Massive Transfusion And Tranexamic Acid (TXA)

Tranexamic acid has been in use for decades, just not for trauma. The CRASH-2 trial was a massive multi-country study showed that there was a slight mortality reduction from 16% to 14.5% in trauma patients who had or were at risk for “significant hemorrhage.” Moreover, there was no difference in vascular occlusive events, blood product transfusions, or need for surgery. Sounds great, right?

The MATTERs trial was initiated by the US military and tried to address some of the perceived shortcomings of CRASH-2 and found an absolute mortality reduction of 6.7%. But it also showed DVT rates that were 12x higher and PE rates 9x higher when this drug was given.

Since those two studies, a significant number of critiques have been published, as well as some additional research. Unfortunately, this has only served to cloud the picture. TXA is very inexpensive and readily available, so there has been a significant move to adopt both in the trauma center, as well as during prehospital care prior to arrival.

The trauma group at Denver Heath published a study of 232 patients with a 20% mortality rate from their injuries. They identified three subsets of patients based on their fibrinolytic response upon presentation to the hospital: physiologic fibrinolysis (49% of patients), hyperfibrinolysis (28%), and fibrinolytic shutdown (23%).

They found that mortality significantly increased in those receiving TXA who were physiologic or hyperfibrinolytic, but unchanged in those in shutdown. They cautioned that giving this drug before the patient’s fibrinolytic status was known could contribute to mortality.

Bottom line: So confusing! And many centers already include TXA in their massive transfusion protocol. Most have not seen unexpected mortality after giving the drug, so the jury is not in yet. Each trauma center should weigh the currently known pros and cons, and decide whether they are “believers” or not. Carefully review all mortalities and thrombotic complications after administration to see if there was any relation to the use of TXA.


  1. Massive transfusion protocols and the use of tranexamic acid. Current Opinion Hematol 25(6):482-485, 2018.
  2. Tranexamic Acid is Associated with Increased Mortality in Patients with Physiologic Fibrinolysis. J Surg Res 220:438-443, 2017.
  3. CRASH-2 Study of Tranexamic Acid to Treat Bleeding in Trauma Patients: A Controversy Fueled by Science and Social Media. J Blood Transfus Article 874920, 2015.
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