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PubMed1999

Hemostatic effects of aprotinin, tranexamic acid and epsilon-aminocaproic acid in primary cardiac surgery.

BACKGROUND: The effects of epsilon-aminocaproic acid (EACA) and tranexamic acid (TA) on bleeding and allogeneic transfusions, and the cost of pharmacological and transfusional treatment were compared to aprotinin (AP). METHODS: We randomized 210 patients subjected to elective cardiac surgery. Of these, 68 patients received EACA (a bolus of 5 g, an infusion of 2 g/h, and 2.5 g in the priming), 72 patients received TA (a bolus of 1 g, an infusion of 400 mg/h, and 500 mg in the priming), and 70 patients received AP (a bolus of 280 mg, an infusion of 70 mg/h, and 280 mg in the priming). Postoperative blood loss and homologous transfusions were collected and the cost of pharmacological treatment and homologous transfusions were calculated. RESULTS: Bleeding but not allogeneic transfusions was significantly higher in the EACA group (467+/-234 versus TA, 311+/-231 versus AP, 283+/-233; p < 0.001). Costs of pharmacological and transfusional treatment were significantly lower in the TA group ($58.10+/-$105.10) versus the EACA group ($100.70+/-$158.60) versus the AP group ($432.60+/-$118.70) (p < 0.0001). CONCLUSIONS: Compared to AP, TA has the same effects on bleeding and transfusions, but with a significant reduction of costs. Patients treated with EACA showed a significantly higher postoperative bleeding with an increased trend of transfusion requirement.

Aminocaproic Acid↗

PubMedDate not supplied

Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo.

UNLABELLED: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Aminocaproic Acid↗

PubMed1986

The inhibitory effect of tranexamic acid on human ovarian carcinoma cell grown in vitro and in vivo.

Effects of tranexamic acid on tumor growth were examined by using five kinds of human cultured cell lines derived from ovarian malignant tissues. An optimum inhibitory effect on cell proliferation was observed at a concentration of 10 mg/ml tranexamic acid, while replication of a clear cell carcinoma cell line (OK) was not inhibited by any concentration of tranexamic acid used in the present study. Exposure of a cystadenocarcinoma cell line (HR) to 10 mg/ml tranexamic acid for 2 hr resulted in significant growth retardation of tumors formed in nude mice. Further, tranexamic acid seemed to change the morphology of the ovarian carcinoma cells to enlarged cells with abundant cytoplasm. These results suggest that fibrinolytic factors are associated with growth of the tumor and tranexamic acid is useful as an adjuvant therapy for ovarian carcinoma.

Adenocarcinoma↗

PubMed1993

Prevention of postbypass bleeding with tranexamic acid and epsilon-aminocaproic acid.

In this institution, two antifibrinolytic agents have been in routine use before cardiopulmonary bypass (CPB) to prevent bleeding due to fibrinolysis; epsilon-aminocaproic acid (EACA) or tranexamic acid (TA) are administered as intravenous infusions over 2 hours, from the time of anesthetic induction until the onset of CPB. TA is 10 times more potent and binds more strongly to plasminogen than EACA. Data were collected retrospectively on 411 patients undergoing first-time coronary artery bypass grafting with cardiopulmonary bypass who had received one of four therapy regimens: 10 g of EACA (65 patients), 15 g of EACA (60 patients), 6 g of TA (100 patients), or 10 g of TA (75 patients). Patients who did not receive any drug (91) served as controls. Anesthetic technique and the heparin/protamine protocol did not differ. Blood collected by mediastinal and pleural tubes was autotransfused up to 6 hours postoperatively. Both TA and EACA reduced post-CPB bleeding in the first 24 hours. Ten grams of TA was the most effective, resulting in a 52% and 36% reduction in blood loss over controls at 6 and 24 hours, respectively. Although 10 g of TA was more effective than 6 g of TA in blood loss control for the first 6 hours, the difference was not significant at 24 hours. A significantly lower number of patients in the 10 g TA group received blood products than in control (28% v 49%) patients (P = 0.02). Pretreatment with 10 g of TA prevented excessive (over 750 mL in 6 hours) bleeding after CPB.

Aminocaproic Acid↗

PubMed1991

Effect of tranexamic acid on platelet ADP during extracorporeal circulation.

