Joint U.S.-British Study Supports Military Application of Drug to Reduce Post-Trauma Bleeding

By Tiffany Holloway

Hemorrhage is the leading cause of death in civilian and military trauma. Fortunately, there is hope, in the form of tranexamic acid (TXA), a synthetic derivative of the amino acid lysine. Through the United States’ Joint Theater Trauma System, which is an organized approach to providing improved trauma care across the continuum of levels of care, especially in the battlefield environment, TXA was recognized after years of observations.

There was level 1 evidence in the Clinical Randomization of an Anti-fibrinolytic in Significant Haemorrhage 2 (CRASH-2) trial for the use of TXA, including a purported survival benefit in civilian trauma patients. However, the existing study performed on TXA was in a civilian population; the study took place in third-world countries where modern-day transfusion techniques were not applied nor did the patients receive any units of blood.

“This study prompted a spirited debate,” said COL Todd Rasmussen, Deputy Commander of the U.S. Army Institute of Surgical Research and Chief of the San Antonio Military Vascular Surgery Service.

Military surgeons, civilian surgeons, and academics met for months at various conferences, and the consensus was to not use TXA.

“Even though we, as the United States’ combat casualty care system, decided not to use TXA, there was evidence that it was working and that it was safe. There was some discomfort. We were torn between using it and not using it. That’s what happens in science. We needed to see whether or not TXA was clearly applicable.

“So we decided to do a retrospective cohort study,” said Rasmussen. “The British were using TXA and were interested in seeing how well it was working, and we in the United States had an interest because at Camp Bastion in Helmand Province, Afghanistan, the British were treating select U.S. troops with TXA as part of their resuscitation strategy.”

“The benefit of the retrospective cohort study is that it targets the exact population that wasn’t available in the CRASH-2 trial study,” said Dr. Kenji Inaba, Assistant Professor of Surgery and Medical Director of the Surgical Intensive Care Unit at the University of Southern California.

The retrospective cohort study was performed on patients who had been treated at Camp Bastion. Using the Joint Theater Trauma Registries of the two countries, two consecutive years of clinical data was reviewed, focusing on patients receiving at least one unit of blood within 24 hours of a combat-related injury. This included information on U.S. troops treated at the United Kingdom (U.K.) facility, said Rasmussen.

The study compared several endpoints, including survival, between patients who received TXA and those who did not. Of approximately 1,000 patients, nearly 300 were U.S. troops.

“This study was the first international collaboration of its kind and required the U.S. IRB [Institutional Review Board] approval, as well as approval from the U.K.’s Ministry of Defense Research Ethics Committees. We sent select U.S. researchers to the U.K. Joint Medical Command Research Pillar to work with U.K. researchers using their trauma registry. Subsequently, the U.K. sent surgical researchers to the U.S. Army Institute of Surgical Research to work with the U.S. Joint Theater Trauma Registry,” said Rasmussen.

The result of this groundbreaking international military collaboration is a study referred to as the MATTERs, for Military Application of Tranexamic Acid in Trauma Emergency Resuscitation Study. This study concludes that the use of TXA as part of a blood component resuscitation after wartime injury provides a survival advantage, most notably in patients receiving larger amounts of blood. Preliminary results from the MATTERs study show few, if any, serious complications identified with the use of TXA, although Rasmussen was quick to add that “prospective study of the use of TXA is needed to more fully define its safety profile.”

“Retrospective study methodology is by no means perfect, and further investigation is and will be performed to determine the extent of effectiveness of TXA. However, this study was implemented in a fairly expeditious manner, and as a result, the effects of saving lives can start now rather than years later,” he said.

“Any product that is demonstrated to decrease bleeding with improved outcomes at an acceptable cost and with an acceptable risk profile will potentially benefit injured patients—both military and civilian,” Inaba said.

[Editor’s Note: The Joint Theater Trauma System Clinical Practical Guideline has been updated based on the findings of the MATTERs study to support the use of TXA in theater.]


  • TIFFANY HOLLOWAY is the Deputy Public Affairs Officer at the U.S. Army Medical Research and Materiel Command. She holds a B.A. in journalism from Auburn University Montgomery and an M.A. in public relations from Webster University.

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