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Traumatic hyphaema treated with the antifibrinolytic drug tranexamic acid II.

During the year 1976 (January 1st to December 31st) 75 patients, consecutively admitted to the eye department of Arhus Kommunehospital with traumatic hyphaema, were treated with the antifibrinolytic drug tranexamic acid. No secondary haemorrhage occurred. The patients were not confined to bed. The eyes were not patched and the activities of the patients were not restricted. In a previous series from 1975 where the patients were confined to bed but otherwise treated identically with tranexamic acid one out of 72 patients had a secondary haemorrhage. When the two materials are combined one out of 147 patients had a secondary haemorrhage corresponding to 0.68%.

Adolescent↗

Effects of tranexamic acid and urokinase on hematogenous metastases of Lewis lung carcinoma in mice.

When Lewis lung carcinoma with low thromboplastic and low fibrinolytic activities was implanted subcutaneously to mice, administration of tranexamic acid inhibited metastasis formation in the lungs. This effect was considered to be mediated by prevention of cell release from the implanted sites. Fibrin formation around tumor cells in the vessels of primary foci was observed in the mice given tranexamic acid. On the other hand, urokinase significantly enhanced pulmonary metastases and many free tumor cells were observed intravascularly in primary foci of the mice given urokinase.

Animals↗

Tranexamic acid reduces bleeding and the need for blood transfusion in primary myocardial revascularization.

BACKGROUND: The objective of this study was to study the effect of low-dose tranexamic acid (TA) on postoperative bleeding and coagulation variables after coronary artery bypass grafting operation. METHODS: Fifty patients undergoing primary coronary artery bypass grafting were randomly assigned to receive either placebo (0.9% NaCl; n = 25) or 10 mg/kg TA followed by infusion of 1 mg/kg per hour during the operation (n = 25). Data measured included blood loss, transfusion, reoperation, fibrinogen level, fibrinogen split products, platelet size, and platelet function. Measurements were made after induction of anesthesia, after heparin administration, during patient warming, after skin closure, and 24 hours after operation. RESULTS: Patients in the TA study group weighed less. Other demographic characteristics were similar between groups. Postoperative bleeding was less in the TA group (194 +/- 135 mL versus 488 +/- 238 mL, p < 0.001), whereas blood requirement was higher in the control group (1.68 +/- 1 versus 0.52 +/- 0.9 U of packed cells per patient, p < 0.001). The percent of patients exposed to blood products was significantly less in the TA group (36% versus 100%, p < 0.001). Fibrinogen split products were lower in the TA group during bypass (p < 0.001). Fibrinogen levels fell in both groups during cardiopulmonary bypass. Platelet number and function were reduced equally in both groups by cardiopulmonary bypass. Other test results were not different between groups. CONCLUSIONS: The use of low-dose TA during coronary artery bypass grafting significantly reduced the coagulopathy-induced postoperative bleeding and allogeneic blood products requirement. The low levels of fibrinogen split products during bypass in the study group reflect the inhibiting effect of TA in fibrinolysis. Tranexamic acid had no effect on platelet function during cardiopulmonary bypass.

Aged↗

[The use of tranexamic acid as an anesthetic component in ENT surgeries in patients with high surgical-anesthetic risk and in hemorrhagic shock intensive therapy].

Experimental and clinical trials have shown that anesthesia and intensive therapy of shock incorporating tranexamic acid enhance analgesia, hyporeflexia, thus ensuring stable, adequate anesthesia which is safe under reduced doses of standard anesthesiological modalities. Application of tranexamic acid provided more favourable course of postanesthesiological and postoperative periods, decreased the number of complications and lethal outcomes compared to standard anesthesia.

Adult↗

Tranexamic acid in paediatric cardiac surgery.

BACKGROUND & OBJECTIVES: Antifibrinolytic agents are used commonly in adult cardiac surgery to reduce postoperative blood loss. Paucity of literature on the use of a newer antifibrinolytic agent tranexamic acid (TA) in children undergoing cardiac surgery promoted us to conduct this study in children with cyanotic heart disease. METHODS: One hundred and twenty consecutive children with cyanotic heart disease were randomised into two groups. Control (group A) (n=24) given no drug while the study (group B, n=96) group was given tranexamic acid 10 mg/kg each after anaesthetic induction, on bypass and after protamine at the end of bypass. Postoperatively, total mediastinal chest tube drainage and blood and blood product usage at 24 h were recorded. Tests of coagulation including activated clotting time, fibrinogen, fibrin degradation products and platelet count were performed at 6 h postoperatively. RESULTS: The two groups were comparable in terms of demographic characteristics such as age, sex, weight, operations performed, and preoperative haematocrit. Postoperatively, group B, had a significantly (P<0.05) lower blood loss, blood and blood product usage, re-exploration rate compared to the control group. There was preservation of fibrinogen and lower levels of fibrin degradation products in group B. INTERPRETATION & CONCLUSION: Tranexamine acid was highly effective in reducing post-operative blood loss, blood and blood product usage in children with congenital cyanotic heart disease undergoing corrective surgery.

