Experimental Models of Traumatic Injuries: Do They Capture the Coagulopathy and Underlying Endotheliopathy Induced by Human Trauma?

Abstract

Trauma-induced coagulopathy (TIC) is a major cause of morbidity and mortality in patients with traumatic injury. It describes the spectrum of coagulation abnormalities that occur because of the trauma itself and the body’s response to the trauma. These coagulation abnormalities range from hypocoagulability and hyperfibrinolysis, resulting in potentially fatal bleeding, in the early stages of trauma to hypercoagulability, leading to widespread clot formation, in the later stages. Pathological changes in the vascular endothelium and its regulation of haemostasis, a phenomenon known as the endotheliopathy of trauma (EoT), are thought to underlie TIC. Our understanding of EoT and its contribution to TIC remains in its infancy largely due to the scarcity of experimental research. This review discusses the mechanisms employed by the vascular endothelium to regulate haemostasis and their dysregulation following traumatic injury before providing an overview of the available experimental in vitro and in vivo models of trauma and their applicability for the study of the EoT and its contribution to TIC.

Shear Stress and Endothelial Mechanotransduction in Trauma Patients with Hemorrhagic Shock: Hidden Coagulopathy Pathways and Novel Therapeutic Strategies

“…Increases in glycocalyx shedding and vascular permeability correlate with larger reductions in blood flow, as demonstrated in the postcapillary venules of skeletal muscle and mesentery of rats [43,54,124]. Furthermore, loss of the endothelial barrier leads to the exposure of procoagulant and plateletactivating proteins, the shedding of glycocalyx components, hypocoagulability, and the release of fibrinolytic factors promoting fibrin(ogen)olysis [8,66,121,125].…”

“…After traumatic injury, coagulation, anti-coagulation, and fibrinolysis are disproportionally affected in a dynamic manner, leading to impaired hemostasis. Of note is that trauma is a heterogeneous event, and it is difficult to define a dominant mechanism of TIC [6,8,9]. The latter has been considered to be primarily due to blood loss from injury, hemodilution from aggressive resuscitation, and the development of hypothermia and acidosis [10,11].…”