Seventeen adults received the antifibrinolytic drug tranexamic acid during cardiac surgery utilizing extracorporeal circulation (ECC). In 8 patients, drug administration began prior to skin incision (pre-ECC); infusions commenced after ECC and protamine administration in another 9 patients (post-ECC). Compared with the post-ECC group, the pre-ECC group exhibited less bleeding via mediastinal drains (420 vs. 655 mL/12 h median, P = 0.024), decreased frequency of the presence (greater than or equal to 10 micrograms/mL) of fibrin split products (P less than 0.05), and greater platelet dense granule content of adenosine diphosphate after surgery (15.47 vs. 4.05 nmoles/mg protein median, P = 0.021). Follow-up in vitro study of tranexamic acid inhibition of plasmin-induced platelet activation utilizing normal human platelet rich plasma and porcine plasmin revealed a 13-fold lower concentration of tranexamic acid for 50% inhibition when plasmin was preincubated with the drug (1.2 micrograms/mL, 95% CI = 1.13-1.60 micrograms/mL) compared to when platelet rich plasma was preincubated with the drug (16 micrograms/mL, 95% CI = 7.3-99. micrograms/mL). Plasmin inactivated with tranexamic acid retained its ability to inhibit thrombin-induced platelet activation, thus suggesting that tranexamic acid inhibits plasmin's catalytic activity and not its binding to platelets. Both clot lysis and platelet dysfunction may contribute to bleeding after ECC. Tranexamic acid blocks plasmin-induced partial platelet activation during ECC, thus preserving platelet function and promoting hemostasis after ECC.

Adenosine Diphosphate↗

PubMed2003

Tranexamic acid reduces blood loss after cementless total hip arthroplasty-prospective randomized study in 40 cases.

We investigated the effects of tranexamic acid in 40 patients who had received cementless total hip arthroplasty (THA) in a prospective, randomized study. In 20 patients, 1000 mg of whole-body tranexamic acid was administered intravenously 5 min before the operation started. The other 20 patients served as a control group and were operated on without tranexamic acid. Perioperative blood loss was similar in the tranexamic acid group and in the control group. Postoperative blood loss of the tranexamic acid group was significantly less than that of the control group at 2, 4, 6, 8, 10, and 12 h. Regarding time-related changes of postoperative blood loss, significant reduction was observed during the first 2 h after surgery in the tranexamic acid group ( P<0.001). After the first 2 h, there was no significant difference between the tranexamic acid group and the control group. Preoperative administration of tranexamic acid decreased postoperative blood loss until 12 h and total bleeding in cementless THA by reduction of blood loss during the first 2 h after surgery.

Antifibrinolytic Agents↗

PubMed2005

Biodegradable derivatives of tranexamic acid as transdermal permeation enhancers.

The purpose of this work was to develop a novel approach to transdermal permeation enhancer design, based on utilizing some favorable properties of their metabolites. As an example of this concept, a series of carbamic acid salts of tranexamic acid (TXA) esters was synthesized, because TXA was previously shown to improve skin barrier homeostasis. Enhancement activities of 1% TXA derivatives dispersed in both hydrophilic and lipophilic vehicles were evaluated in vitro using human skin and theophylline as a model drug. Dispersed in an aqueous donor vehicle, the dodecyl ester showed the enhancement ratio (ER) of 4.3+/-0.9, which is almost 2 times higher than that of 1-dodecylazepan-2-one (Azone; 2.2+/-0.7). From an isopropyl-myristate suspension, the decyl ester was the most effective enhancer (4.9+/-1.4), while Azone was inactive. Decomposition of the carbamate in a slightly acidic environment was shown by FTIR; hydrolysis of the pertinent ester by porcine esterase was monitored by TLC and HPLC. Biodegradable enhancers of this type could mediate easier and faster recovery of the skin barrier after transdermal delivery through the action of the released TXA.

Administration, Cutaneous↗

PubMed2000

Preservation of collagen-induced whole blood platelet aggregation by tranexamic acid therapy in primary cardiac valve surgery.

