Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. The use of tranexamic acid to reduce postoperative bleeding following cardiac surgery: a double-blind randomized trial. Prophylactic tranexamic acid decreases bleeding after cardiac operations.
Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.
                This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919.
                10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077).
                Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.
                UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
                Copyright 2010 Elsevier Ltd. All rights reserved. Bleeding during the first 24 hours following cardiac surgery using cardio-pulmonary bypass (CPB) is a serious complication. Attempts to modify the degree of postoperative bleeding with pharmacologic therapy have met with limited success. Tranexamic acid, a potent inhibitor of plasminogen, may decrease the amount of mediastinal bleeding following surgery utilizing CPB. We assigned 30 patients who were about to undergo cardiac surgery to a double-blind randomized trial. The treatment group received tranexamic acid, given intravenously as 10 mg/kg over 30 minutes, at the time of skin incision, followed by a 1 mg/kg/hr infusion for 12 hours. The control group received a placebo (saline) of equal volume. Measurements of shed mediastinal blood and transfused homologous blood were made at 6, 12, and 24 hours postoperatively. Mediastinal blood loss in the treatment and control groups was 382 mL versus 594 mL at 6 hours (P = 0.08), 502 mL versus 848 mL at 12 hours (P = 0.04), and 711 mL versus 1160 mL at 24 hours (P = 0.02). The mean transfusion volumes after 24 hours were 356 mL in the treatment group and 528 mL in the placebo group (P = NS). Prophylactic tranexamic acid infusion decreases mediastinal blood loss following cardiopulmonary assisted cardiac surgery. Thirty-eight patients undergoing a cardiac operation randomly received either tranexamic acid, a potent inhibitor of plasminogen, or placebo in an effort to determine whether prophylactic antifibrinolytic therapy reduces chest tube drainage. Twelve-hour blood loss was 750 +/- 314 (standard deviation) ml in the placebo group and 496 +/- 228 ml in the drug group (p = 0.0057). Fibrin split products were present more frequently in patients in the placebo group (17 of 20 compared with four of 18 in the drug group; p = 0.0002). Tranexamic acid markedly decreased plasminogen availability (112 +/- 104 units in the placebo group versus 36 +/- 18 units in the drug group, p = 0.0058). Plasma fibrinogen concentrations were similar in the placebo and drug groups. Patients in the placebo group received more fresh-frozen plasma and more mediastinal shed blood than those in the drug group. No coagulation-related complication occurred in the group receiving tranexamic acid. We conclude that prophylactic tranexamic acid can be administered safely to inhibit fibrinolysis during cardiac operations, decrease postoperative bleeding, and possibly decrease the frequency of blood product transfusion.
Tranexamic acid safely reduces mortality in bleeding trauma patients without increasing the risk of adverse events.  TXA should be given as early as possible and within three hours of injury, as treatment later than this is unlikely to be effective. Further trials are needed to determine the effects of TXA in patients with isolated traumatic brain injury.