Background Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury. Methods Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick’s value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers. Results Patients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15–20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2. Conclusions This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.

Purpose Uncontrolled hemorrhage is still the major cause of preventable death after trauma and is aggravated by trauma-induced coagulopathy (TIC). The underlying pathophysiology of TIC is still elusive, but several key effectors such as the thrombin-generation capacity, the protein C (PC) pathway, and the fibrinolytic activity could be identified. The aim of this prospective observational study was to investigate plasma coagulation markers attributed to reflect the course of TIC and to identify the mechanisms being responsible for the coagulopathy after major trauma. Methods Seventy-three consecutive patients after major trauma and admission to a level-1-trauma unit were included to the study. During early trauma management, extended coagulation testing including the measurement of circulating thrombin markers and activated PC (APC) was performed and correlated with standard shock parameters and the patients’ clinical course and outcome. Results In contrast to standard coagulation parameters, thrombin markers and APC were found to be increased in correlation with injury severity. Even in patients with lower impact mechanisms, early endogenous accumulation of thrombin markers and APC (ISS < 16: 0.5 ng/ml; ISS ≥ 16–26: 1.5 ng/ml; ISS > 26: 4.1 ng/ml) were observed. Furthermore, APC showed ISS- and injury-dependent patterns while ROC curve analysis revealed that especially APC plasma levels were predictive for coagulopathy and general patient outcome. Conclusion Increased levels of APC and thrombin markers in patients after major trauma were positively correlated with injury severity. APC showed an ISS- and injury-dependent kinetic and might serve as candidate biomarker to identify patients at risk for developing TIC.