Haemostatic disorder is one of the most common complications following cardiac surgery with cardiopulmonary bypass (CPB). Tranexamic acid reduces blood loss and allogeneic blood transfusion requirement in cardiac surgery. It had been thought that tranexamic acid inhibited fibrinolysis alone following CPB. In the present study, the haemostatic effects of tranexamic acid (20 mg/kg body weight bolus after induction of anaesthesia followed by continuous infusion at 2 mg/kg/h), including fibrinolysis and platelet function, were investigated in 22 patients (tranexamic acid group n = 12; control group n = 10) undergoing primary cardiac valve surgery. Fibrinolysis following CPB was reduced significantly in the tranexamic acid group. Following protamine administration, the reduction of collagen-induced whole blood platelet aggregation was mitigated significantly in the tranexamic acid group compared with the control group (36% reduction in the tranexamic acid group vs 58% in the control group; p = 0.011), although platelet counts did not differ between the two groups. In conclusion, tranexamic acid not only inhibits fibrinolysis directly, but also may preserve platelet function following CPB.

Adult↗

PubMed1999

Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty.

We have investigated the effect of treatment with tranexamic acid, an inhibitor of fibrinolysis, on blood loss, blood transfusion requirements and blood coagulation in a randomized, double-blind, placebo-controlled study of 42 patients after total knee arthroplasty. Tranexamic acid 15 mg kg-1 (n = 21) or an equivalent volume of normal saline (n = 21) was given 30 min before surgery and subsequently every 8 h for 3 days. Coagulation and fibrinolysis values, blood loss and blood units administered were measured before administration of tranexamic acid, 8 h after the end of surgery and at 24 and 72 h after operation. Coagulation profile was examined (bleeding time, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), plasminogen, beta-thromboglobulin and fibrinogen). Fibrinolysis was evaluated by measurement of concentrations of D-dimer and fibrinogen degradation products (FDP). Total blood loss in the tranexamic acid group was 678 (SD 352) ml compared with 1419 (607) ml in the control group (P < 0.001), and occurred primarily during the first 24 h after surgery. Thirteen patients received 1-5 u. of packed red blood cells in the control group compared with two patients in the tranexamic acid group, who received 3 u. (P < 0.001). Postoperative packed cell volume values were higher in the tranexamic acid group despite fewer blood transfusions. Postoperative concentrations of plasminogen were decreased significantly in the tranexamic acid group (P < 0.001). Platelet count, PT, aPTT, bleeding time, beta-thromboglobulin, fibrinogen and FDP concentrations did not differ between groups, but D-dimer concentrations were increased in the control group. Thromboembolic complications occurred in two patients in the control group compared with none in the tranexamic acid group.

Aged↗

PubMed1986

Adjuvant effects of tranexamic acid to chemotherapy in ovarian cancer patients with large amount of ascites.

Eleven patients with advanced ovarian carcinoma who had large quantities of ascites during the course of previous chemotherapy were tested with intraperitoneal injections of tranexamic acid, followed by combination chemotherapy. A 4-g dose of tranexamic acid was administered intraperitoneally every day for at least 2 weeks. Seven out of 11 patients (63.6%) showed changes from positive to negative in Papanicolaou smears of the ascitic fluid after treatment with tranexamic acid. A marked reduction of ascitic fluids was observed in 4 of 11 patients (36.4%). If 2 cases with partial reduction of ascites are included, the response rate improved to 54.5%. Median survival time after initiation of treatment with tranexamic acid was significantly longer in patients with good response to tranexamic acid than in patients with poor response. Proliferation of cells in cultures established from ovarian cancer tissue of a patient with good response to tranexamic acid was inhibited at all concentrations of tranexamic acid used in this study, in contrast to non-inhibition of similar cells cultured from a patient with poor response, at any concentration of tranexamic acid. These results suggest that treatment with tranexamic acid suppresses malignant cells in the ascites, followed by reduction of ascites themselves, and an improvement in the response rate to subsequent chemotherapy.

Adult↗

PubMed2000

Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model.

