CRASH-2 was a massive, international undertaking, testing the utility of tranexamic acid to improve outcomes in bleeding trauma patients. When given with 3 hours, there were significant reductions in mortality due to bleeding – and the current push for its widespread use was born.
However, this study, and others like it, is not seeing the same magnitude of success as described in CRASH-2. This single-center, retrospective evaluation of trauma patients reviewed the mortality benefit associated with implementation of a thromboelastography-based TXA protocol. In 2011, this institution introduced a TEG-based TXA threshold of estimated percent lysis at 30 minutes of >3.0%, and these authors reviewed all cases of trauma patients between 2009 and 2013 meeting that threshold and eligible for treatment within 3 hours.
These authors identified a cohort of 98 patients who met criteria and received TXA, and compared them with a cohort of 934 patients who met criteria and did not. In-hospital mortality in the cohort receiving TXA was double those who did not (40% vs. 17%), and this disadvantage persisted despite adjustment for age, gender, mechanism, ISS, hypotension, and base excess. TXA usage was also not associated with resolution of hyperfibrinolysis, as measured by follow-up TEG, but neither was it associated with an increase in thromboembolic events.
Unfortunately, this retrospective evaluation is biased by confounding and unmeasured selection imbalances. It is, however, not the only study questioning the value of TXA in the setting of routinely well-resuscitated, modern trauma evaluation. Nothing in this small review provides compelling evidence regarding cessation or tailoring of TXA therapy in bleeding trauma patients, but it does support its continued evaluation for its role in organized, modern trauma settings.
“The impact of tranexamic acid on mortality in injured patients with hyperfibrinolysis”
Despite the study many major concerns arused about CRASH 2. I am aware at least of 3 major of them
1. Fewer than 2% of the patients in CRASH-2 were treated in countries that routinely provide rapid access to blood products, damage-control surgery and angiography, and advanced critical care.
2. Unanswered question about safety of TxA when combined with other treatments targeting bleeding and coagulopathies.
3. Unanswered question wich patients should receive TXA
In my opinion new and more accurate studies are needed build more solid evidences
Ryan,
I like your measured conclusion regarding this paper. As you say, a small study of inferior design should not trump a well performed multi-center large randomized controlled trial.
For me, my default is still to give TXA in suitable trauma patients. I think it is pretty darn safe and might help a little. It is certainly no replacement for good overall trauma care. I completely understand the issues of external validity regarding CRASH 2. I will wait for the good quality studies in developed trauma systems before I change my mind.
The funny think is TXA is dirt cheap and not being flogged by some pharmaceutical company. If it was expensive we would all be writing with TXA pens while talking about the "saving trauma campaign" at our next EM conference.
I guess we will know more in the coming years. But as you mention, this small confounded study should not really change things.