Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a "blood transfusion"-free hepatectomy. Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation. Prophylactic tranexamic acid in elective, primary coronary artery bypass surgery using cardiopulmonary bypass. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. Tranexamic acid and aprotinin reduce postoperative bleeding and transfusions during primary coronary revascularization. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. Comparison of the effects of aprotinin and tranexamic acid on blood loss and red blood cell transfusion requirements during the late stages of liver transplantation. Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo. Impact of tranexamic acid vs. aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: a prospective, randomised, double-blind trial.
To examine the feasibility of a real "blood transfusion"-free hepatectomy in a large group of patients with liver tumors.
                Bleeding control and blood transfusion remains problematic in liver resection. A real "blood transfusion"-free hepatectomy in a large group of patients has rarely been reported. The impact of tranexamic acid (TA), an antifibrinolytic agent, on blood transfusion in liver resection is unknown.
                A prospective double-blind randomized trial was performed on elective liver tumor resections. In group A, TA 500 mg was intravenously administered just before operation followed by 250 mg, every 6 hours, for 3 days. In group B, only placebo was given. The patients' background, blood transfusion rates, and early postoperative results in the 2 groups were compared. Factors that influenced blood requirement were analyzed.
                There were 108 hepatectomies in group A and 106 hepatectomies in group B. The patients' backgrounds, operative procedures, and hepatectomy extent did not significantly differ between the 2 groups. Although the differences of the operative morbidity and postoperative stay were not significant, a significantly lower amount of operative blood loss, lower blood transfusion rate, shorter operative time, and lower hospital costs were found in group A patients. No patient in group A received blood transfusion. No hospital mortality occurred in either group. Tumor size and use of TA were independent factors that influenced blood transfusion.
                Perioperative parenteral use of TA reduced the amount of operative blood loss and the need for blood transfusion in elective liver tumor resection. A real "blood transfusion"-free hepatectomy may be feasible with the assistance of parenteral TA. Tranexamic acid (TA) is a synthetic drug that inhibits fibrinolysis. It has been administered to decrease the use of blood products during cardiac surgery and orthotopic liver transplantation when infused in larger doses. A small-dose infusion of aprotinin causes a reduction in fibrinolysis and blood product requirement during orthotopic liver transplantation without apparent risk of intravascular thrombosis. This prospective study was designed to investigate whether a small-dose infusion of TA would be equally effective in reducing fibrinolysis and blood product transfusions during orthotopic liver transplantation. A double-blind, controlled study was undertaken to compare the efficacy of a small-dose TA infusion with that of a placebo. Thirty-two consecutive patients were randomized either to the TA group (n = 16), which received an intravenous infusion of 2 mg x kg(-1) x h(-1), or to the control group (n = 16), which received an identical volume of normal saline. Coagulation values were measured, a field rating was made by the surgeon, and a thromboelastogram was produced at four predetermined intervals throughout the case-before TA infusion was started, after portal vein ligation, 10 min after reperfusion, and at the end of surgery. Intraoperative transfusion requirements were recorded during the procedure and for the first 24 h postoperatively. A record was kept of any intraoperative epsilon-aminocaproic acid administered for uncontrolled fibrinolysis. The thromboelastogram clot lysis index was significant for lysis in the control group during both the anhepatic and the neohepatic phases (P < 0.01 and P < 0.05, respectively) when compared with the TA group. Fibrin degradation products were significantly increased (>20 microg/mL) in the control group at reperfusion (P < 0.03) and at the end of surgery (P < 0.01). D-dimers were also significantly increased (>1 mg/L) in the control group at the end of surgery (P < 0.04). Nine of the 16 control patients versus 3 of the 16 TA patients required epsilon-aminocaproic acid rescue for fibrinolysis. There were no other significant differences between groups. Transfusion requirements during surgery and for the first 24 h postoperatively did not differ significantly between the two groups. We conclude that the use of small-dose TA reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation. Perioperative use of tranexamic acid (TA), a synthetic antifibrinolytic drug, decreases perioperative blood loss, and the proportion of patients receiving blood transfusion in cardiac surgery, but the results may vary in different clinical settings. The primary objective of the present study was to determine the efficacy of TA to decrease chest tube drainage and the proportion of patients requiring perioperative allogeneic transfusions following primary, elective, on-pump coronary artery bypass grafting (CABG) in patients with a low baseline risk of postoperative bleeding.
