A systematic review of antifibrinolytics and massive injury

Every year, more than a million people die as a result of trauma. This huge mortality could be partially explained by the development of an acute traumatic coagulopathy, present in a large part of all major trauma patients, soon after injury, which contributes to ongoing hemorrhage. The coagulopathy induced by trauma is independently associated with mortality, increased transfusion requirements, multiple organ dysfunction, infections, increased intensive care unit (ICU) length of stay, and costs. The pathophysiological mechanisms implicated in this acute traumatic coagulopathy are complexes and lead to generate a vicious circle leading to the activation of different pathways: thrombin generation, plasmin generation, inflammation activation. All of these processes will impair the balance between clot formation and clot lysis, with an increased tendency of hyperfibrinolysis. In 2010, the CRASH-2 trial demonstrated that tranexamic acid (TXA) administration was associated with a reduction in all cause mortality (14.5% vs. 16%, P=0.0035), including the risk of death due to bleeding (4.9% vs. 5.8%, P=0.0077), without an increase in fatal or non-fatal vascular occlusive events. Finally, the CRASH-3 trial is now recruiting patients with traumatic brain injury without extracranial bleeding. This study aims at determining the safety and efficacy of TXA administration in this particular setting. Our experience from the cardiac surgery setting highlighted a dose-dependent increased seizure incidence associated with the administration of TXA. For this reason, further studies are needed to better define the "optimal" dose scheme based on pharmacokinetic and pharmacodynamic studies.