Tranexamic Acid in Trauma Care

Tranexamic Acid Update in Trauma

• Tranexamic acid (TXA) is a synthetic lysine derivative, previously shown effective in reducing blood loss in several surgical procedures.
• TXA improves mortality in bleeding trauma patients when administered within 3 hours of injury, but doesn't reduce blood product transfusions.
• Pharmacokinetics and optimal dosing in trauma patients are still unknown.
• Further research is needed to refine current understanding of TXA's mechanisms of action in trauma patients and optimize drug administration.

Introduction to Trauma

• Trauma is a leading cause of death and disability worldwide, with an estimated 5.8 million deaths annually due to traumatic injury.
• Hemorrhage is the most common cause of preventable death after traumatic injury, in both military and civilian settings.
• Antifibrinolytic agents, like TXA, have gained interest for preventing hemorrhagic death in severe trauma.
• The CRASH-2 and MATTERs studies were landmark trials demonstrating TXA's potential mortality benefit in civilian and military trauma.

Background on TXA

• TXA acts by competitively occupying the lysine binding site of plasminogen, blocking interaction with fibrin, thus preventing clot breakdown.
• TXA has a molecular weight of 157.2 g/mol and is marketed as Cyklokapron.
• In healthy individuals, peak plasma concentrations following a 10mg/kg dose are achieved in 60 minutes, with a half-life of approximately 2 hours.
• About 90% of TXA is excreted within 24 hours.
• TXA crosses the placenta and is present in breast milk and synovial fluids.

Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) Trial

• A randomized, placebo-controlled trial conducted in 40 countries involving 20,211 adult trauma subjects.
• The study demonstrated a 14.5% reduction in overall in-hospital mortality (within 4 weeks of injury) in the TXA group compared to the placebo group.
• TXA administration within 1 hour of injury offered the greatest mortality reduction; treatment between 1 & 3 hours reduced risk, while treatment after 3 hours increased mortality risk.
• The study suggested that risk of death from bleeding was multiplied by 1.15 (95% CI 1.08-1.23) for each hour delaying treatment after injury.

Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study

• A retrospective observational study evaluating TXA in combat-related injuries.
• The study involved 896 admissions and assessed mortality at 24 and 48 hours, as well as 30-day, in-hospital mortality.
• Tranexamic administration was associated with reduced 17.4% in-hospital mortality compared to 23.9% in the control group.
• This difference held true in more severely injured patients.
• An association with thromboembolic events was also observed, though not independently linked after multivariate analysis.

Role of Fibrinolysis in Trauma

• Acute traumatic coagulopathy (ATC) involves disturbed hemostasis and high fibrinolysis, frequently present in trauma patients.
• It stems from imbalanced hemostasis and fibrinolysis caused by tissue damage.
• Up to 46% of severely injured patients display fibrinolysis shutdown, a condition that may affect TXA efficacy.
• Three distinct fibrinolytic phenotypes exist: shutdown, physiologic, and hyperfibrinolysis.

Proposed Mechanisms of Action of TXA in Trauma

• TXA inhibits plasmin formation by binding to lysine binding domains on plasminogen.
• Decreased plasmin levels hinder clot lysis.
• TXA likely affects not only clot lysis, but also inflammatory and immune responses.

Tranexamic Acid Use in Children

• TXA use for children has been studied in various surgical settings (orthopedic, cardiac, craniofacial), demonstrating effectiveness in reducing blood loss.
• Despite evidence in adult trauma, fewer studies exist for pediatric trauma patients.
• TXA dose for children may vary from 25-50 mg/kg IV bolus, with no clear guidelines regarding administration in cases of trauma.

Treatment Complications

• TXA use may lead to seizures, particularly with high doses.
• TXA can readily cross the blood-brain barrier, potentially affecting clotting and brain function.
• Some studies suggest TXA can increase cerebral ischemia and microvascular thrombosis in cases like subarachnoid hemorrhage (SAH).

Areas of Ongoing Research

• Several ongoing clinical trials (STAAMP, TAMPITI, Prehospital TXA Use for TBI Trial) aim to further elucidate the role of TXA in specific trauma situations and conditions like severe traumatic brain injury (TBI).
• Studies are still underway to understand the impact of TXA on immune system responses in trauma patients.