IntroductionHigh mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.MethodsOne hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.ResultsPlasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.ConclusionsThe results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.

IntroductionThe purpose of this study was to re-evaluate the findings of a smaller cohort study on the functional definition and characteristics of acute traumatic coagulopathy (ATC). We also aimed to identify the threshold values for the most accurate identification of ATC and prediction of massive transfusion (MT) using rotational thromboelastometry (ROTEM) assays.MethodsIn this prospective international multicentre cohort study, adult trauma patients who met the local criteria for full trauma team activation from four major trauma centres were included. Blood was collected on arrival to the emergency department and analyzed with laboratory international normalized ratio (INR), fibrinogen concentration and two ROTEM assays (EXTEM and FIBTEM). ATC was defined as laboratory INR >1.2. Transfusion requirements of ≥10 units of packed red blood cells within 24 hours were defined as MT. Performance of the tests were evaluated by receiver operating characteristic curves, and calculation of area under the curve (AUC). Optimal cutoff points were estimated based on Youden index.ResultsIn total, 808 patients were included in the study. Among the ROTEM parameters, the largest AUCs were found for the clot amplitude (CA) 5 value in both the EXTEM and FIBTEM assays. EXTEM CA5 threshold value of ≤37 mm had a detection rate of 66.3% for ATC. An EXTEM CA5 threshold value of ≤40 mm predicted MT in 72.7%. FIBTEM CA5 threshold value of ≤8 mm detected ATC in 67.5%, and a FIBTEM CA5 threshold value ≤9 mm predicted MT in 77.5%. Fibrinogen concentration ≤1.6 g/L detected ATC in 73.6% and a fibrinogen concentration ≤1.90 g/L predicted MT in 77.8%. Patients with either an EXTEM or FIBTEM CA5 below the optimum detection threshold for ATC received significantly more packed red blood cells and plasma.ConclusionsThis study confirms previous findings of ROTEM CA5 as a valid marker for ATC and predictor for MT. With optimum threshold for EXTEM CA5 ≤ 40 mm and FIBTEM CA5 ≤ 9 mm, sensitivity is 72.7% and 77.5% respectively. Future investigations should evaluate the role of repeated viscoelastic testing in guiding haemostatic resuscitation in trauma.

Trauma remains the leading cause of morbidity and mortality in the United States among children from the age 1 year to 21 years old. The most common cause of lethality in pediatric trauma is traumatic brain injury (TBI). Early coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumatic brain injury. In contrast to adult patients, massive bleeding is less common after pediatric trauma. The classical drivers of trauma-induced coagulopathy (TIC) include hypothermia, acidosis, hemodilution and consumption of coagulation factors secondary to local activation of the coagulation system following severe traumatic injury. Furthermore, there is also recent evidence for a distinct mechanism of TIC that involves the activation of the anticoagulant protein C pathway. Whether this new mechanism of posttraumatic coagulopathy plays a role in children is still unknown. The goal of this review is to summarize the current knowledge on the incidence and potential mechanisms of coagulopathy after pediatric trauma and the role of rapid diagnostic tests for early identification of coagulopathy. Finally, we discuss different options for treating coagulopathy after severe pediatric trauma.