multiple blood components in keeping with a balanced approach to resuscitation. The definition developed may be best suited to mature trauma systems (reflecting the demographics of the expert panel), and could be used to guide registry data recording and to characterize patients at risk of major bleeding.
Viscoelastic hemostatic assays such as rotational thromboelastometry (ROTEM®) are used to guide treatment of trauma induced coagulopathy. We hypothesized that ROTEM derangements reflect specific ...coagulation factor deficiencies after trauma.
Secondary analysis of a prospective cohort study in six European trauma centers in patients presenting with full trauma team activation. Patients with dilutional coagulopathy and patients on anticoagulants were excluded. Blood was drawn on arrival for measurement of ROTEM®, coagulation factor levels and markers of fibrinolysis. ROTEM® cut-off values to define hypocoagulability were: EXTEM clotting time (CT) >80s, EXTEM clot amplitude after 5 minutes (CA5) <40mm, EXTEM lysis at 30 minutes (Li30) <85%, FIBTEM clot amplitude after 5 minutes (CA5) <10mm and FIBTEM lysis at 30 minutes (Li30) <85%. Based on these, patients were divided into 7 deranged ROTEM® profiles and compared to the reference group (ROTEM® values within reference range). The primary endpoint was coagulation factors levels and fibrinolysis.
Of 1828 patients, 40% had ROTEM® derangements 40.0%, most often consisting of a combined decrease in EXTEM and FIBTEM CA5, that was present in 217 (11.9%) patients. While an isolated EXTEM CT>80s had no impact on mortality, all other ROTEM® derangements were associated with increased mortality. Also, coagulation factor levels in this group were similar to patients with a normal ROTEM®. Of coagulation factors, decrease was most apparent for fibrinogen (with a nadir of 0.78 g/L) and for factor V levels (with a nadir of 22.8%). In addition, increased fibrinolysis can be present when LI30 is normal but EXTEM and FIBTEM CA5 is decreased.
Coagulation factor levels and mortality in the group with an isolated clotting time prolongation is similar to patients with a normal ROTEM ®. Other ROTEM ® derangements are associated with mortality and reflect a depletion of fibrinogen and factor V. Increased fibrinolysis can be present when lysis after 30 minutes is normal.
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,
= 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.
What's new for trauma haemorrhage management? Vulliamy, Paul; Thaventhiran, Anthony J; Davenport, Ross A
British journal of hospital medicine,
05/2019, Letnik:
80, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Uncontrolled haemorrhage is the leading cause of preventable death from injury and is a major contributor to the global burden of disease. The majority of deaths resulting from bleeding occur within ...the first 3 hours of hospital admission, and the window for meaningful intervention is therefore extremely small. Resuscitative efforts during active bleeding should focus on maintaining haemostatic function with blood product transfusion and early administration of tranexamic acid. Achieving control of haemorrhage is the overarching treatment priority and may require temporising measures before definitive surgical or radiological intervention. This review summarizes the contemporary approaches to resuscitation of bleeding trauma patients, options for achieving haemorrhage control, and current areas of active research including organ protective resuscitation and suspended animation.
Trauma-induced coagulopathy results from a complex interplay between shock resuscitation and impaired clotting protease function. A pathophysiological role of platelets in this condition remains as ...yet undefined. This review examines our current knowledge of platelet function in haemostasis, possible mechanisms for aberrant activity in trauma and the role of platelet transfusions in exsanguinating haemorrhage.
Platelet adhesion and aggregation enable a haemostatic plug to form at the site of vessel injury. As described within cell-based models of thrombin generation, platelet membranes provide a platform to amplify clot formation. There is evidence to suggest platelet activity may be of greater importance than platelet number for clot integrity. Analysis of platelet function is limited by currently available devices. Therefore, the precise role and triggers for platelet transfusion in trauma have yet to be fully characterized. Retrospective studies show that early high-volume platelet transfusion in trauma may be associated with similar outcome benefits observed in high ratio plasma: red blood cell replacement.
Platelets undoubtedly play a pivotal role in haemostasis and trauma-induced coagulopathy. However, their specific dysfunction in trauma remains to be elucidated. Further research to characterize the dysfunctional pathways of the platelet response is required, together with clinical trials of the optimal timing and dose of platelet transfusions.
The massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and ...lack supporting clinical evidence. Damage-control resuscitation regimens of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive transfusion requirements could allow early activation of blood bank protocols.
Datasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability of death. A logistic regression model for the prediction of massive transfusion, defined as 10 or more units of red cell transfusions, was developed.
In total, 5,693 patient records were available for analysis. Mortality increased as transfusion requirements increased, but the model indicated no threshold effect. Mortality was 9% in patients who received none to five PRBC units, 22% in patients receiving six to nine PRBC units, and 42% in patients receiving 10 or more units. A logistic model for prediction of massive transfusion was developed and validated at multiple sites but achieved only moderate performance. The area under the receiver operating characteristic curve was 0.81, with specificity of only 50% at a sensitivity of 90% for the prediction of 10 or more PRBC units. Performance varied widely at different trauma centers, with specificity varying from 48% to 91%.
No threshold for definition exists at which a massive transfusion specifically results in worse outcomes. Even with a large sample size across multiple trauma datasets, it was not possible to develop a transportable and clinically useful prediction model based on available admission parameters. Massive transfusion as a concept in trauma has limited utility, and emphasis should be placed on identifying patients with massive hemorrhage and acute traumatic coagulopathy.
Abstract Uncontrolled bleeding is the most common preventable cause of death for patients with severe injury. Coagulopathy inevitably accompanies severe bleeding, exacerbated by the ongoing blood ...loss and the treatments administered. There is debate about the underlying pathophysiological mechanisms of early traumatic coagulopathy and uncertainty about whether injury induces a unique coagulopathy when compared to other forms of major haemorrhage. This review describes current understanding of the coagulopathy of major blood loss and focuses on the early coagulation changes that occur following severe injury. It then reports on the contemporary management of coagulopathic bleeding using new transfusion strategies. Finally this review presents some practical points to the delivery of transfusion for major blood loss in the modern hospital setting.
The importance of dysregulation of microRNA (miRNA) expression in nonalcoholic steatohepatitis (NASH) has been increasingly recognized; however, the association between altered expression of miRNAs ...and pathophysiological features of NASH and whether there is a connection between susceptibility to NASH and altered expression of miRNAs are largely unknown. In this study, male inbred C57BL/6J and DBA/2J mice were fed a lipogenic methyl-deficient diet that causes liver injury similar to human NASH, and the expression of miRNAs and the level of proteins targeted by these miRNAs in the livers were determined. Administration of the methyl-deficient diet triggered NASH-specific changes in the livers of C57BL/6J and DBA/2J mice, with the magnitude being more severe in DBA/2J mice. This was evidenced by a greater extent of expression of fibrosis-related genes in the livers of methyl-deficient DBA/2J mice. The development of NASH was accompanied by prominent changes in the expression of miRNAs, including miR-29c, miR-34a, miR-155, and miR-200b. Interestingly, changes in the expression of these miRNAs and protein levels of their targets, including Cebp-β, Socs 1, Zeb-1, and E-cadherin, in the livers of DBA/2J mice fed a methyl-deficient diet were more pronounced as compared with those in C57BL/6J mice. These results show that alterations in the expression of miRNAs are a prominent event during development of NASH induced by methyl deficiency and strongly suggest that severity of NASH and susceptibility to NASH may be determined by variations in miRNA expression response. More important, our data provide a mechanistic link between alterations in miRNA expression and pathophysiological and pathomorphological features of NASH.
Airborne LiDAR (Light Detection and Ranging) is a remote sensing technology that offers the ability to collect high horizontal sampling densities of high vertical resolution vegetation height data, ...over larger spatial extents than could be obtained by field survey. The influence of vegetation structure on the bird is a key mechanism underlying bird–habitat models. However, manual survey of vegetation structure becomes prohibitive in terms of time and cost if sampling needs to be of sufficient density to incorporate fine‐grained heterogeneity at a landscape extent. We show that LiDAR data can help bridge the gap between grain and extent in organism–habitat models. Two examples are provided of bird–habitat models that use structural habitat information derived from airborne LiDAR data. First, it is shown that data on crop and field boundary height can be derived from LiDAR data, and so have the potential to predict the distribution of breeding Sky Larks in a farmed landscape. Secondly, LiDAR‐retrieved canopy height and structural data are used to predict the breeding success of Great Tits and Blue Tits in broad‐leaved woodland. LiDAR thus offers great potential for parameterizing predictive bird–habitat association models. This could be enhanced by the combination of LiDAR data with multispectral remote sensing data, which enables a wider range of habitat information to be derived, including both structural and compositional characteristics.
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