Background Fibrinolysis shutdown(SD) is an independent risk factor for increased mortality in trauma. High levels of plasminogen activator inhibitor-1(PAI-1) directly binding tissue plasminogen activator(tPA) is a proposed mechanism for SD, however patients with low PAI-1 levels present to the hospital with a rapid TEG(rTEG) LY30 suggestive SD. We therefore hypothesized that two distinct phenotypes of SD exist, one, which is driven by tPA inhibition, while another is due to an inadequate tPA release in response to injury. Methods Trauma activations from our level-1 center between 2014 to 2016 with blood collected within an hour of injury were analyzed with r-TEG and a modified TEG assay to quantify fibrinolysis sensitivity using exogenous tPA(t-TEG). Using the existing rTEG thresholds for SD(<0.9%), physiologic(LY30 0.9–2.9%), and hyperfibrinolysis(LY30 >2.9%) patients were stratified into phenotypes. A t-TEG LY30 > 95th percentile of healthy volunteers(n=140) was classified as tPA hypersensitive and used to sub-divide phenotypes. A nested cohort had tPA and PAI-1 activity levels measured in addition to proteomic analysis of additional fibrinolytic regulators. Results This study included 398 patients (median NISS 18), tPA-Sen was present in 27% of patients. Shutdown had the highest mortality rate(20%) followed by hyperfibinolysis(16%) and physiologic(9% p=0.020). In the non-tPA hypersensitive cohort, SD had a 5-fold increase in mortality(15%) compared to non-SD patients(3% p=0.003 figure) which remained significant after adjusting for ISS and age (p=0.033). Overall tPA activity (p=0.002) PAI-1 (p<0.001) and tPA/PAI-1 complex levels (p=0.006) differed between the six phenotypes and 54% of fibrinolytic regulator proteins analyzed (n=19) were significantly different. Conclusion In conclusion, acute fibrinolysis shutdown is not caused by a single etiology, and is clearly associated with PAI-1 activity. The differential phenotypes require an ongoing investigation to identify the optimal resuscitation strategy for these patients.

Introduction Tranexamic acid (TXA) administration following trauma has not been proven to improve survival in the US. Trauma patients present to the hospital with a spectrum of fibrinolytic activity, in which a physiologic levels of fibrinolysis are associated with the lowest mortality. We hypothesize that trauma patients who present to the hospital with physiologic levels of fibrinolysis will have increased mortality if they receive TXA. Material and Methods Severely injured trauma patients followed prospectively from 2014 to 2016 we included in the analysis. The patient’s first thrombelastography (TEG) was used to stratify patients into fibrinolysis phenotypes which included fibrinolysis shutdown, physiologic fibrinolysis, and systemic hyperfibrinolysis. The primary outcome was in hospital mortality. Results 232 patients were analyzed (11% received TXA) with an overall mortality rate of 20%. TXA administration was associated with a higher new injury severity score (NISS 49 vs 28 p=0.001) massive transfusion rate (69% vs 12% p<0.001) and mortality (52% vs 17% p<0.001). Hyperfibrinolysis and shutdown had higher mortality rates than physiologic (24% vs 30% vs 14% p=0.050). The effect of TXA within phenotypes, was not significant for shutdown (28% vs 38% p=0.604) but was significant in the physiologic group (11% vs 63% p<0.001) and systemic hyperfibrinolysis (19% vs 55% p=0.023). After adjusting for NISS, TXA remained a significant predictor of mortality for patients with physiologic fibrinolysis (p=0.018). Conclusion There was no clear benefit of receiving TXA in this study, and patients who present to the hospital with physiologic levels of fibrinolysis, who received TXA, had the highest mortality. The role of TXA in mature trauma systems remains unclear, and emerging data supports it may have adverse effects.

Early intubation for EI as well as DI was safe and effective. One third of the DI patients had significant head injury. Surgical airways were rarely needed and delayed intubations were uncommon. The intubation rates for EI and DI varied significantly among TSs. The Eastern Association for the Surgery of Trauma Guidelines may not identify all patients who would benefit from early intubation after injury.