Study Finds Tranexamic Acid Unable to Prevent Bleeding in Patients With Hematologic Malignancies

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In the first randomized trial to evaluate prophylactic antifibrinolytic therapy in patients with hematologic malignancies, tranexamic acid failed to reduce bleeding or the need for transfusion vs placebo. The study was featured as a Plenary Session during the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition.1

“Tranexamic acid, administered prophylactically in addition to routine platelet transfusion, did not decrease the rate of WHO [World Health Organization] grade 2 or greater bleeding in severely thrombocytopenic patients who were undergoing therapy for hematologic malignancies,” according to Terry B. Gernsheimer, MD, of the University of Washington, Seattle.

“It’s not a positive study, but we are positive about the results.”
— Terry B. Gernsheimer, MD

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In the multicenter randomized double-blind A-TREAT trial, the incidence of grade ≥ 2 bleeding (observable organ system bleeding, bleeding that requires minor intervention) was 48.8% with tranexamic acid plus transfusion vs 45.4% with placebo plus transfusion (95% confidence interval [CI] = 0.52–1.38), a difference that failed to achieve statistical significance.

Additionally, platelet and red blood cell transfusions did not differ between the arms. There was no difference in thrombotic events or mortality; an increased incidence of central line occlusion requiring clearing with tissue plasminogen activator (tPA) in the tranexamic acid arm was observed, she noted.

Dr. Gernsheimer said the results came as something of a surprise to the investigators. “I think we did expect, from our own observations in the past and from its usefulness in other situations, we would indeed see a difference between the arms. And mostly, we hoped to see a difference in the number of transfusions these patients required. None of that was true. It’s not a positive study, but we are positive about the results.”

Based on the findings, Lisa Baumann Kreuziger, MD, MS, of Versiti and Medical College of Wisconsin, maintained: “Tranexamic acid should not be routinely used as prophylaxis in nonbleeding patients with low platelet counts and hematologic malignancy.”


Although tranexamic acid is “not uncommonly” used to prevent bleeding, its efficacy has not been well evaluated, according to Dr. Gernsheimer. The aim of A-TREAT was to find an evidence basis for its use.

A-TREAT involved 330 patients (median age, 54) undergoing transplantation or chemotherapy for various hematologic malignancies. Within the population, 39% had an allogeneic transplant, 22% had an autologous transplant, and 39% received chemotherapy and/or immunotherapy. The median time on the study drug was 12 days.


  • The multicenter A-TREAT study evaluated the efficacy of the antifibrinolytic agent tranexamic acid in preventing bleeding among patients with hematologic malignancies.
  • No benefit was found for the drug vs placebo, given with transfusion.
  • Platelet and red blood cell transfusions did not differ between the study arms.
  • There was no difference in thrombotic events or mortality. More central line occlusions (without associated thrombus) occurred in the tranexamic acid arm.
  • Tranexamic acid should not be routinely used as prophylaxis in nonbleeding patients with low platelet counts and blood cancer.

Eligible patients were expected to have a platelet count less than 10,000/μL for at least 5 days. Patients were randomly assigned to tranexamic acid or placebo, initiated when platelet counts fell below 30,000/μL. Assigned treatment was discontinued after 30 days or platelet recovery to a platelet count of 30,000/μL; upon the occurrence of thrombosis, veno-occlusive disease, recurrent central line occlusions, or visible hematuria; by physician or patient request; or upon the initiation of open-label tranexamic acid.

The trial followed the standard practice of red blood cell transfusion at a hemoglobin of about 8.5 g/dL and a platelet count less than 10,000/μL. The primary endpoint was an incidence of grade 2+ bleeding by WHO criteria (observable organ system bleeding requiring minor intervention).

No Significant Treatment Effect

Tranexamic acid was associated with a 14% reduction in the risk for grade ≥ 2 bleeding, which did not achieve statistical significance (95% CI = 0.52–1.38). Bleeding was seen in 45.4% of the tranexamic acid cohort and 48.8% of the placebo group.

Analysis by subgroup (allogeneic transplant, autologous transplant, chemotherapy) yielded odds ratios of 0.71 to 0.94 favoring the drug, but none reached statistical significance. Analyses focusing on days without bleeding, platelet and red cell transfusions, and grade ≥ 3 bleeding also revealed no significant differences.

“Of note, the majority of patients in both groups had central line occlusions alone, without an associated thrombus,” Dr. Gernsheimer emphasized. “Also, in fact, fewer noncatheter-related thrombotic events were seen in the tranexamic acid group, though this was not statistically significant.” Patients assigned to tranexamic acid did not have a significantly higher rate of thrombotic events (3.7% vs 5.5%), although central line occlusions requiring tPA were increased (16.5% vs 6.7%).

The arms did not differ in terms of thrombotic events through 120 days (0.2% overall), veno-occlusive disease within 30 days of the last dose (1.5%), all-cause mortality at 30 days (2.7%) or 120 days (11.5%), and thrombosis-associated mortality at 120 days (0%).

Role in Other Settings Still Undetermined

This study evaluated tranexamic acid as an adjunct to routine prophylactic platelet transfusion in preventing bleeding. Its benefit in other settings of thrombocytopenia, such as in the treatment of active bleeding, refractoriness to platelet transfusion, or prophylaxis for procedures, cannot be ruled out, Dr. Gernsheimer acknowledged.

“Despite all our best efforts, bleeding remains a relatively common event in these patients, and these events are sometimes serious, life-threatening, or fatal,” she told journalists. “We clearly are not addressing what the major issue most likely is. Certainly, we’ve helped patients by using platelet transfusions, but I think we need to address other factors that may be present for bleeding, such as the endothelial damage we see with chemotherapy and graft-vs-host disease.” 

DISCLOSURE: Dr. Gernsheimer disclosed relevant relationships with Rigel Corporation, Principia, Sanofi, Vertex, Dova Pharmaceuticals, Cellphire, Novartis, and Amgen. Dr. Baumann Kreuziger reported no conflicts of interest.


1. Gernsheimer TB, Brown SP, Triulzi DJ, et al: Effects of tranexamic acid prophylaxis on bleeding outcomes in hematologic malignancy: The A-TREAT trial. 2020 ASH Annual Meeting & Exposition. Abstract 2. Presented December 6, 2020.

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Lisa Baumann Kreuziger, MD, MS, Associate Professor of Hematology/Oncology at Versiti/Medical College of Wisconsin, Milwaukee, introduced Terry B. Gernsheimer, MD, at the Plenary Session and spoke with The ASCO Post about the results of the study.