Administration of tranexamic acid is associated with reduced need for blood transfusions in major noncardiac surgeries but not increased risk of venous thromboembolism, according to a multicenter, randomized, placebo-controlled trial.

In the study, which examined more than 8000 patients undergoing various major surgeries across 10 Canadian hospitals who received either tranexamic acid or placebo, 7.4% of patients who received tranexamic acid received a blood transfusion, compared with 9.8% of patients who received placebo. The rate of venous thromboembolism was similar for both groups.

The findings, from the Tranexamic Acid to Reduce Transfusion in Major Noncardiac Surgery (TRACTION) trial, were published June 10 in the New England Journal of Medicine. 

Potential for Cost Savings

“Tranexamic acid is cheap and easily accessible, could be implemented globally, and has the potential for cost savings,” study author Brett L. Houston, MD, PhD, hematologist and clinician scientist at the University of Manitoba and CancerCare Manitoba in Winnipeg, told Medscape News Canada. “But adoption of a policy of giving tranexamic acid among hospitals has been variable, in part because of concerns about blood clots, particularly in patients with cancer or other prothrombotic conditions.” 

The researchers sought to determine whether a broad application of this medication could benefit patients that have not been considered eligible for tranexamic acid. They used a cluster-crossover trial design to randomly assign hospitals to a hospital-wide policy of intraoperative tranexamic acid or placebo for 4 weeks and then to switch medications for another 4 weeks. To be included in the study, the hospitals had to perform at least 100 noncardiac surgeries per month, and hospital leadership had to agree to participate in the policy. 

Eligible participants were adults undergoing open surgeries lasting at least 3 hours with a 5% or greater transfusion risk, Houston said. Patients received a bolus at the start of surgery and a second dose at the anesthesiologist’s discretion. 

The investigators evaluated 8273 patients. Of these, 5002 (60.5%) underwent oncologic surgery. Among the 4156 patients in the tranexamic acid group, 306 (7.4%) received a blood transfusion during hospitalization. Among the 4117 patients in the placebo group, 403 (9.8%) needed a blood transfusion. Venous thromboembolism within 90 days occurred in 2.1% of patients in both groups, meeting the criterion for noninferiority.

No Increase in Blood Clots 

“We were able to show that tranexamic acid reduces red blood cell transfusions in hospital, but I think perhaps equally important or even more important to some people is that we were able to demonstrate that it does not increase blood clots,” said Houston.

“Our trial was designed to address this question and will hopefully provide the necessary reassurance that tranexamic acid does not cause dangerous blood clots when used in major noncardiac surgery,” she added. “We hope that the TRACTION trial provides the evidence needed to incorporate tranexamic acid into perioperative policies, like many hospitals standardize antibiotics on call to the operating room or deep vein thrombosis prophylaxis postoperatively. A hospital policy of tranexamic acid use during major noncardiac surgery would facilitate broad, standardized adoption.”

In an accompanying editorial, Michael F. Murphy, MBBS, MD, consultant hematologist at Oxford University Hospitals in the United Kingdom, and Ian Roberts, MBBCh, PhD, professor of epidemiology and public health at the London School of Hygiene and Tropical Medicine, wrote that the further evidence from the TRACTION trial of the safety and effectiveness of tranexamic acid in surgery should encourage its more widespread use.

“Most patients don’t want blood transfusions. If you can avoid it, you would, so this is great news from another big trial from Canada that showed this drug reduces bleeding and reduces the need for blood transfusion,” Roberts told Medscape News Canada. Still, even with this knowledge, not enough patients are getting the treatment. “In the UK, at least a third and possibly a half of patients who should get tranexamic acid don’t get it,” he said.

Tranexamic acid is safer than blood, Roberts added. “Doctors are too relaxed about blood; they think blood is safer than it really is and they are too worried about tranexamic acid, thinking it is way riskier than it really is. They should think of safely avoiding blood transfusion by giving an alternative that is much safer,” he said.

Tranexamic acid is a cheap generic drug with significant patient benefits but little financial benefit for drug companies, Roberts added. “It’s got huge benefits for the healthcare provider because blood is expensive, and patients who bleed more stay in hospital longer and get more complications. So tranexamic acid is good for the hospital and good for the patient but not particularly good for the pharmaceutical industry, and they are the ones who so often tell doctors what to do,” he said. 

Then there is the blood industry, Roberts said. “In general, the blood industry tells the public that their blood can be life-saving and convince the public to donate it for free, and then they sell it to hospitals, they fractionate it to get all the expensive things out of it, and then they sell those, so it’s quite a nice business model: Get something for free and then sell it. I think there is a vested interest within the transfusion industry to not pay enough attention to things that reduce the need for blood transfusion because that is not in their financial interest.”

The study was funded by the Canadian Institutes of Health Research; Health Sciences Centre Foundation; Government of Manitoba through the Ministry of Health, Seniors and Long-Term Care; and the Ontario Ministry of Health’s Innovation Fund. Houston and Roberts reported no relevant financial relationships.