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Effect of tranexamic acid on early postvitrectomy diabetic haemorrhage; a randomised clinical trial.

AIMS: To evaluate the effect of tranexamic acid on early postvitrectomy haemorrhage in diabetic patients. METHODS: In a clinical trial, 62 diabetic patients scheduled for vitrectomy were randomly assigned to two groups. The treatment group (32 eyes) received two doses of tranexamic acid (10 mg/kg) shortly before and after the operation intravenously, continued orally for 4 days (20 mg/kg/8 hours). The control group (30 eyes) received no medication. Both media clarity and visual acuity were compared during 4 weeks. RESULTS: Four weeks after surgery visual acuity was low (< or =1 metre counting fingers) in 21.4%, moderate (>1 metre counting fingers but<20/200) in 14.3%, and good (> or =20/200) in 64.3% of the treated group. Corresponding figures in the control group were 26.1%, 26.1%, and 47.8%, respectively. These differences were of no statistical significance. The ratio of mild to severe vitreous haemorrhage during the first 4 days and after 4 weeks was 79% to 21% and 82% to 18% in the treatment group and 76.7% to 23.3% and 78.3% to 21.7% in the control group respectively, which showed no statistically significant difference. CONCLUSION: Tranexamic acid, with the method of administration in this study, had no effect on reducing early postvitrectomy haemorrhage in diabetic patients.

Adult↗

Short-term tranexamic acid treatment in aneurysmal subarachnoid hemorrhage.

Antifibrinolytic treatment for 4 weeks after a subarachnoid hemorrhage has been shown to have no effect on outcome since a reduction in the rate of rebleeding was offset by an increase in ischemic events. To determine if a shorter course (4 days) of antifibrinolytic treatment before the expected onset of ischemic complications might reduce the rate of rebleeding yet avoid ischemic complications, we prospectively studied a series of 119 patients with subarachnoid hemorrhage; 479 patients with subarachnoid hemorrhage from our previous randomized double-blind study (238 treated with placebo, 241 with long-term tranexamic acid) served as historical control groups. At 3 months' follow-up, the outcome of patients treated with short-term tranexamic acid was not different from that of patients treated with long-term tranexamic acid. The rate of rebleeding (24 of 119, 20%) was near that with placebo (56 of 238, 24%). In contrast, the rate of cerebral infarction (33 of 119, 28%) was almost identical to that after long-term tranexamic acid (59 of 241, 24%), although mortality from cerebral infarction was reduced. Compared with historical control groups, treatment with tranexamic acid for 4 days fails to reduce the incidence of rebleeding but still increases the rate of cerebral infarction.

Cerebral Angiography↗

A comparative study of the postoperative allogeneic blood-sparing effect of tranexamic acid versus acute normovolemic hemodilution after total knee replacement.

UNLABELLED: Both acute normovolemic hemodilution (NVHD) and tranexamic acid (TA) are potentially useful allogeneic blood conservation strategies after total knee replacement. However, the relative efficacy of these blood-sparing techniques is unknown. Therefore, to compare the postoperative allogeneic blood sparing of NVHD and TA after total knee replacement, we investigated 40 patients in a prospective, single-blinded study protocol. In Group TA, 30 min before deflating the limb tourniquet, an IV infusion of TA, 15 mg/kg, was administered over a 30-min period. Thereafter, a constant IV infusion of 10 mg x kg(-1) x hr(-1) was administered until 12 h after deflation of the limb tourniquet. Before induction of anesthesia, NVHD patients were bled to a target hematocrit of approximately 28%. Intravascular blood volume was maintained with lactated Ringer's solution. All autologous blood was transfused at the end of the surgery. Postoperatively, hematocrit was measured daily. In all cases, a hematocrit <27% was the postoperative transfusion trigger. Before discharge, deep vein thrombosis was excluded by Echo Doppler. Three months after surgery, the incidence of delayed thromboembolic events was assessed. The two groups were demographically comparable. In Group NVHD, 843 mL+/-289 of autologous blood was removed. Despite autologous blood transfusion, during the early postoperative period and until the third postoperative day, the NVHD group had significantly (P < 0.01) lower mean hematocrits when compared with the TA group. Thereafter, because of a significantly (P < 0.0008) greater allogeneic blood requirement in the NVHD group, no statistically significant difference in mean hematocrit recordings was noted among the groups. Blood accumulation in the surgical drain 12 h postoperatively, was significantly (P < 0.0008) higher in the NVHD group (259 mL+/-156) when compared with the TA group (110 mL+/-62). Significantly (P < 0.0008) more allogeneic blood was transfused in the NVHD group (19 U/13 patients) when compared with the TA group (2 U/2 patients). No abnormal Echo Doppler studies were reported. During the 3-mo follow-up period, a deep vein thrombosis and pulmonary embolus were documented in one patient in the NVHD group. We conclude that perioperative hemodynamic stability and allogeneic blood sparing is superior after tranexamic acid administration when compared with normovolemic hemodilution. IMPLICATIONS: For total knee replacement, when compared with normovolemic hemodilution, tranexamic acid administration is associated with superior perioperative hemodynamic stability and allogeneic blood sparing.

