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 context of severe trauma, this system can be hypo-and hyper-activated to varying extents, which can be appreciated in trauma-induced coagulopathy and is associated with poor outcome. Anti-fibrinolytic drugs including tranexamic acid (TXA) are currently used successfully in trauma, elective surgery, gynaecology and various other indications to reduce bleeding complications. In trauma, administered within 3 h post-injury, TXA was demonstrated to reduce all-cause mortality and mortality due to bleeding, whereas later administration was surprisingly deleterious. This may be explained by a counterintuitive effect of TXA on plasminogen under certain conditions. Moreover, while trauma practitioners have embraced the use of TXA, uncertainty still exists about its thromboembolic potential and the benefit to different subpopulations of trauma patients. Recent clinical trials further support the safety profile of TXA, and open questions regarding the use of TXA are currently being addressed in ongoing randomized controlled trials (RCTs).