Tranexamic Acid in Civilian Trauma Care in the California Prehospital Antifibrinolytic Therapy Study

Michael M. Neeki, DO, MS; Fanglong Dong, PhD; Jake Toy, BA; Reza Vaezazizi, MD; Joe Powell, EMT-P; David Wong, MD; Michael Mousselli, BS; Massoud Rabiei, BS; Alex Jabourian, DO; Nichole Niknafs, DO; Michelle Burgett-Moreno, BA; Richard Vara, RN, BSN; Shanna Kissel, RN, MSN; Xian Luo-Owen, MD, PhD; Karen R. O'Bosky, MD; Daniel Ludi, MD; Karl Sporer, MD; Troy Pennington, DO; Tommy Lee, MD; Rodney Borger, MD; Eugene Kwong, MD


Western J Emerg Med. 2018;19(6):977-986. 

In This Article


In the United States (U.S.), traumatic injury is the leading cause of death and disability among those aged 1 to 44 years old.[1] Among trauma victims, hemorrhage accounts for 30% to 40% of the mortality.[2–4] Within the prehospital setting, hemorrhage is one of the top causes of death and comprises the largest portion of preventable deaths.[2,3] Significant blood volume loss leads to the depletion of coagulation factors and dysregulation of the coagulation system. Combined, these factors threaten the body's ability to maintain hemodynamic stability and may result in cardiovascular collapse.

The burden of trauma-induced coagulopathies (TIC) has been demonstrated in more than half of trauma patients following arrival to trauma centers and has been associated with a significant increase in the risk of trauma-induced mortality. [5–9] Historically, paramedics have not had access to medications that specifically target the reversal of TIC.[3,4] As biotechnological advances enable better detection and understanding of TIC, a group of patients has been identified that may benefit from early reversal of traumatic coagulopathies, leading to a possible reduction in associated mortality.[8,10–12]

Tranexamic acid (TXA) is a synthetic derivative that inhibits fibrinolysis and has been shown to be effective in the hospital setting in the treatment of hemorrhagic shock. In 2010 the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) trial suggested that TXA was associated with a 1.5% reduction (14.5% vs. 16%) in all-cause mortality at 28 days when administered within eight hours of injury without an increase in thromboembolic events.[13] In 2011 a post-hoc analysis showed that early TXA treatment within three hours from the time of injury in the hospital setting resulted in a 1.6% decrease in death due to bleeding; the reduction in mortality increased to 2.4% if administered within one hour from injury.[14]

Despite evidence surrounding hospital TXA use, a gap in knowledge exists surrounding the prehospital TXA use in the civilian setting. Multiple small studies have demonstrated the feasibility of prehospital TXA administration including the ability of paramedics to identify candidates with signs of hemorrhagic shock.[15–18] Two recent investigations focusing on civilian injuries in Germany and Japan further suggest that prehospital TXA use may reduce mortality in severely injured trauma victims. [19–20] However, their retrospective nature and the lack of standardized dosages and algorithms for TXA administration limited the generalizability of those studies. This paucity of out-of-hospital data has limited the widespread implementation of TXA into U.S. civilian prehospital-care protocols.

The California Prehospital Antifibrinolytic Therapy (Cal-PAT) study was designed to evaluate the safety and efficacy of TXA use in the civilian prehospital setting in traumatic hemorrhagic shock. A preliminary report during ongoing data collection from the Cal-PAT study was published in 2017.[21] This current study reports the final findings of the prehospital component of the Cal-PAT study. We hypothesized that the prehospital administration of TXA in cases of traumatic hemorrhagic shock would be associated with a decrease in mortality.