Anti-fibrinolytics

Abstract

The fibrinolytic system, driven by the plasminogen activator family of proteases, is widely known for its capacity to degrade fibrin and facilitate clot removal but also has a number of unrelated effects in the central nervous system (CNS). In the context of severe trauma, this system can be hyper-activated to varying extents and this is frequently observed in trauma-induced coagulopathy and is associated with poor outcome. Anti-fibrinolytic drugs including tranexamic acid (TXA) are currently used successfully in elective surgery and gynaecology to reduce bleeding complications. TXA, however, has been uniquely tested in recent years for its efficacy in patients who are bleeding or at risk of bleeding early after trauma. Administered within 3 h post injury, TXA reduced all-cause mortality and mortality due to bleeding, whereas later administration was surprisingly deleterious, but this may be explained by a counterintuitive effect of TXA on plasminogen under certain conditions. Moreover, while the trauma field has widely embraced the use of TXA, questions about its thromboembolic potential and the applicability for different subpopulations of trauma patients as well as the potential non-fibrinolytic consequences of plasmin blockade still remain and will be further assessed in ongoing clinical trials.