Acute coagulopathy of trauma: Balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation
Introduction
Acute coagulopathy secondary to trauma predicts a poor clinical outcome. Currently there are two models aiming at its explanation. Brohi et al. introduced the concept Acute Coagulopathy of Trauma Shock (ACoTS), emphasizing the contribution of enhanced activation of the protein C pathway and hyperfibrinolysis to the observed hypocoagulability, with the main drivers of the coagulopathy being tissue trauma, shock and ensuing hypoperfusion [1]. Conversely, other consider the acute coagulopathy of trauma as disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, with the main cause of increased bleeding tendency being consumption of coagulation factors and platelets secondary to the tissue trauma [2], [3]. Common for both models, however, is that only the fluid phase of the hemostatic system or, more correctly, only the concentration of different elements in the plasma fraction of the fluid phase, has previously been investigated.
The hypothesis delineated in the present paper infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. Furthermore, we infer that evaluating the functionality of the fluid phase, i.e., whole blood, is critical for a thorough understanding of coagulopathy secondary to trauma.
Section snippets
Injury severity and acute coagulopathy of trauma evaluated in whole blood
The literature reports a dose-dependency with regards to injury severity and the hemostatic response to trauma. When employing whole blood viscoelastical assays like thrombelastography (TEG), different hemostatic profiles of the fluid phase appear related to the severity of tissue injury (Fig. 1) [4]. As opposed to conventional plasma based coagulation assays (prothrombin time (PT), activated partial thromboplastin time (APTT)), TEG specifically identifies both hypercoagulability and
Catecholamines and trauma
We hypothesize that a major driver of the “coagulopathy” of trauma is the neurohumoral response, specifically the dose-dependent sympathoadrenal activation secondary to the trauma, inferring that the released circulating catecholamines influence the endothelium with an overall aim to induce local hemostasis while preserving perfusion and oxygen delivery. Consequently, the hemostatic changes observed in the fluid phase are determined by the effect of the catecholamines on the endothelium. We
Pro- and anticoagulant gradients in the hemostatic system
As outlined above, an important regulator of the pro- and anticoagulant states of the fluid (blood) and solid (endothelium) phases, respectively, are the spatial effects inflicted by the trauma and the sympathoadrenal response on the endothelium. With an intact endothelium, the anticoagulant properties are located at the endothelial surface (glycocalyx, TM-PC system, prostacyclin and NO) and thereby up-concentrated in the cell suspension near the vascular endothelium (platelets) rather than
Testing the hypothesis
To provide evidence for a critical role of catecholamine induced endothelial activation and damage to the progressively evolving hypo- and anticoagulation of the fluid phase secondary to severe trauma, a relation between injury severity, plasma catecholamines and the hemostatic response in the circulating blood and at the endothelium needs to be established. Also, the magnitude of the injury and the associated sympathoadrenal response should be able to predict development of acute traumatic
Clinical implications
Death due to trauma is the leading cause of lost life years worldwide, with hemorrhage being responsible for 40% of all trauma deaths [5]. Given the complex interactions between multiple neurohumoral systems in trauma, and the devastating outcome of uncontrolled, exaggerated and imbalanced actions of these systems, improved understanding may reveal pathophysiologic mechanisms with potentially new therapeutic targets. Finally, it should be emphasized that though the present paper focuses on the
Conflicts of interest
The authors declare no conflict of interests.
Acknowledgements
The authors received no funding and were not sponsored while writing the manuscript.
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