Adolescent↗

The hemostatic effect of tranexamic acid in conisatio colli uteri.

To evaluate the inhibitory effect of tranexamic acid (AMCA) on increased fibrinolyctical activity in connection with conisatio colli uteri we have carried out a randomized, double-blind study with patients operated upon partly with an open method of operation (80 patients) and partly with modified Sturmdorff sutures (150 patients). In connection with the open method the frequency of late bleeding decreased from 17.5% to 2.5%, which is significant. The corresponding decrease in connection with the other method was from 10.7% to 4.1%. This material was not sufficiently large to verify significance. The side effects of the prophylactic treatment with AMCA were few. The study indicates that AMCA affords good protection against late bleeding in conisatio colli uteri.

Adult↗

Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease.

In a double-blind trial tranexamic acid (AMCA, Cyclokapron), 1 g three times a day for five days, significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease. No side effects were seen in either group of patients. Screening tests showed no toxic action of tranexamic acid on the liver, kidney, or heart.

Adolescent↗

Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic acid.

Treatment of a haemorrhagic shock after just a single dose of fondaparinux in an orthopaedic patient with reduced renal clearance is presented. Since all routine haemostatic parameters were nearly normal, single doses of rFVIIa (90 microg/kg) and of tranexamic acid (15 mg/kg) were administered to improve thrombin generation and reduce fibrinolysis. This case is the first showing the effectiveness of combining single doses of rFVIIa and tranexamic acid in controlling severe postoperative bleeding after fondaparinux.

Aged↗

Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.

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.

Aminocaproic Acid↗

Prophylactic administration of tranexamic acid preserves platelet numbers during extracorporeal circulation in rabbits.

Neonatal extracorporeal life support is associated with platelet consumption and hemostatic disorders. This study in rabbits was undertaken to evaluate the effect of heparin coating and of the plasminogen and plasmin inhibitor, tranexamic acid on platelet consumption during extracorporeal circulation. Fibrinogen consumption was prevented by heparin coating, but platelet consumption was only prevented after the prophylactic administration of tranexamic acid. The authors concluded that inhibition of the fibrinolytic system had a specific effect on preserving platelet numbers, rather than improving the thromboresistance of the artificial surface. The main advantage of a heparin coating is the anticoagulant activity of the surface. Thus systemic heparinization can be reduced or omitted.

Animals↗

Blood loss following dental extractions in anticoagulated rabbits: effects of tranexamic acid and socket packing.

The present study demonstrates the feasibility of chronic anticoagulation in rabbits and of estimating the resulting increase in blood loss following extraction of four front teeth from labeled red cell disappearance curves. This setup proved useful for the evaluation of hemostatic techniques. Socket packing with oxidized cellulose soaked in thrombin solution or local application of cyanobutylacrylate reduced early blood loss; oral administration of tranexamic acid reduced both early and late bleeding; the combination of socket packing and oral tranexamic acid completely abolished the excessive blood loss that resulted from anticoagulation alone.

Administration, Oral↗

Liquid chromatography-tandem mass spectrometry method for the determination of tranexamic acid in human plasma.

A new method for the determination of tranexamic acid (TA) in human plasma using high performance liquid chromatography with tandem mass spectrometric detection was described. TA and the internal standard, methyldopa, was extracted from a 200 l plasma sample by a one-step deproteination using perchloric acid. Chromatographic separation was performed on an Xtrra MS C18 Column (2.1 mm x 100 mm, 3.5 microm) with the mobile phase consisting of 10% acetonitrile in 2 mM ammonium acetate buffer (pH 3.5) at a flow rate of 0.15 ml/min. The total run time was 5 min for each sample. Detection and quantitation was performed by the mass spectrometer using the multiple reaction monitoring of the precursor-product ion pair m/z 158 --> 95 for TA and m/z 212 --> 166 for methyldopa, respectively. The method was linear over the concentration range of 0.02-10.00 g/ml with lower limit of quantification of 0.02 microg/ml for TA. The intra- and inter-day precision was less than 11% and accuracy ranged -10.88 to 11.35% at the TA concentrations tested. The present method provides a relatively simple and sensitive assay with short turn-around time. The method has been successfully applied to a clinical pharmacokinetic study of TA in 12 healthy subjects.

Calibration↗

Treatment with tranexamic acid during pregnancy, and the risk of thrombo-embolic complications.