Aged↗

[Tranexamic acid in the prevention of oropharyngeal radiomucositis].

The therapeutic effect of tranexamic acid in prevention of radiomucositis has been evaluated in a double blind study. The results suggest that tranexamic acid can be the useful for the treatment of radiomucositis in head and neck cancer patients submitted to radiotherapy.

Cyclohexanecarboxylic Acids↗

Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination?

BACKGROUND: Children with cyanotic heart disease undergoing cardiac surgery in which cardiopulmonary bypass is used are at increased risk of postoperative bleeding. In this study, the authors investigated the possibility of reducing postoperative blood loss by using aprotinin and tranexamic acid alone or a combination of these two agents. METHODS: In a prospective, randomized, blind study, 100 children undergoing cardiac surgery were investigated. In group 1 (n = 25) patients acted as the control and did not receive either study drugs. In group 2 (n = 25) patients received aprotinin (30.000 KIU.kg(-1) after induction of anesthesia, 30.000 KIU.kg(-1) in the pump prime and 30.000 KIU.kg(-1) after weaning from bypass). In group 3 (n = 25) patients received tranexamic acid (100 mg.kg(-1) after induction of anesthesia, 100 mg.kg(-1) in the pump prime and 100 mg.kg(-1) after weaning from bypass). In group 4 (n = 25) patients received a combination of the two agents in the same manner. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. In addition, hemoglobin, platelet counts and coagulation studies were recorded. RESULTS: Postoperative blood loss was significantly higher in the control group (group 1) compared with children in other groups who were treated with aprotinin, tranexamic acid or a combination of the two agents (groups 2, 3 and 4) during the first 24 h after admission to cardiac intensive care unit (40 +/- 18 ml.kg(-1).24 h(-1), aprotinin; 35 +/- 16 ml.kg(-1).24 h(-1), tranexamic acid; 34 +/- 19 ml.kg(-1).24 h(-1), combination; 35 +/- 15 ml.kg(-1).24 h(-1)). The total transfusion requirements were also significantly less in the all treatment groups. Time taken for sternal closure was longer in the control group (68 +/- 11 min) compared with treatment groups 2, 3 and 4, respectively (40 +/- 18, 42 +/- 11, 42 +/- 13 min, P < 0.05). The coagulation parameters were not found to be significantly different between the three groups. CONCLUSIONS: Our results suggested that both agents were effective to reduce postoperative blood loss and transfusion requirements in patients with cyanotic congenital heart disease. However, the combination of aprotinin and tranexamic acid did not seem more effective than either of the two drugs alone.

Antifibrinolytic Agents↗

Absorption and elimination of alpha-thrombin and tranexamic acid after fibrin sealant application on resected livers in rabbits.

Maximum blood concentrations (Cmax) of thrombin and tranexamic acid were evaluated in the bloodstream after local application of a radioactively labelled cryoprecipitate based fibrin (CBF) sealant to a partial liver resection in rabbits. The Cmax of 3H-tranexamic acid reached a peak of 0.015 mg/ml of plasma after 1 h and then slowly cleared within 10 h, never reaching pharmacologically active systemic levels, and demonstrating a slow release from the clot and a fast clearance for the drug. The Cmax of 125I-alpha-thrombin never exceeded 56 milliunits of thrombin equivalent per ml, lower than endogenous thrombin generated in abdominal surgery. Furthermore, the low ratio of trichloroacetic acid precipitable counts versus total counts indicates that the majority of thrombin proteins are in a continuous process of degradation into very small peptides, which are known to be biologically inactive. The bioavailability of tranexamic acid, when embedded in a fibrin sealant, is much longer than when intravenously administered. Conversely, the circulating thrombin resulting from the sealant is low-molecular-weight degradation products with probably no significant biological activity.

Absorption↗

Tranexamic acid is effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations: a double-blind, randomized, placebo-controlled trial.

UNLABELLED: We evaluated the effects of tranexamic acid (TA) administered before and after cardiopulmonary bypass (CPB) in a prospective, randomized, placebo-controlled, double-blind study of adult patients undergoing primary coronary artery bypass grafting surgery. Patients received placebo (n = 30) or TA 15 mg/kg before CPB, followed by a TA infusion of 1 mg x kg(-1) x h(-1) for 5 h (n = 30) or TA 15 mg/kg after CPB, followed by a TA infusion of 1 mg x kg(-1) x h(-1) for 5 h (n = 30). Demographic, medical, surgical, laboratory, mediastinal chest tube drainage (MCTD), hemoglobin loss, transfusion, and outcome data were collected. Allogenic blood product administration was tightly controlled. The demographic, medical, and surgical characteristics were similar in all three groups. The median postoperative MCTD and hemoglobin loss in the pre-CPB TA group (710 mL, 8.6 g) was significantly less (P < 0.001) compared with the control (1202 mL, 44.2 g) and post-CPB TA groups (1020 mL, 23.4 g). The percentage of patients who received no allogenic blood products was 27% for the pre-CPB TA group and 33% for the post-CPB TA group (not significant). These percentages were significantly lower than those in the placebo group (66%, P < 0.001). The median number of allogenic blood products administered to the pre-CPB TA group (0 units) was significantly less compared with the control group (4.5 units). The thromboelastogram and fibrinogen split product levels in the pre-CPB TA group indicated better platelet function and less activation of the fibrinolytic system compared with the other two groups (P < 0.05). There were no intergroup differences in reoperation, myocardial infarction, stroke, infections, or death. These data support the use of pre-CPB TA to decrease patient exposure to postcardiopulmonary bypass allogenic blood products. IMPLICATIONS: In this randomized, placebo-controlled trial, we investigated the efficacy of tranexamic acid to decrease bleeding and blood transfusions after open-heart operations. Tranexamic acid administered before and during the operation was effective in decreasing both bleeding and transfusions. When tranexamic acid was administered immediately after the operation, it had a minor beneficial effect.

Aged↗

Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients.

BACKGROUND: Pharmacologic intervention to minimize postbypass bleeding and blood product transfusions has received increasing attention for both medical and economic reasons. METHODS: Two hundred ten patients were entered into a double-blinded, prospective, randomized study to receive either 10 g of fibrinolytic inhibitor tranexamic acid before incision (n = 104) or 250 mL of placebo saline solution (n = 106). All subjects requiring cardiopulmonary bypass were deemed suitable, including those having first-time coronary bypass grafting, valve replacement, and reoperation. RESULTS: There were no statistically significant differences between the groups with respect to demographic or operative characteristics. The tranexamic acid group had a 48% reduction in 24-hour blood drainage (p < 0.001) and received 69% fewer total units of packed red blood cells, 83% fewer total units of plasma, and 75% fewer platelet transfusion units than controls. Only 13 of 104 tranexamic acid patients received blood products versus 33 of 106 controls (p < 0.001). The incidences of thrombotic complications, perioperative myocardial infarction, renal failure, and neurologic complications were not significantly different between the two groups. The tranexamic acid group had 0% mortality versus 1.9% for controls (not significant). CONCLUSIONS: Tranexamic acid is safe and effective in reducing blood loss and blood use in a wide variety of cardiac surgical patients.

Aged↗

Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients.

BACKGROUND: A blood transfusion is a costly transplantation of tissue that may endanger the health for the recipient. Blood transfusions are common after total hip arthroplasty. The total saving potential is substantial if the blood loss could be reduced. Studies on the use of tranexamic acid have shown interesting results, but its benefits in total hip arthroplasty have not yet been resolved. PATIENTS AND METHODS: 100 patients receiving a total hip arthroplasty (THA) got a single injection of tranexamic acid (15 mg/kg) or placebo intravenously before the start of the operation. The study was double-blind and randomized. Total blood loss was calculated from the hemoglobin (Hb) balance. Volume and Hb concentration of the drainage was measured 24 h after the operation. Intraoperative blood loss was estimated volumetrically and visually. RESULTS: The patients who received tranexamic acid (TA) bled less. The total blood loss was on average 0.97 L in the TA group and 1.3 L in the placebo group (p < 0.001). 8/47 (0.2) in the TA group were given blood transfusion versus 23/53 (0.4) in the placebo group (p = 0.009). Drainage volume and drainage Hb concentration were less in the TA group (p < 0.001 and p = 0.001). No thromboembolic complications occurred. INTERPRETATION: Considering the cost of blood and tranexamic acid only, use of the drug would save EUR 47 Euro per patient. We recommend a preoperative single dose of tranexamic acid for standard use in THA.

