After the military showed benefit of tranexamic acid (TXA) in trauma, it was successfully tested in the large CRASH-2 trial, showing great benefit in civilians as well. Moving back to war zone trauma, MATTERs – Military Application of Tranexamic acid in Trauma Emergency Resuscitation Study – brings additional evidence that TXA is good for your trauma patient – and that the greatest benefit is in the most injured patients receiving massive transfusions.
This was a retrospective study, looking at military trauma patients from 2009-2010 requiring transfusion. In this time frame TXA was at first optional, and after 2010 implemented for patients receiving blood products or with sign of fibrinolysis on ROTEM. Later, of course, TXA has since been instituted for all major trauma suspected of bleeding as per CRASH-2.
The CRASH-2 protocol is TXA 1g as soon as possible (and within 3 hours of the injury). Then, another 1g as an infusion over the next 8 hours. We wrote about CRASH-2 a few years back here (Swedish text). This military trial used TXA 1g bolus, only repeated if the clinician felt it necessary. No-one really knows the optimal dose to use or at what infusion rates, but the CRASH-2 protocol has shown its worth, so I guess we’re sticking with it for now.
896 patients admitted with combat injury requiring transfusion. 293 received TXA and 603 didn’t. Looking at the MATTERs data, these are serious trauma patients! ISS around 25, and over 300 patients got massive transfusions, receiving an average of over 20 PRBCs.
Other usual suspects
Looking at the data, more of the patients receiving TXA also recieved cryoprecipitate. This makes sense, as TXA was on indication, these patients would also often receive other coagulo-enhancing drugs. It also fits with the TXA given to more of the massive transfusion patients and the TXA group looking slightly sicker. As TXA became more popular with time, there might be other advances in trauma care helping the patients in the TXA group. Still, the major difference between the two groups seems to be TXA.
When considering all patients in this study, the TXA group had a 17% mortality vs 23% for the no-TXA group. That’s already impressive. Graphs below.
Left graph showing cumulative survival for TXA vs no TXA for all patients – but look at just the ones needing massive transfusions (right graph), and you’ll find the TXA group has kept roughly the same mortality: 14%, while the no TXA mortality has increased to 28%! The relatively small cohort probably makes the statistical illusion of the hardest injured TXA patients having a better survival than the overall TXA survival. At best, it should be the same.
Any downsides? We’ve all been surprised TXA has shown so few thromboembolic complications. In this study, more patients got pulmonary embolisms and DVTs. Around 2-3% risk of PE or DVT in the TXA group vs 0% in the no TXA group.
This trial is adding to the evidence of TXA benefit, and also showing TXA might have the highest benefit in the most severely bleeding patients.