TXA Prophylaxis No Help for Bleeding in Blood Cancers


Prophylactic antifibrinolytic therapy with tranexamic acid (TXA) failed to reduce bleeding during treatment for hematologic malignancies, a first-of-its-kind randomized trial showed.

The incidence of grade 2+ bleeding decreased from 48.8% with transfusion plus placebo to 45.4% with TXA in addition to transfusion, a difference that failed to achieve statistical significance. Stratification of patients by allogeneic and autologous transplantation, and by use of chemotherapy, did not identify patients who benefited from the addition of TXA.

Secondary, exploratory, and post hoc analyses also failed to demonstrate a beneficial effect of TXA, reported Terry B. Gernsheimer, MD, of the University of Washington in Seattle, during the American Society of Hematology (ASH) virtual meeting.

“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,” Gernsheimer stated. “Additionally, platelet and red blood cell transfusions did not differ between the arms, and an increased incidence of central line occlusion in the tranexamic acid arm was observed, but there was no difference in other thrombotic events or mortality.”

“This study looked only at tranexamic acid as an adjunct to routine prophylactic platelet transfusion in preventing bleeding,” she noted. “We cannot rule out the usefulness of tranexamic acid in other settings of thrombocytopenia, such as the treatment of active bleeding, refractoriness to platelet transfusion, or prophylaxis for procedures.”

Despite fairly common use as an adjunct to platelet transfusion, prophylactic TXA had not been evaluated in a phase III trial to prove its safety and efficacy, Gernsheimer, and Lisa Hicks, MD, of the University of Toronto, pointed out during an ASH press briefing.

“The results suggest that tranexamic acid should not be routinely used as prophylaxis in non-bleeding patients with low platelet counts and blood cancer,” said Hicks, the press briefing moderator.

Gernsheimer presented primary results from the multicenter American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT). The trial had its origin in the recognition that “best practice” transfusion therapy fails to prevent many episodes of bleeding in hematologic malignancies. Rates of grade 2+ bleeding have been reported in as many as 78% of patients undergoing allogeneic transplantation, said Gernsheimer. Investigators hypothesized that rates of bleeding could be reduced by prophylactic inhibition of fibrinolysis.

“Although not uncommonly used in this setting, there was a lack of evidence that it is efficacious,” she said.

A-TREAT involved patients undergoing treatment (transplantation or chemotherapy) for various hematologic malignancies. Eligible patients were expected to have a platelet count ≤10,000/uL for 5 days or longer. Patients were randomized to TXA or placebo, and treatment began whenever a patient’s platelet count fell below 30,000/uL. Assigned treatment was discontinued after 30 days or platelet recovery; thrombosis, veno-occlusive disease (VOD), or recurrent central line occlusions; visible hematuria; physician or patient request; or initiation of open-label TXA.

The trial did not have a prescribed threshold for red cell transfusion, but standard practice at participating centers was to begin transfusion at a hemoglobin of about 8.5 g/dL and platelet transfusion at a count ≤10,000/uL, said Gernsheimer. The primary endpoint was incidence of grade 2+ bleeding by WHO criteria (observable organ system bleeding requiring minor intervention).

The study population had a median age of 54, and men accounted for 58% of patients. Treatment category consisted of 39% allogeneic transplantation, 22% autologous transplantation, and 39% chemotherapy and/or immunotherapy.

Primary data analysis included 330 randomized patients. Time on study drug averaged 12 days. The results showed that TXA was associated with a 14% reduction in the odds ratio (OR) for grade 2+ bleeding, which did not achieve statistical significance (95% CI 0.52-1.38). Analysis by therapeutic group yielded ORs of 0.71 to 0.94, none of which reached statistical significance. Analyses focusing on days without bleeding, platelet and red cell transfusions, and grade 3+ bleeding also did not yield any significant differences.

Patients assigned to TXA had a significantly higher rate of thrombotic events (19.5% vs 11.0%, P<0.05). Central line occlusions drove the overall difference (16.5% with TXA vs 6.7% with placebo). Thrombotic events through 120 days (0.2% overall), VOD within 30 days of last dose (1.5%), all-cause mortality at 30 days (2.7%) or 120 days (11.5%), or thrombosis-associated mortality at 120 days (0%) did not differ between treatment groups.

Last Updated December 05, 2020

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow


The study was supported by the University of Washington and the National Heart, Lung and Blood Institute.

Gernsheimer disclosed relevant relationships with Rigel Corporation, Principia, Sanofi, Vertex, Dova Pharmaceuticals, Cellphire, Novartis, and Amgen.

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