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 in subarachnoid hemorrhage. A double-blind study. Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo. Reduction of blood loss and transfusion requirements after coronary artery bypass grafting: similar efficacy of tranexamic acid and aprotinin in aspirin-treated patients. The effect of tranexamic acid on reducing blood loss in cementless total hip arthroplasty under epidural anesthesia. Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial. Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery.
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. The effects of intravenous tranexamic acid were compared with placebo in 64 patients with subarachnoid hemorrhage. A double-blind procedure was used. One gram of tranexamic acid was given intravenously every 4 hours up to the time of operation on an intracranial arterial aneurysm or for up to 21 days after the first bleeding if operative treatment was not feasible. There were no differences in re-bleeds, morbidity or mortality between the tranexamic and placebo-treated groups. No thromboembolic complications were noted in either group. Our results do not support the use of tranexamic acid in subarachnoid hemorrhage in daily doses of 6 g. Perioperative bleeding following coronary artery bypass grafting (CABG) is associated with increased blood product usage. Although aprotonin is effective in reducing perioperative blood loss, excessive cost prohibits routine utilization. Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive antifibrinolytic agents, which, when given prophylactically, may reduce blood loss. The present study was undertaken to compare the efficacy of TA and EACA in reducing perioperative blood loss.
                The study population consisted of first-time CABG patients. Patients were allocated in a prospective double-blind fashion: (1) group EACA (loading dose 15 mg/kg, continuous infusion 10 mg/kg per hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of normal saline for 6 hours, N = 19).
                Treatment groups were similar preoperatively. No significant difference in intraoperative blood loss or perioperative use of blood products was noted. D-dimer concentration was elevated in the control group compared to the EACA and TA groups (p < 0.05). Group TA had less postoperative blood loss than the EACA and control groups at 6 and 12 hours postoperatively (p < 0.05). TA had reduced total blood loss (600 +/- 49 mL) postoperatively compared to EACA (961 +/- 148 mL) and control (1060 +/- 127 mL, p < 0.05).
                TA and EACA effectively inhibited fibrinolytic activity intraoperatively and throughout the first 24 hours postoperatively. TA was more effective in reducing blood loss postoperatively following CABG. This suggests that TA may be beneficial as an effective and inexpensive antifibrinolytic in first-time CABG patients. In patients with coronary artery disease, continuation of aspirin may reduce the incidence of unstable angina and preoperative myocardial infarction before surgery, but the risk of perioperative bleeding may be increased.
                The efficacy of aprotinin and tranexamic acid (TXA) was examined in a prospective, randomized, double-blind trial involving 56 patients scheduled for coronary artery bypass grafting and who received aspirin 100 mg/day until the day of the operation. Group I received high-dose aprotinin whereas group II received 10 g of tranexamic acid (TXA) over 20 minutes before sternotomy. Heparinization during cardiopulmonary bypass was controlled with HDTT (high-dose thrombin time) to eliminate interference of aprotinin on ACT (celite activated clotting time). Postoperative blood loss and transfusion requirements were registered during the first 24 hours.
                The demographics, coagulation, and intraoperative parameters were similar in both groups. Postoperative blood loss (aprotinin 840 mL /24 hours, TXA 880 mL/24 hours, p = 0.481), and transfusion requirements (2.18 units/patient in the aprotinin group, 2.11 units/patient in the TXA group) were not remarkably different between the two regimen protocols. No perioperative myocardial infarction, pulmonary embolism, cerebrovascular event, or other thrombotic events were observed.
                In this trial, we were not able to demonstrate any difference in postoperative bleeding in patients pretreated with aspirin after high-dose aprotinin or TXA. From a practical point of view, TXA is safe, less expensive than aprotinin, and easy to handle, and can be recommended in patients pretreated with aspirin to improve postoperative hemostasis. Total hip arthroplasty (THA) is associated with high intraoperative and postoperative blood loss. Antifibrinolytic drugs have been used to minimize the potential risks of bleeding and blood transfusion. Studies on the effect of tranexamic acid on decreasing blood loss in THA have revealed interesting results, but most have focused on cemented THA. Yet its benefits in THA, especially in cementless THA, have not been proved. We conducted a prospective double-blind randomized controlled study on 64 patients who were candidates for cementless THA under epidural anesthesia between 2006 and 2008. Patients were randomly assigned into study and control groups. Patients in both groups were well matched regarding preoperative characteristics. Five minutes preoperatively 32 patients of the study and control groups received 15 mg/kg tranexamic acid or normal saline intravenously respectively. Our findings showed a significantly smaller decrease in 6- and 24-hour postoperative hemoglobin levels, less intraoperative and postoperative bleeding, and less need for allogenic blood transfusion in the tranexamic acid group. Our results also revealed a higher mean of 6- and 24-hour hematocrit level and shorter hospital stay in the tranexamic acid group compared to the control group, which were not statistically meaningful. In our study no thromboembolic event was seen; except 1 patient in the control group. Our study showed that administering tranexamic acid before the start of cementless THA under epidural anesthesia can reduce intraoperative and postoperative bleeding as well as need for blood transfusion.
                Copyright 2010, SLACK Incorporated. This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding. Tranexamic acid reduces postoperative bleeding after coronary artery bypass grafting. We evaluated the effects of a single dose of tranexamic acid given immediately before cardiopulmonary bypass (CPB) in patients treated with aspirin until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. Eighty patients were included and divided into two groups: one group received tranexamic acid 30 mg/kg, and one group received placebo (0.9% NaCl) as a bolus injection before CPB. Postoperative blood loss was recorded for 16 h. Transfusions of blood products were recorded for the whole hospital stay. Transfusions of packed red cells were given when the hematocrit value was less than 20% during CPB and less than 25% after surgery. The patients in the tranexamic acid group had significantly less postoperative bleeding compared with the patients in the placebo group (mean [SD]) (475 [274] mL versus 713 [243] mL; P < 0.001). An effective inhibition of fibrinolysis was found in patients receiving tranexamic acid. Tranexamic acid reduces postoperative bleeding in coronary artery bypass grafting patients treated with aspirin until the day before surgery.
                Continuation of aspirin medication until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of a single dose of tranexamic acid (30 mg/kg) immediately before cardiopulmonary bypass significantly reduced postoperative bleeding and inhibited fibrinolysis in these patients.
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.