IMPORTANCE Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI.OBJECTIVE To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. INTERVENTIONS Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). MAIN OUTCOMES AND MEASURESThe primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. RESULTS Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month followup. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, −0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, −2.9% [95% CI, −7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, −0.9 [95% CI, −2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, −5.4% [95% CI, −12.8% to 2.1%]; P = .16).CONCLUSIONS AND RELEVANCE Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Ou...

Background Reliable biomarkers predictive of venous thromboembolism (VTE) after acute trauma are uncertain. The objective of the study was to identify risk factors for symptomatic VTE after trauma, including individual plasma coagulome characteristics as reflected by thrombin generation. Methods In a prospective, case-cohort study, trauma patients were enrolled over the 4.5 year period, 2011–2015. Blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and at hospital discharge. Platelet poor plasma was stored at −80°C until analysis. Thrombin generation, as determined by the calibrated automated thrombogram (CAT) using 5 pM tissue factor (TF)/4 uM phospholipid (PS), was reported as peak height (nM thrombin) and time to peak height (ttPeak [minutes]). Data are presented as median [IQR] or hazard ratio (HR) with (95% CI). Results Among 453 trauma patients (ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=49 [28, 64] years, 71% male, 96% with blunt mechanism, mortality 3.2%), 83 developed symptomatic VTE within 92 days after injury (35 [42%] after hospital discharge). In a weighted, multivariate Cox model that included clinical and CAT characteristics available within 24 hours of admission, increased patient age (1.35 [1.19,1.52] per 10 years, P<0.0001), body mass index (BMI) ≥ 30 kg/m2 (4.45 [2.13,9.31], p <0.0001), any surgery requiring general anesthesia (2.53 [1.53,4.19], P=0.0003) and first available ttPeak (1.67[1.29, 2.15], p <0.00001) were independent predictors of incident symptomatic VTE within 92 days after trauma (C-statistic=0.799). Conclusion The individual’s plasma coagulome (as reflected by thrombin generation) is an independent predictor of VTE after trauma. Clinical characteristics and ttPeak can be used to stratify acute trauma pts into high and low risk for VTE.

Objective The two sides of Trauma Induced Coagulopathy (TIC), the hypo- and the hyper- coagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant MPs and thrombin activity during hospitalization for trauma. Methods Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and discharge. Platelet poor plasma was harvested and stored at −80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lagtime (minutes), peak height (nM thrombin) and time to reach peak height (ttPeak - minutes). The concentration of total procoagulant MPs (number/uL]) was measured by flow cytometry. Data are presented as median [interquartile range]. Results Among 443 trauma patients (1734 samples; ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=48 [28, 65] years, 70.7% male, 95% with blunt mechanism, mortality 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 [285, 395] nM and 400 [211, 772] per uL plasma, respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible “hypercoagulable state” (lagtime ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2278) were reached within 12 hours after acute trauma, while extreme values representing a possible “hypocoagulable state” (lagtime ≥ 18.6, peak height ≤ 17.8 and ttPeak ≥ 29.45) were not reached until 1-3 days. Conclusion Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters.