Tranexamic acid corrects fibrinolysis in the presence of acidemia in a swine model of severe ischemic reperfusion

J Trauma Acute Care Surg. 2014 Mar;76(3):625-32; discussion 632-3. doi: 10.1097/TA.0000000000000143.

Abstract

Background: Tranexamic acid (TXA) is an antifibrinolytic with anti-inflammatory properties associated with improved outcomes when administered to trauma patients at risk for bleeding; however, its efficacy is unknown in acidemia. We evaluated the efficacy of TXA on hyperfibrinolysis using an established porcine traumatic hemorrhage ischemic shock model.

Methods: Ten Yorkshire swine underwent a controlled hemorrhage followed by supraceliac aortic cross-clamping. During standard resuscitation, control animals received recombinant tissue plasminogen activator (rtPA) after cross-clamp removal, and experimental animals received rtPA followed by TXA. Rotational thromboelastometry analysis was performed at baseline, 5 minutes and 15 minutes after rtPA dosing, and 4 hours after cross-clamp removal.

Results: Control and experimental animals had similar hemodynamics and routine laboratory values at baseline and throughout resuscitation. At the time of TXA administration, average pH was 7.2. Clot formation time was prolonged from baseline and all resuscitation time points in both groups, with no difference at any time point. Maximum clot firmness decreased from baseline at all resuscitation time points in both groups. Maximum lysis increased from baseline (9% control vs. 9% TXA) after tissue plasminogen activator administration in both groups (100% control vs. 99% TXA). In experimental animals, maximum lysis returned to baseline 10 minutes after TXA administration (92% vs. 9%, p < 0.001).

Conclusion: TXA rapidly and fully reverses hyperfibrinolysis despite severe acidemia in a porcine trauma model. TXA is a promising adjunct to trauma resuscitation that is easily administered in austere or prehospital settings.

MeSH terms

  • Animals
  • Antifibrinolytic Agents / therapeutic use*
  • Disease Models, Animal
  • Fibrinolysis / drug effects*
  • Recombinant Proteins / therapeutic use
  • Resuscitation / methods
  • Shock, Hemorrhagic / complications*
  • Shock, Hemorrhagic / drug therapy
  • Swine
  • Thrombelastography
  • Tissue Plasminogen Activator / therapeutic use
  • Tranexamic Acid / therapeutic use*
  • Water-Electrolyte Imbalance / drug therapy*
  • Water-Electrolyte Imbalance / etiology

Substances

  • Antifibrinolytic Agents
  • Recombinant Proteins
  • Tranexamic Acid
  • Tissue Plasminogen Activator