OBJECTIVES: Tranexamic acid (t-AMCA) has been shown to cause severe convulsions in humans and cats when applied topically to the central nervous system. We wanted to determine whether pure t-AMCA or fibrin sealant (FS) containing t-AMCA would induce similar effects when applied to the spinal cord in a rat model. METHODS: Following low-thoracic laminectomy, the dura was incised to expose the dorsal surface of the lumbar enlargement. Rats were allocated to one of the following treatments: 1) t-AMCA (10 mg/ml), 2) vehicle (phosphate buffered saline), 3) FS containing t-AMCA, 4) FS containing aprotinin. The response of the rats was evaluated based on neurological and behavioral observations. Additionally, motor function was scored in the rats that had received FS. RESULTS: Application of either 10 mg/ml t-AMCA or FS containing t-AMCA caused severe hind limb spasms that developed into spontaneous generalized convulsions. Two of the three rats that had received FS containing t-AMCA died of respiratory failure. In contrast, application of vehicle or FS containing aprotinin did not cause any abnormal conditions of the animals. CONCLUSION: Tranexamic acid may cause severe complications when used in the central nervous system. Thus, fibrin sealants containing t-AMCA should not be used in neurosurgery.

Animals↗

PubMed1989

Enhancement of the activation of Glu-plasminogen by urokinase in the simultaneous presence of tranexamic acid or fibrin.

The activation rate of Glu-plasminogen (Glu-plg) by urokinase (UK) was enhanced in the presence of either tranexamic acid or fibrin with an increase in the catalytic rate constant (kcat). The maximum increase in kcat was obtained at 0.5 mM of tranexamic acid and 0.1 microM of fibrin. Km did not change. The addition of fibrin to 1 mM tranexamic acid resulted in a further increase in kcat of the UK activation of Glu-plg. On the other hand, the addition of tranexamic acid to 0.1 microM fibrin further increased kcat of the UK activation of Glu-plg. Thus, stimulatory effects were observed on the activation of Glu-plg by UK in the simultaneous presence of tranexamic acid and fibrin. Fibrin-binding sites on the kringle 5 of Glu-plg may be involved in the further increase in the activation rate of Glu-plg by UK in the presence of both fibrin and tranexamic acid in comparison to that in the presence of tranexamic acid alone. Possibly, the Glu-plg binding with both tranexamic acid and fibrin (at kringle 5) may be most effectively activated by UK. It is also suggested that two molecules of Glu-plg bind to one molecule of fibrin monomer.

Cyclohexanecarboxylic Acids↗

PubMed2004

Dose comparison of tranexamic acid in pediatric cardiac surgery.

To compare different doses of tranexamic acid, 150 consecutive children with congenital cyanotic heart disease were randomly assigned to one of 5 groups of 30 each. Group A served as a control. Group B received 50 mg.kg(-1) of tranexamic acid at induction of anesthesia. Group C received 10 mg.kg(-1) at induction followed by an infusion of 1 mg.kg(-1).h(-1). Group D had 10 mg.kg(-1) at induction, 10 mg.kg(-1) on bypass, and 10 mg.kg(-1) after protamine. Group E had 20 mg.kg(-1) at induction and again after protamine. The control group had the longest sternal closure time, the greatest blood loss in the first 24 hours, and the highest requirements for blood and blood products. Among the 4 groups given tranexamic acid, group D (triple dose) had the best results, followed by group E (double dose). Group B (single dose) had the worst results among the groups receiving tranexamic acid.

Adolescent↗

PubMed1987

Distribution of tranexamic acid to plasma and saliva after oral administration and mouth rinsing: a pharmacokinetic study.

The objective of the study was to investigate the content of tranexamic acid in plasma and in mixed, unstimulated whole saliva after oral administration and mouth rinsing. Ten healthy volunteers each received 1 g of tranexamic acid orally, whereas 20 healthy volunteers rinsed their mouths with 10 mL of a 5% aqueous tranexamic acid solution for two minutes. Blood and saliva were collected 30, 60, 120, 240, 360, and 480 minutes after administration of tranexamic acid. Samples of blood and saliva were analyzed for tranexamic acid content by electron capture gas chromatography. After oral administration, the mean plasma concentration of tranexamic acid reached its maximum after 120 minutes at approximately 7 micrograms/mL, whereas none of the saliva samples contained tranexamic acid at detectable levels. After mouth rinse, the plasma concentrations remained below 2 micrograms/mL, whereas the concentrations found in saliva initially were very high (after 30 minutes mean concentration above 200 micrograms/mL) and remained at a therapeutic level for more than two hours. These findings indicate, that fibrinolysis in the oral cavity can be inhibited only by local administration of tranexamic acid. This finding may be of significance when the drug is used for prevention and treatment of bleeding in the oral cavity in patients with coagulation defects.

