Abstract Topic: 33. Bleeding disorders (congenital and acquired)
Background: Tranexamic acid (TXA), an anti-fibrinolytic drug, can be used to reduce blood loss and transfusion need in surgery and trauma situations. However, overdosing of TXA can lead to hypofibrinolysis and thus a pro-coagulant state. Previous research has demonstrated the possibility to evaluate the dose-effect response of TXA with thromboelastography. The Lysis timer® (LT), a device developed by Biophen, is designed to determine the global fibrinolysis capacity (GFC) of patients in less than 1 hour.
Aims: The aim of our project is to determine the effective concentration (EC) of TXA using the GFC/LT, to facilitate TXA use in surgery or trauma.
Methods: Hyperfibrinolysis was induced by spiking citrated plasma with increasing concentration of Actosolv® (urokinase; uPA), from 0 to 5000 UI/mL. Our aim was to determine the optimal uPA concentration able to establish a hyperfibrinolysis model. Once this concentration was established, increasing concentrations of TXA (2.5 µg/mL – 100 µg/mL) were added to the uPA spiked citrated plasmas (n-4), and GFC measured. The EC50% and EC95% were determined using Graphpad Prism.
Results: The dose-response curve that allowed us to determine the optimal uPA concentration capable to induce a hyperfibrinolysis model is shown in figure 1a. We chose uPA of 125 U/ml. Next, increasing concentrations of TXA were added to 4 uPA spiked plasmas. The neutralization dose-response curve can be found in figure 1b. We found an EC50% at 12.7 µg/mL TXA and an EC95% at 66.1 µg/mL.
Summary/Conclusion: This study highlights the possibility to determine the TXA concentration able to neutralize hyperfibrinolysis in an in vitro setting, with potential clinical applications. We found that a concentration of 12.7 µg/mL TXA was sufficient to inhibit hyperfibrinolysis in 50% of 4 uPA spiked plasmas tested population. This corresponds to similar observations in other studies evaluating the TXA concentration using thromboelastography (Rozen et al, 2015). As the “optimal” TXA concentration required to completely inhibit fibrinolysis remains to be determined in clinic, we think that this method could be used to determine the minimal TXA concentration to inhibit hyperfibrinolysis in different urgent clinical settings (surgery, trauma, post-partum bleeding...). The limitation of our study is the low number of plasmas in our model. Further research is needed to reveal its in vivo applicability.
Keywords: Bleeding, Fibrinolysis, Therapy