Clot Stabilizer Does Not Prevent Bleeding in Hematologic Malignancies

blood clot: blood clotThe clot stabilizer tranexamic acid does not prevent bleeding in patients with hematologic malignancies who receive routine prophylactic platelet transfusions, according to researchers at the 2020 ASH Annual Meeting (Abstract 2). Severe thrombocytopenia of grade 2 or higher occurs in up to 70 percent of patients undergoing treatment for hematologic malignancy, despite optimal prophylactic platelet transfusion therapy. Antifibrinolytic therapy has been shown to reduce bleeding and transfusion needs in patients with inherited bleeding disorders and in multiple surgical settings, but evidence is lacking in therapy-induced thrombocytopenia in hematologic malignancy. “Clearly, patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery,” said senior author Terry B. Gernsheimer, MD, Professor of Hematology at the University of Washington School of Medicine. “Their bleeding likely is due to endothelial damage—damage to the lining of blood vessels—that tranexamic acid would not treat. To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-versus-host disease in patients receiving a transplant.” Although not life-threatening, grade 2 bleeding—for example, a nosebleed lasting more than 30 minutes—can be concerning. Bleeding of grade 3 or 4 can be life-threatening and warrant blood transfusions. Most patients undergoing treatment for blood cancers are routinely given platelet transfusions to prevent bleeding, but many continue to experience bleeding episodes, she said. Tranexamic acid works by slowing the process by which blood clots naturally break down. Study Results Abstract 2 During the conference, Gernsheimer presented the results of the American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia trial (The A-TREAT Trial). This multicenter, double-blind, placebo-controlled randomized clinical trial recruited patients from three U.S. medical centers to evaluate the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements in patients undergoing treatment for hematologic malignancy. The trial evaluated 327 patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation. They were anticipated to have hypoproliferative thrombocytopenia. Patients received either tranexamic acid intravenously 1,000 mg or saline—or oral drug 1,300 mg or placebo—every 8 hours beginning when the platelet count was ≤30,000/μL and continuing until a platelet count recovery of >30,000/μL or if a diagnosis of thrombosis was made. Patients were transfused prophylactically for counts of ≤10,000/μL or if indicated in the judgment of the treating physician. Daily assessments for bleeding were made by trained research staff for inpatients or by self-assessment in a patient diary for outpatients, and by patient interview and chart review. The results revealed no significant differences among the study groups in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions patients required during the treatment period and for up to 14 days afterward. Patients receiving tranexamic acid had a significantly higher rate of occlusions in their central venous line that required clearing with a clot-dissolving drug, but there was no difference in the occurrence of clots in patients' veins or arteries. Recurrent line occlusion led to permanent discontinuation of drug in 4.9 percent of tranexamic acid and 1.8 percent of placebo subjects. No increase in any other non-catheter thrombotic events was noted. No patient died from a thrombotic event in 120 days following activation of tranexamic acid. There were no deaths due to bleeding. Researchers cautioned that the study's focus is different from other situations in which tranexamic acid has been found effective, such as to treat bleeding related to childbirth, surgery, or inherited blood disorders. “Prophylactic tranexamic acid has no effect on the incidence of WHO grade 2 or higher bleeding when given in addition to routine platelet transfusions to severely thrombocytopenic patients undergoing therapy for hematologic malignancy,” Gernsheimer said. “An increased incidence of line occlusion in the tranexamic acid arm was observed, but no increase in other types of thrombotic events was detected.” He noted that other studies could help elucidate whether the drug may be helpful for specific subgroups of patients with blood cancers or as a treatment for bleeding, rather than as a preventive measure in these patients. It may also be useful to prevent or treat bleeding in patients with other causes of low platelet counts. Mark L. Fuerst is a contributing writer.