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The optimal dose of tranexamic acid (TA) is still an issue. The authors compared two doses of TA during cardiac surgery in a multicenter, double-blinded, randomized study.Patients were stratified according to transfusion risk, then randomized to two TA doses: 10 mg/kg bolus followed by 1 mg·kg−1·h−1 infusion (low dose) until the end of surgery or 30 mg/kg bolus followed by 16 mg·kg−1·h−1 infusion (high dose). The primary endpoint was the incidence of blood product transfusion up to day 7. Secondary ones were incidences of transfusion for each type of blood product and amounts transfused, blood loss, repeat surgery, TA-related adverse events, and mortality.The low-dose group comprised 284 patients and the high-dose one 285. The primary endpoint was not significantly different between TA doses (63% for low dose vs. 60% for high dose; P = 0.3). With the high dose, a lower incidence of frozen plasma (18 vs. 26%; P = 0.03) and platelet concentrate (15 vs. 23%; P = 0.02) transfusions, lower amounts of blood products (2.5 ± 0.38 vs. 4.1 ± 0.39; P = 0.02), fresh frozen plasma (0.49 ± 0.14 vs.1.07 ± 0.14; P = 0.02), and platelet concentrates transfused (0.50 ± 0.15 vs. 1.13 ± 0.15; P = 0.02), lower blood loss (590 ± 50.4 vs. 820 ± 50.7; P = 0.01), and less repeat surgery (2.5 vs. 6%; P = 0.01) were observed. These results are more marked in patients with a high risk for transfusion.A high dose of TA does not reduce incidence of blood product transfusion up to day 7, but is more effective than a low dose to decrease transfusion needs, blood loss, and repeat surgery.