Cheap and battle-tested, TXA saves civilian lives
Tranexamic acid (TXA) is an anti-fibrinolytic that blocks the action of plasminogen, an enzyme that dissolves blood clots. It has been used for decades to minimize blood loss in planned surgeries, control oral bleeding in people with hemophilia and treat heavy menstrual periods.
In 2010, a British trial involving more than 20,000 people in 40 countries showed that TXA could also significantly reduce the risk of fatal bleeding events in trauma patients, potentially saving 128,000 lives each year.
Donald Jenkins, M.D., medical director for the Level I Trauma Center at Saint Marys Hospital, one of Mayo Clinic's hospitals in Rochester, Minn., says surgeons were skeptical at first.
"It was an interesting study, but left us scratching our heads," he says. "We didn't think there could be a big, new discovery about an inexpensive generic that had been around so long. And we questioned where and how the study was conducted. Some of the methods weren't particularly good."
Still, evidence for the drug's effectiveness was compelling enough that the World Health Organization added TXA to its essential drug list and the British military began using it for severely injured troops in Afghanistan. A follow-up study comparing TXA with standard hemorrhage treatment at the NATO facility in Bastion, Helmand Province, convinced most of the skeptics.
The Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study retrospectively evaluated nearly 900 casualties. "Two hundred and ninety-three of the most severely wounded received TXA," says Dr. Jenkins. "The others received traditional therapy. At 24 hours, there was no difference in mortality between the two groups, even though the TXA patients were much more badly injured. At day 28, mortality was substantially lower in the TXA group. And if you look at the patients who got massive transfusions, mortality in the TXA group was half that of the no-TXA group at the 28-day mark."
TXA is now routinely used by both the United States and Britain to treat severe wartime injury and hemorrhage. TXA has also made its way into a few civilian hospitals, including the University of Texas Health Science Center in Houston and, as of July 2, 2012, Mayo Clinic in Rochester, Minn., where the drug will be administered on Mayo One, Mayo's emergency medical helicopter service, as well as in the emergency department.
"We held off implementing TXA because we were waiting for a small amount of data," Dr. Jenkins explains. "We wanted to know how long reconstituted TXA remains sterile and stable because we'd rather mix it in the pharmacy than at the bedside. The Department of Defense found that vials of TXA could withstand freezing and heat up to 120 degrees. But what about once it's mixed with saline?"
He adds that if necessary, the drug can be mixed out of the vial during helicopter transport. "Other medications require that, and we know how to do it," he says.
Beat the clock
Current guidelines recommend that patients receive a 1-gram loading dose of TXA in the first three hours after injury, followed by intravenous infusion of another gram over eight hours. The earlier the initial dose is administered, the more likely it is to prevent fibrinolysis.
Dr. Jenkins notes, "Beyond the three-hour mark, there was an increased risk of complications like heart attacks. It's unclear why three hours is the break point. The mechanism isn't well understood, but there is diminished benefit and increased harm after three hours. We won't administer TXA if we don't have that window."
On the other hand, Dr. Jenkins doubts that patients who receive the first but not the second dose of TXA will experience problems. But he stresses that hospitals not using the drug should know how to treat patients who received it elsewhere. "TXA-treated patients should not get other clotting drugs," he says. "That is the real message. If you're not using the infusion, don't add prothrombin complex concentrate or recombitant Factor VIIa because of a high risk of complications."
Every hospital admitting a patient treated with TXA on Mayo One will receive a printed instruction card. But, Dr. Jenkins says, "We're trying to encourage other hospitals to use the drug. We know the sickest patients will benefit, both in the remote setting and in the hospital. And the patients who are treated soonest will benefit the most."