Tranxemic Acid - Life Saver or Just another EMS Fad?

Almost 50 years ago scientists discovered that tranxemic acid (TxA) causes an inhibition of plasminogen to the active form or plasmin.  As a result fibrinolysis and clot breakdown was inhibited thus leading to a greater control over the loss of blood.  Originally, TxA was the treatment of choice  for patients with hemophilia as well as to decrease blood loss in patients undergoing oral surgery. Previous studies have shown it be very effective when given preoperative and as a result these patients have required much less whole blood during surgery.   Pre-hospital providers have jumped on the bandwagon of the heralding the importance of giving TxA in the field long before arrival at the hospital emergency department.  As a result of the CRASH 2 study (Shakur, et. al, 2010) a worldwide emphasis on the administration of the drug has become paramount.  However, there continues to be some gaps in the research when it comes to the efficacy and safety of the drug (Pusateri, et al. 2013). 

As a result of fibrinolysis, the progression of blood clot lysis starts when plasminogen is changed to plasmin.  This then begins the destabilization of formed blood clots (Ker, et al, 2013).  Because of this increased hemorrhage that can lead to death occurs.   Patients who receive TxA are physiologically prevented from the process of destabilization of this clot cascade.  A number of other large research studies have demonstrated that patient death is markedly lowered with TxA is given with a three hour window of initial insult of injury.  Large prospective randomized, controlled trials have shown that patient mortality is decreased when TXA is administered within three hours of injury (Yeguiayan et al, 2011).  The benefits markedly increase if given within the first hour of trauma Mortality was shown to decrease even more when it’s given within one hour (Brown, et al, 2009).   TxA has a low cost associated with it as well as minimal side effects.  One would assume that this would be a rapid approval as the standard of care for advanced life support paramedic agencies in the United States.  

Although TxA is a relatively old drug it was not used extensively until after the results of the CRASH-2 study.  This was a randomized, placebo controlled trial that looked at the effects of TxA on the morbidity and mortality of major hemorrhage of trauma patients.  It is well established that this hemorrhage is the primary cause of death, particularly in combat related injuries.  As a result a study completed by the army in 2011 showed that injured troops that were administered blood products during the time frame of 2009-2010 showed that the concurrent administration of TxA fared well.  According to the report, “For all patients requiring at least one unit of blood after combat injury, patients receiving TXA had higher rates of DVT (2.4% vs. 0.2%, p = 0.001) and PE (2.7% vs. 0.3%, p =0.001), but were also more likely to have injury patterns associated with higher risk of thromboembolic events ; including higher mean ISS (25 vs 23, p < 0.001), more severe extremity injuries (extremity AIS >=3 66.6% in TXA group, 47.3% non-TXA, p < 0.001), and more commonly GCS < or = 8 (63.3% vs. 35.6%, p < 0.001).” (Morrison, et. al, 2012). 

The administration of TxA would seem to without debate.  It is an extremely low cost solution to uncontrolled hemorrhage.  One study conducted in the United Kingdom showed the actual cost to be $64 per patient (Roberts, et al, 2013).  Long term side effects do not seem to be major as well.  Another study showed that the year death rate for patients receiving TxA was about the same as someone within the general population (Ker, et al, 2013)

In addition to a long shelf life and easy administration TxA should be on every ALS ambulance in the United States.  Unfortunately, this is not the case.  Although there are pockets of progressives who see the benefits of this potentially lifesaving medication, it is not widely used by civilian EMS agencies or hospitals in America.  It is time to rethink this standard and allow its use. 

References

Brown, MA, Daya, MR, Worley, JA. Experience with chitosan dressings in a civilian EMS system. J Emerg Med, 2009; 37(1): 1–7.

Ker K, Kiriya J, Perel P, Edwards P, Shakur H, Roberts I. Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial. BMC Emergency Medicine, http://www.biomedcentral.com/1471-227X/12/3.

Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Arch Surg, 2012; 147(2): 113–9.

Pusateri AE, Weiskopf RB, Bebarta V, et al. Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities. Shock 2013; 39: 121-126

Roberts I, Lockey DJ, Weaver AE, Davies GE. Tranexamic acid: A recipe for saving lives in traumatic bleeding. Int J Occup Environ Med, 2013; 53(4): 189.

Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376: 23-32.

Yeguiayan J, Rosencher N, Vivien B. Early administration of tranexamic acid in trauma patients. Lancet, 2011; 378(9,785): 27–8.

Published on May 06, 2016