Aged↗

Prevention of severe bleeding by tranexamic acid in a patient with disseminated intravascular coagulation.

Severe bleeding took place in a patient when abdominal aneurysm was removed by operation. Bleeding continued after infusion of heparin, antithrombin III (ATIII), fresh platelets and fresh blood. Infusion of tranexamic acid resulted in an immediate cessation of bleeding and improvement of his general condition. Sometime after the cessation by the administration of tranexamic acid, severe bleeding started again, resulting in intraperitoneal hematoma formation. Second time bleeding also stopped after the administration of tranexamic acid. Major finding of plasma parameters of fibrinolysis is that alpha 2AP which had been unable to inhibit plasmin, became able to inhibit it after the administration of tranexamic acid.

Aged↗

The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement.

STUDY OBJECTIVE: To assess the influence of tourniquet inflation-deflation as well as desmopressin and tranexamic acid (TA) administration on prothrombin fragment 1.2, fibrinogen, plasmin antiplasmin complex, and D-dimer concentrations during total knee replacement. DESIGN: Randomized, placebo-controlled study. SETTING: Large referral hospital. PATIENTS: 30 ASA physical status I, II, and III patients undergoing total knee replacement. INTERVENTIONS: Patients were randomized to one of three treatment groups. Patients received either tranexamic acid, desmopressin, or an equal volume of saline, intravenously. MEASUREMENTS AND MAIN RESULTS: Cubital blood was drawn immediately before induction of anesthesia, 1 hour after tourniquet application, and 2 and 15 minutes after tourniquet deflation. Fibrinogen and D-dimer levels were measured using the Clauss Method and latex agglutination, respectively. Plasmin antiplasmin complex and prothrombin fragment 1.2 levels were measured by enzyme-linked immunosorbent assay (ELISA). All assays were performed in duplicate, and intra-assay variability was documented. No statistically significant difference in fibrinogen, D-dimer, plasmin antiplasmin complex, or prothrombin fragment 1.2 levels was demonstrated among the groups. Similarly, within each group there were no statistically significant differences in the variables studied. However, despite the lack of statistical significance, when compared with their levels during tourniquet application, an increase in D-dimer and plasmin antiplasmin complex levels was observed in all three groups at 2 and 15 minutes after tourniquet release. In contrast, no increase in prothrombin fragment 1.2 generation was noted. Significantly more allogeneic blood was transfused in the Control and Desmopressin Groups when compared with the tranexamic acid group (p< 0.02). CONCLUSIONS: No evidence of tourniquet-induced fibrinolysis or thrombin generation was demonstrated in the systemic circulation. Desmopressin and tranexamic acid had no significant effect on the variables measured.

Aged↗

A double-blind study on the influence of tranexamic acid on the intraocular pressure and the central corneal thickness after trabeculectomy for glaucoma simplex.

The influence of tranexamic acid on the intraocular pressure and central corneal thickness has been examined by means of a double-blind trial in patients with glaucoma simplex. The material comprised 28 patients (14 pairs) who had all been operated on for glaucoma in one eye by trabeculectomy. Tranexamic acid was found not to influence the intraocular pressure, neither in the operated eye nor in the opposite eye. The possible antifibrinolytic effect on the outflow of the aqueous humour is discussed. As in previous studies an effect of tranexamic acid on the central corneal thickness was found in both the operated and in the non-operated eye. A possible mechanism behind this is discussed.

Aged↗

Inhibition by tranexamic acid of the conversion of single-chain tissue plasminogen activator to its two chain form by plasmin: the presence on tissue plasminogen activator of a site to bind with lysine binding sites of plasmin.

The addition of tranexamic acid inhibited the conversion of single chain tissue plasminogen activator (sct-PA) to its two chain form (tct-PA) by plasmin. Increase in the concentrations of tranexamic acid resulted in more inhibition of the conversion, with 50% inhibition being obtained at 0.251 mM of the concentration of tranexamic acid. The addition of the fragments of plasminogen such as kringle 1 to 3 (K1-3), and K4 resulted in the facilitation of the conversion of sct-PA to tct-PA by plasmin. The addition of tranexamic acid to the mixture of sct-PA and K4 inhibited the rate of the conversion of sct-PA by plasmin. These results suggest that binding of lysine binding sites of plasmin or plasminogen with sct-PA enhanced its conversion to tct-PA by plasmin, and that there is a site on a t-PA molecule to bind to plasminogen or plasmin.

Animals↗

Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation.