Administration, Oral↗

PubMed1987

Tranexamic acid in acute upper gastrointestinal bleeding.

The effect of the antifibrinolytic substance, tranexamic acid, has been studied in 5 double-blind, randomized, placebo-controlled trials in patients with acute upper gastrointestinal bleeding. The results of these trials have varied with regard to blood transfusion requirements and the frequency of operations. All of the studies have shown lower mortality in patients treated with tranexamic acid. Thus tranexamic acid would seem to be indicated in acute upper gastrointestinal bleeding.

Blood Transfusion↗

PubMed1983

Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding.

We studied the effects of tranexamic acid (an antifibrinolytic agent) and cimetidine on acute upper-gastrointestinal-tract bleeding in a double-blind randomized placebo-controlled trial in 775 patients with hematemesis or melena or both. Mortality was significantly reduced in patients receiving either tranexamic acid (mortality, 6.3 per cent) or cimetidine (7.7 per cent), as compared with patients receiving placebo (13.5 per cent) (P = 0.0092 for tranexamic acid vs. placebo, P = 0.045 for cimetidine vs. placebo). Ninety-nine patients were withdrawn before the code was broken, mainly because their primary illness was considered not to be due to acute upper-gastrointestinal-tract bleeding. Mortality among those withdrawn was high (22 per cent), and their exclusion reduced death rates to 4 per cent in those given tranexamic acid, 8 per cent in those given cimetidine, and 11 per cent in those given placebo (P = 0.0072 for tranexamic acid vs. placebo, P greater than 0.50 for cimetidine vs. placebo). The reduced mortality associated with tranexamic acid was detectable at both participating hospitals and in most of the main subgroups of patients classified according to site of bleeding. However, treatment with this agent was not associated with any decrease in the rate of rebleeding or the need for operation.

Acute Disease↗

PubMed1997

The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery.

The antifibrinolytic drug, tranexamic acid, decreases blood loss in adult patients undergoing cardiac surgery. However, its efficacy has not been extensively studied in children. Using a prospective, randomized, double-blind study design, we examined 41 children undergoing repeat sternotomy for repair of congenital heart defects. After induction of anesthesia and prior to skin incision, patients received either tranexamic acid (100 mg/kg, followed by 10 mg.kg-1.h-1) or saline placebo. At the onset of cardiopulmonary bypass, a second bolus of tranexamic acid (100 mg/kg) or placebo was administered. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. Children who were treated with tranexamic acid had 24% less total blood loss (26 +/- 7 vs 34 +/- 17 mL/kg) compared with children who received placebo (univariate analysis P = 0.03 and multivariate analysis P < 0.01). Additionally, the total transfusion requirements, total donor unit exposure, and financial cost of blood components were less in the tranexamic acid group. In conclusion, tranexamic acid can reduce perioperative blood loss in children undergoing repeat cardiac surgery.

Antifibrinolytic Agents↗

PubMed2003

The use of tranexamic acid to reduce blood loss during total knee arthroplasty.

HYPOTHESIS: The fall in haemoglobin following unilateral total knee arthroplasty is reduced by tranexamic acid administration. METHODS: 60 patients were studied in total, 30 received tranexamic acid 10 mg/kg on induction and a further dose shortly before the release of the tourniquet. Surgery was performed by the senior author in a standardised fashion using the Freeman Samuelson cemented total knee replacement. Haemoglobin levels were measured 2 weeks pre and 3 days post operatively. Any complications were noted. A control group was matched using the Bone and Joint Research Unit database for age, sex, disease and pre-operative haemoglobin level. This group had been monitored in the same way as the group treated with tranexamic acid. RESULTS: In the group receiving no tranexamic acid the mean fall in haemoglobin was 2.8 g/dl (95% CI of mean 2.5-3.2) and in the group treated with tranexamic acid 1.7 g/dl (95% CI of mean 1.3-2) P<0.01. There were no complications in either group. CONCLUSIONS: The administration of tranexamic acid is an effective method of reducing the haemoglobin fall following knee arthroplasty.

Aged↗