Tranexamic Acid in Trauma

8070_tranexamic_acid100mgTranexamic acid is a medication that has been around for a while, but it has just started to gain momentum recently in the treatment of traumatic hemorrhage.  It is relatively cheap, and the data so far looks pretty promising.  You need to know the proper time limitations for giving the drug, however.  Tranexamic acid works by binding to the active site of plasminogen, inhibiting conversion to plasmin.  This results in decreased plasmin available and therefore decreased breakdown of clot already formed.  Decreasing the breakdown of fibrin already present theoretically results in decreased bleeding.  This has been proven true in various aspects of medicine, but only recently has the data begin to emerge advocating it’s use in trauma.  Most of the buzz about this that you will hear is from the CRASH-2 (Clinical Randomisation of Antifibrinolytic in Significant Hemorrhage).

This excellent study, published originally in the Lancet in March 2011, looked at over 20,000 trauma patients with risk of significant bleeding from 274 hospitals in 40 different countries.  Patients arriving to the center within 8 hours of injury were randomized to either the tranexamic acid arm or placebo arm.  The dose of tranexamic acid was 1g bolus IV over 10 minutes and 1 g subsequently over the next 8 hours.    The authors found interesting results.  If the tranexamic acid was given within one hour, the risk of dying due to hemorrhage was significantly reduced (5.3% vs 7.7%).  They also found a significant difference in the one to 8 hour group that received the tranexamic acid; they only had a 4.8% incidence of death due to bleeding, as opposed to 6.1% in placebo group. Both of these findings were statistically significant.  However, giving tranexamic acid AFTER 8 hours s/p injury resulted in an increased incidence of death due to hemorrhage compared to placebo (4.4% vs 3.1%), and this was also statistically significant.  The authors concluded that this should be given early in injuries where bleeding may be a major issue.

The MATTERs study by Morrison, et al is a retrospective observational study looking at injured soldiers who receive at least one unit of PRBCs with bleeding.  The TXA group had lower unadjusted mortality rates compared to not giving the medication (17.4% vs 23.9%), despite the TXA group having a higher injury severity score.  The noticed a larger improvement in the patients receiving massive transfusion (>10 units of PRBCs).  Although the study was retrospective, it analyzed a group of patients with more significant trauma as it was due to combat injury.

The studies on TXA will continue to be published in the next few years.  Keep an eye out for all of these.  As we increase the use of TXA, we will be able to learn more about the dosing and timing.  For now it does appear that giving TXA very early in the management of bleeding trauma improves outcomes, whereas giving it after 8 hours may harm the patient.

CRASH-2 trial collaborators, Shakur H, Roberts I, 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.

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

Cohen M, et al.  Coagulopathy associated with trauma.  Uptodate.com. Updated Dec 10, 2012.

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