Antifibrinolytic Agent Saved Lives After Trauma
Drug prevents significant bleeding.
By Jenine Smith
Elsevier Global Medical News
Tranexamic acid, a cheap and widely available generic drug, has been shown to safely improve the chances of trauma patients surviving bleeding injuries, according to findings from a trial enrolling more than 20,000 patients in 40 countries.
The findings suggest that infusions of tranexamic acid, an antifibrinolytic agent used in surgery, also could be used in trauma care settings to help counter deaths from vehicular accidents and violence. Middle- and lower-income countries account for more than 90% of the world's trauma deaths, the study's authors noted.
For their research, an international group of investigators coordinated by Ian Roberts, Ph.D., professor of epidemiology and public health at the London School of Hygiene and Tropical Medicine, recruited 20,211 adult trauma patients from 274 hospitals, all of whom had or were at risk of developing significant bleeding. Many of the study centers were located in India, Latin America, and Africa, as "that's where so much of the trauma is," Dr. Roberts said in an interview. However, he added, tranexamic acid "is not a second-class treatment," but one appropriate to all settings.
Patients were randomized to receive either tranexamic acid (a loading dose of 1 g over 10 minutes followed by an infusion of 1 g over 8 hours) or placebo, with patients and clinicians blinded to treatment allocation.
Although the dosing of tranexamic acid in surgery is adjusted according to a patient's body weight, the study investigators decided on a fixed dose of 2 g, which is effective over a range of body weights, because of the difficulty of weighing patients in a trauma setting (Lancet 2010;376:23-32).
Tranexamic acid had been shown in randomized, controlled trials to reduce the need for blood transfusions by one-third in patients undergoing elective surgery (Cochrane Database Syst. Rev. 2007 [doi:10.1002/14651858.CD001886.pub2]), without increasing the risk of postoperative complications. The authors hypothesized that because the hemostatic responses to surgery and trauma are similar, tranexamic acid might reduce bleeding-related mortality in trauma patients as well.
The current study's primary outcome was death within 4 weeks of injury, whether from bleeding, vascular occlusion (myocardial infarction, stroke, and pulmonary embolism), multiorgan failure, head injury, or other causes, and analysis was by intention to treat.
All-cause mortality was shown to be significantly reduced with tranexamic acid: 1,463 (14.5%) of patients in the treatment group died within 4 weeks, compared with 1,613 (16%) in the placebo group.
The risk of death caused by bleeding was significantly reduced: 489 (4.9%) in the treatment arm, compared with 574 (5.7%) in the placebo arm.
"The results show that the early administration of tranexamic acid to trauma patients with, or at risk of, significant bleeding reduces the risk of death from hemorrhage with no apparent increase in fatal or nonfatal vascular occlusive events," the investigators concluded in their analysis.
The investigators did not see statistically significant differences in transfusion rates between the two groups--transfusions were given to 50.4% of patients in the treatment arm and 51.3% in the placebo arm.
One of the trial's limitations, the investigators acknowledged, was the fact it provided "limited insight into how tranexamic acid reduces the risk of death in bleeding trauma patients." However, they said, it is the first scientific evidence that it can save lives, and at about $9 per dose, "it would be considered a good buy in Boston or Bangalore," Dr. Roberts said. "You don't really get much cheaper ways to save a life."
Tranexamic acid is available in the United States as Cyklokapron and Lysteda. But despite the drug's affordability and generic status, it is not widely available in all countries and is still little known in trauma settings, Dr. Roberts said.
"There has been off-label use of this drug [for trauma] in the past but not a lot. It's something doctors are not doing, and if they do this tomorrow they could save millions of lives," he said.
Dr. Roberts said that his team had contacted the World Health Organization with the results of their study in an effort to have tranexamic acid added to WHO's Model List of Essential Medicines. "Many countries look to this as a shopping list," he said.
The study was funded by the U.K. National Institute for Health Research, Pfizer, BUPA Foundation, and the J.P. Moulton Charitable Foundation. The researchers reported that they had no conflicts of interest.
In an editorial, anesthesiologist Jerrold H. Levy of Emory University in Atlanta called the study "an important example of the complex relations between coagulation, fibrinolysis, inflammation, and outcomes after tissue injury. ... The similarities of tissue injury after trauma and surgery create a novel model for antifibrinolytic therapy with tranexamic acid."
However, Dr. Levy cautioned, the trauma findings from the tranexamic acid should not be extrapolated to other antifibrinolytic agents "until they have been studied in a similarly robust manner" (Lancet 2010;376:2-3).
Dr. Levy disclosed that he has received grants from and been an adviser to Novo Nordisk.