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The acute coagulopathy of trauma is often accompanied by hyperfibrinolysis. Tranexamic acid (TXA) can reverse this phenomenon, and, when given early, decreases mortality from bleeding. Establishing intravenous (IV) access can be difficult in trauma and intraosseous (IO) access is often preferred for drug administration. Currently, there are no data on the efficacy of IO administered TXA. Our objectives were to compare serum concentrations of TXA when given IV and IO and to compare the efficacy of IO administered TXA to IV at reversing hyperfibrinolysis.Using a porcine hemorrhage and ischemia-reperfusion model, 18 swine underwent hemorrhagic shock followed by a tissue plasminogen activator infusion to induce hyperfibrinolysis. Animals then received an IV or tibial IO infusion of TXA over 10 minutes. Blood was then analyzed using rotational thromboelastometry to monitor reversal of hyperfibrinolysis. Serum was analyzed for drug concentrations.After hemorrhage and ischemia-reperfusion, there were no significant differences in mean arterial pressure (48 vs. 49.5), lactate (11.1 vs. 10.8), and pH (7.20 vs. 7.22) between groups. Intraosseous TXA corrected the lysis index at 30 minutes in EX-TEM and IN-TEM, like IV infusion. Peak serum levels of TXA after IV and IO administration show concentrations of 160.9 μg/mL and 132.57 μg/mL respectively (p = 0.053). Peak levels occurred at the completion of infusion. Drug levels were tracked for four hours. At the end of monitoring, plasma concentrations of TXA were equivalent.Intraosseous administration of TXA is as effective as IV in reversing hyperfibrinolysis in a porcine model of hemorrhagic shock. Intraosseous administration was associated with a similar peak levels, pharmacokinetics, and clearance. Intraosseous administration of TXA can be considered in hemorrhagic shock when IV access cannot be established.