Tranexamic Acid: What You Should Know

Trauma can be messy. The scene after a good trauma case is most likely littered with empty bags of crystalloid and the plastic wrappers of dressings and IV catheters. And blood. Lots of blood.  For severe trauma patients that make it to a trauma center, exsanguination is a common cause of death. What else can be done beyond direct pressure, hemostatic gauze, and early tourniquet application (assuming the injury is even in a tourniquet-able location)? How can a patient be resuscitated without fluid boluses that turn their blood to Kool-Aid on your ambulance floor? Blood products are certainly an answer, but this is wholly impractical for your average ground EMS unit. 

The possible answer: Tranexamic Acid (TXA).  TXA is simply a synthetic analogue of the amino acid lysine.  It is given intravenously (also available for enteral use non-emergently), and acts as an antifibrinolytic.  TXA has actually been around for years in the cardiac surgery world, but has only recently been adopted by trauma centers and some EMS systems.  It is not a procoagulant which is vital to its incredible safety profile.  Rather than making blood clot, it stabilizes already formed clots and prevents clot breakdown.  In short, plasmin is a protein that begins the breakdown of a clot’s fibrin matrix when activated; lysine prevents its activation by blocking the necessary enzymes.   By flooding the circulation with synthetic lysine, we can stop this fibrin breakdown systemically.  As a result, clots are not forced to form so there is no significant increase in thrombo-embolic complications, like stroke, MI, and pulmonary embolism.

Extensive research on the early administration shows that although it may not prevent massive vessel or visceral hemorrhage, the use of TXA increases survivability by slowing moderate bleeding and reducing the need for resuscitative blood transfusion by around 33% (Reed, 2013).  The two landmark trials that prove the efficacy and safety of TXA in traumatic hemorrhage are the “Clinical Randomization of an Antifribrinolytic in Significant Hemorrhage 2” (CRASH-2), and the “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation Study” (MATTERs).

CRASH-2 was a large multi-site study that included 274 hospitals in 40 countries and enrolled a staggering 20,000 + adult trauma patients. All had significant bleeding and criteria we would refer to as “shock-y”.  The treatment group was given 1 g IV TXA over 10 minutes and a second dose over 8 hours. The study concluded with a statistically significant finding of a reduction of mortality and advocated the administration of TXA within 3hrs of injury.  The safety of the drug was prominently addressed and showed no differences in instances of thrombo-embolic complications between the treatment and placebo groups. However, it did show that administration after the three hour mark post-injury actually INCREASED bleeding and morbidity/mortality.

MATTERs was the military companion to the CRASH-2 study and was conducted primarily in combat hospitals in Afghanistan. It was published prior to CRASH-2 and helped provide basis for increased civilian use of TXA and continuation of the massive CRASH-2 trial.  MATTERs showed an even greater reduction in mortality in the treatment group, with 17.4% mortality compared to the placebo group’s 23.9% mortality.  The added component of a massive transfusion sub-group saw an added 50% reduction in mortality with TXA.  These findings show that the use of TXA with a blood component based resuscitation after a traumatic injury can improve coagulopathy and increase survival.

For a more exhaustive assembly and analysis of everything we know now about TXA in trauma, check out the Napolitano review article in the references.  But for our purposes, here are some take-home points.  TXA is a drug that has been around for many decades, but its use in trauma is just now being fully recognized and evaluated.  For the bleeding or potentially bleeding trauma patient, it is dosed at 1 gram IV over 10 minutes, and then another 1 gram IV given over 8 hours.  It is most effective if the first dose is given less than one hour from the time of injury, and it is actually harmful if given past the 3 hour mark.  Otherwise, the drug has an impressive safety profile, and most suppliers offer the drug for cheap.  Hopefully we will all be seeing this on street EMS units in the near future.  

 

References

Morrison JJ, DuBose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. Feb 2012; 147(2): 113-119.

Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma: How should we use it? J Trauma. Jun 2013; 74(6): 1575-1586.

Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, Cook L, Kawahara T, Perel P, Prieto-Merino D, Ramos M, Cairns J, Guerriero C.  The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. Mar 2013; 17(10).

Vu EN, Schlamp RS, Wand RT, Kleine-Deters GA, Vu MP, Tallon JM. Prehospital use of tranexamic acid for hemorrhagic shock in primary and secondary air medical evacuation. Air Med J. Sep 2013; 32(5): 289-292. 

Photo accessed from http://i.imgur.com/VMSQBxq.jpg