                In a double-blinded, prospective, placebo-controlled study, 46 patients were randomized into two groups. One group received TA 1.5 g as a bolus, followed by a constant infusion of 200 mg/h until 1.5 g. The other group received placebo (0.9% saline). Among exclusion criteria were treatment with acetylsalicylic acid, non-steroidal anti-inflammatory drugs or other platelet inhibitors within 7 days before surgery.
                Preoperative demographics, biochemical and surgical characteristics were comparable between groups. At 6 h postoperatively, there was a trend towards a greater blood loss (median and interquartile range) in the placebo group (710 and 460-950 ml) compared to the TA group (400 and 350-550 ml), but the difference did not reach statistical significance. Neither were transfusion rates and the amount of autotransfused shed mediastinal blood different between the groups postoperatively. Postoperative d-dimer concentrations were significantly higher in the placebo group compared to the TA group (P < 0.001) This difference could not be explained by differences in the amount of autotransfused shed mediastinal blood alone. Plasma concentrations of beta-thromboglobulin and platelet factor 4 were significantly increased postoperatively in both groups, but without any intergroup differences. Seven patients (15%), one in the TA group and six in the placebo group, were reoperated due to excessive bleeding. Surgical correctable bleeding was found in all except two patients from the placebo group.
                An antifibrinolytic effect following prophylactic use of TA in elective, primary CABG among patients with a low risk of postoperative bleeding, did not result in any significant decrease in postoperative bleeding compared to a placebo group. Risks and costs of allogeneic blood transfusions mandate strategies to reduce blood loss in surgery. The objective of this study was to assess the efficacy of antifibrinolytic treatment in reducing perioperative blood loss during total knee replacement.
                A double-blind, randomized and placebo-controlled clinical trial was carried out on 127 patients undergoing total knee replacement. Patients in the study group received tranexamic acid 10 mg kg(-1) i.v. just before the tourniquet was deflated and 3 h later, or epsilon-aminocaproic acid 100 mg kg(-1) before tourniquet deflation followed by continuous perfusion (1 g h(-1)) during 3 h. External perioperative blood loss was measured and total blood loss was calculated. The number of patients transfused and number of packed red cell (PRC) units transfused was recorded and possible postoperative thromboembolic complications were investigated.
                Total blood loss [mean (sd)] was 1099 ml (535) in the group that received antifibrinolytic agents and 1784 ml (660) in the control group (P<0.001). Five patients (7.5%) in the study group and 23 (38.3%) in the control group (P<0.001) received blood transfusions; the first group received a mean of 0.10 PRC unit per patient and the second, 0.58 (P<0.001). Mean reduction in haemoglobin levels (g dl(-1)) between preoperative and fifth day postoperative readings was 2.5 (0.9) in the study group and 3.4 (1.2) in the control group (P<0.001). Clinical assessment did not reveal any thromboembolic complications.
                Antifibrinolytic agents produce a significant decrease in blood loss in patients undergoing total knee replacement, reflected in a reduction in the number of blood transfusions required. We evaluated the blood conservation effects of tranexamic acid (TA) or aprotinin administered before and during cardiopulmonary bypass (CPB) in a prospective, randomized, double-blind study of 150 adult patients undergoing primary coronary artery bypass grafting surgery. Patients received either TA (2 g) or large-dose aprotinin (7 million KIU). Thirty additional untreated patients otherwise managed in a similar fashion were included from a recently completed study for comparison of outcomes. Demographic, medical, surgical, laboratory, mediastinal chest tube drainage (MCTD), transfusion, and outcome data were collected. Allogeneic blood product administration was tightly controlled. The demographic, medical, and surgical characteristics did not significantly differ between the two therapy groups. The median postoperative MCTD loss in the TA group did not significantly differ from that in the aprotinin-treated group (708 vs 600 mL). The percentage of patients that received no allogeneic blood products was 25% for the TA group and 27% for the aprotinin group (P = not significant). The median number of allogeneic blood products administered to the TA group (0 U) did not significantly differ from that administered to the aprotinin group (0 U). The percentage of patients with excessive MCTD (>1000 mL/24 h) did not significantly differ between groups (19% and 17%, respectively). In comparison, the control group had a significantly greater (P < 0.05) median MCTD (1020 mL), median allogeneic blood product exposure (4.5 U), and incidence of excessive MCTD (66%) and transfusion therapy (66%). These data help to support the use of pharmacologic methods to improve clinically relevant indicators of blood conservation for primary CPB procedures. Furthermore, the data show that TA is equivalent to aprotinin for blood conservation in patients at risk of excessive post-CPB bleeding and transfusion therapy. Implications: In a randomized, blind trial, we evaluated the effects of tranexamic acid or aprotinin on blood conservation after primary cardiopulmonary bypass surgery. Both drugs were equally effective in reducing blood loss, the incidence of transfusion, and the amount of blood products transfused compared with placebon. Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis.
                Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay.
                Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation.
                High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements. During liver transplantation (LT), profound activation of the fibrinolytic system can contribute significantly to perioperative bleeding. Prophylactic administration of antifibrinolytic agents has been shown to reduce blood loss and the need for allogeneic transfusion in these conditions.
                This prospective randomized trial included 51 cirrhotic patients undergoing LT. Patients were randomly assigned to receive either 280 mg of aprotinin (AP) followed by 70 mg per hour or 40 mg per kg tranexamic acid (TA) followed by 40 mg per kg per hour, administered from the end of the anhepatic phase until 2 hours after reperfusion of the graft, and the effects on blood loss and red blood cell (RBC) transfusion requirements were compared. Transfusion policy was standardized in all patients. In addition, the biological effects of the two drugs, as assessed by coagulation and fibrinolytic markers obtained during surgery, were evaluated in a subgroup of patients from each treatment group and compared with an historical control group that did not receive antifibrinolytic drugs.
                There was no significant difference between the two groups in perioperative blood losses (AP, 6200 [4620-8735] mL; TA, 5945 [4495-8527] mL; median [range]) or in RBC transfusions requirements (AP, 9 [6.75-15.25] units; TA, 10 [6.5-13.5] units). Inhibition of fibrinolysis was observed with both drugs compared with the control group. Coagulation appeared to be activated more with AP, however, whereas fibrinolysis was inhibited more by TA.
                Blood losses and RBC transfusion requirements were comparable regardless of the drug administered. TA may be as valuable as AP for controlling fibrinolysis in LT. 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. Aprotinin (AP) reduces blood loss and transfusions after cardiopulmonary bypass (CPB), but may sensitise patients and is expensive. Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are controversial. The aim of our prospective, randomised, double-blind study was to compare the impact of AP vs. TA on drainage blood loss and transfusion requirements in patients undergoing first time CABG on CPB.
                One hundred and twenty adult patients were randomised to receive either high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood products were transfused in a standardised fashion. Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge.
                The data from 118 patients (TA: n = 58, AP: n = 60) who completed the study according to protocol were analysed. Blood loss at 24 h postoperation in TA patients was significantly higher (896 +/- 354 ml) as compared to AP patients (756 +/- 347 ml; p = 0.03). TA patients received 1.5 +/- 1.5 units of red blood cells (AP: 1.5 +/- 1.7, p = 1.0), 1.3 +/- 2.0 units of fresh frozen plasma (AP: 1.0 +/- 2.0, p = 0.38) and 0.5 +/- 1.4 units of platelets (AP: 0.2 +/- 0.7, p = 0.15). Clinical data, including perioperative myocardial infarction rate, acute renal failure, mechanical ventilation, hospital stay and mortality, were not significantly different between either group.
                Our data show a difference in blood loss between TA and high-dose AP. Although statistically significant, it has little clinical relevance, because perioperative transfusion requirements were similar for both groups. Thus, TA appears to be a cost-effective alternative to AP in primary CABG patients.
None of the interventions seem to decrease peri-operative morbidity or offer any long-term survival benefit. Aprotinin and tranexamic acid show promise in the reduction of blood transfusion requirements in liver resection surgery. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the high risk of bias. Further randomised clinical trials with low risk of bias and random errors assessing clinically important outcomes such as peri-operative mortality are necessary to assess any pharmacological interventions aimed at decreasing blood loss and blood transfusion requirements in liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.