BACKGROUND: Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Amoxicillin-related postextraction bleeding in an anticoagulated patient with tranexamic acid rinses.

This report describes a patient who had significant postoperative bleeding 4 days after undergoing surgery while using a tranexamic acid (4.8%) mouth rinse protocol for local control of hemostatis. Patients undergoing dentoalveolar surgery who are receiving chronic oral anticoagulants are treated with a tranexamic acid mouth rinse at our hospital. No systemic modification of their coagulation status is attempted. The postoperative bleeding problem that developed was determined to be caused by an antibiotic-induced vitamin K deficiency rather than a failure of the tranexamic acid protocol.

Aged↗

Does tranexamic acid reduce desmopressin-induced hyperfibrinolysis?

OBJECTIVE: Desmopressin releases tissue-type plasminogen activator, which augments cardiopulmonary bypass--associated hyperfibrinolysis, causing excessive bleeding. Combined use of desmopressin with prior administration of the antifibrinolytic drug tranexamic acid may decrease fibrinolytic activity and might improve postoperative hemostasis. METHODS: This prospective randomized study was carried out with 100 patients undergoing coronary artery bypass operations between April 1999 and November 2000 in Gülhane Military Medical Academy. Patients were divided into 2 groups. Desmopressin (0.3 microg/kg) was administrated just after cardiopulmonary bypass and after protamine infusion in group 1 (n = 50). Both desmopressin and tranexamic acid (before the skin incision at a loading dose of 10 mg/kg over 30 minutes and followed by 12 hours of 1 mg.kg(-1).h(-1)) were administrated in group 2 (n = 50). RESULTS: Significantly less drainage was noted in group 2 (1010 +/- 49.9 mL vs 623 +/- 41.3 mL, P =.0001). Packed red blood cells were transfused at 2.1 +/- 0.5 units per patient in group 1 versus 0.9 +/- 0.3 units in group 2 (P =.0001). Fresh frozen plasma was transfused at 1.84 +/- 0.17 units per patient in group 1 versus 0.76 +/- 0.14 units in group 2 (P =.0001). Only 24% of patients in group 2 required donor blood or blood products compared with 74% of those in the isolated desmopressin group (group 1, P =.00001). Group 1 and group 2 findings were as follows: postoperative fibrinogen, 113 +/- 56.3 mg/dL versus 167 +/- 45.8 mg/dL (P =.0001); fibrin split product, 21.2 +/- 2.3 ng/mL versus 13.5 +/- 3.4 ng/mL (P =.0001); and postoperative hemoglobin level, 7.6 plus minus 1.2 g/dL versus 9.1 plus minus 1.2 g/dL (P =.0001). CONCLUSION: Tranexamic acid administration significantly reduces desmopressin and bypass-induced hyperfibrinolysis. Combined use of tranexamic acid and desmopressin decreases both postoperative blood loss and transfusion requirement.

Aged↗

The effect of tranexamic acid on the quality of life of women with heavy menstrual bleeding.

OBJECTIVE: To investigate whether medical treatment with tranexamic acid would increase the quality of life of women with heavy menstrual bleeding. STUDY DESIGN: This open, uncontrolled usage study included 849 women diagnosed with heavy menstrual bleeding and considered eligible for tranexamic-acid treatment. The condition of the women was investigated at baseline and after the first and the third treated menstruation. Quality of life and subjectively experienced state of health were assessed with the aid of a questionnaire. Satisfaction with the treatment was registered. RESULTS: After the third menstruation, 80% of the women were satisfied with the treatment. Impairment of social activities and impairment at work were greatly reduced by the treatment. Substantial improvements were also recorded with regard to alertness, productivity, cleanliness, spirits, action radius and overall well-being. Adverse reactions to the drug used for the treatment were few and non-serious. CONCLUSIONS: Medical treatment with tranexamic acid increases quality of life for women with heavy menstrual bleeding.

Adolescent↗

Inhibition of tumour vascularization by tranexamic acid. Experimental studies on possible mechanisms.

The vascularization of an intramuscularly transplanted rat sarcoma was studied by microangiography. Administration of tranexamic acid as well as of indomethacin reduced the vascular connections between tumour and surrounding normal muscle. These drugs also reduced tumour growth rate irrespective of whether they were administered early or late during tumour growth. An electron microscopy study of tumour specimens from animals given tranexamic acid did not reveal any degenerative vascular changes. One explanation of the inhibition of tumour growth and vascularization by tranexamic acid and by indomethacin may be reduction of a local inflammatory reaction induced by tumour transplantation and stimulating tumour vascularization.

Angiography↗