Tranexamic acid (AMCA) is an inhibitor of fibrinolysis used to treat fibrinolytic bleeding (e.g., menorrhagia and gastro-intestinal haemorrhage), and to prevent bleeding at surgery, in cases of abruptio placentae and general haemorrhage. As AMCA stabilises preformed clots and prolongs their dissolution, it has been debated whether treatment with AMCA might predispose to thrombosis by depressing the fibrinolytic system. Pregnant women constitute a group with low fibrinolytic capacity and an increased frequency of thrombosis further increased after Caesarean section, and are thus more likely to be susceptible to antifibrinolytic therapy. We therefore carried out a retrospective analysis of the case records of 2,102 patients with various bleeding disorders during pregnancy. Of the 256 patients treated with AMCA (mean duration of treatment, 46 days), 169 were delivered by Caesarean section. Of the remaining 1,846 patients (i.e., controls), 443 were delivered by Caesarean section. The relationship between the use of AMCA and the occurrence of thrombo-embolism was calculated with 95% confidence limits. Of the AMCA treated group (n = 256), two patients--one of whom belonged to the Caesarean section subgroup (n = 168)--had pulmonary embolism. Of the controls (n = 1,846), three patients had deep vein thrombosis and one had pulmonary embolism, all four cases belonging to the Caesarean section subgroup (n = 443). Thus, the findings in this high risk group of women with complicated pregnancies, frequently entailing delivery by Caesarean section, provided no evidence of any thrombogenic effect of AMCA.

Abruptio Placentae↗

[Usefulness of tranexamic acid in cranial remodeling surgery].

OBJECTIVES: To assess the usefulness of tranexamic acid (TA) in pediatric cranial remodeling surgery, by analyzing its effects on bleeding and transfusion requirements, number of days of cranial drainage required, and time spent in the postoperative recovery unit. MATERIAL AND METHOD: A single-blind, controlled study was designed with 20 patients (10 cases and 10 controls) randomly assigned to receive or not receive 15 mg/kg of intravenous TA upon anesthetic induction, every 4 hours during surgery, and every 8 hours throughout the 48 hours after surgery. Variables analyzed were results of blood tests, blood loss, volume transfused, time in the recovery unit, and complications related to TA infusion. RESULTS: The group treated with TA experienced less bleeding during surgery than did the controls (199 +/- 60 vs 290 +/- 43 mL) and had less need of intraoperative (176 +/- 104 vs 206 +/- 70 mL) and postoperative transfusion (9 +/- 28 vs 52 +/- 72 mL) 24 hours after surgery. TA group patients also spent less time in the recovery unit (60 +/- 14 vs 72 +/- 11 hours). Blood test variables in TA-treated children were also better 24 hours after surgery with regard to hemoglobin (12.1 +/- 2 vs 11.6 +/- 1.3 mg/dL) and platelet (261 +/- 68.5 vs 181.6 +/- 58.1 platelets/mm3) concentrations, and cephalin time (33 +/- 12 vs 49 +/- 16 seconds). No complications related to TA treatment were observed. CONCLUSIONS: TA can reduce perioperative bleeding in the context of pediatric cranial remodeling surgery. TA-treated patients have less need of transfusion and this may reduce the rate of related complications as well a make care more efficient.

Anesthesia Recovery Period↗

Does salvage and tranexamic acid reduce the need for blood transfusion in revision hip surgery?

We carried out a retrospective case-control study in 80 patients who underwent a revision total hip replacement. Group A (40 patients) received tranexamic acid and intra-operative cell salvage. Group B (40 patients) was a matched control group and did not receive this management. Each group was divided into four subgroups: revision of both components, revision of both components with bone grafting, revision of the acetabular component with or without bone graft, and revision of the femoral component with or without bone graft. In group A the total number of units transfused was 52, compared with 139 in group B, representing a reduction in blood usage of 62.5%. The mean amount of blood transfused from cell salvage in each group was 858 ml (113 to 2100), 477 ml (0 to 2680), 228 ml (75 to 315) and 464 ml (120 to 1125), respectively. There was a significant difference in the amount of blood returned between the groups (p < 0.0001). In group A, 22 patients needed transfusion and in group B, 37 (p < 0.0001). A cost analysis calculation showed a total revenue saving of pounds sterling 70 000 and a potential saving throughout our facility of pounds sterling 318 288 per year. Our results show that a significant reduction in blood transfusion can be made using combined cell salvage and tranexamic acid in revision surgery of the hip.

Analysis of Variance↗

Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats.

BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.

Animals↗

Oral administration of tranexamic acid in the management of traumatic hyphema in children.

In a prospective study 163 patients aged 17 years or less admitted to a children's hospital between April 1985 and December 1990 with traumatic hyphema were treated with tranexamic acid, 25 mg/kg given orally every 8 hours to a maximum of 1500 mg every 8 hours for 5 days. Secondary hemorrhage occurred in 5 patients (3%), none of whom had more than one rebleeding episode. In contrast, 24 (8%) of 316 patients aged 17 years or less admitted to the same hospital between January 1977 and March 1985 with traumatic hyphema who were not treated with antifibrinolytics had a secondary hemorrhage, several more than once, giving a rebleeding rate of 33/316 (10%). The results suggest that tranexamic acid reduces the incidence and number of secondary hemorrhages in children, without significant ocular or systemic side effects.

Administration, Oral↗

Hemostatic parameters and platelet activation marker expression in cyanotic and acyanotic pediatric patients undergoing cardiac surgery in the presence of tranexamic acid.

We have investigated hemostatic parameters including platelet activation in 56 pediatric patients with or without cyanosis undergoing cardiopulmonary bypass (CPB) and cardiac surgery to repair congenital defects. Patients were participants in a study assessing the effects of tranexamic acid on surgery-related blood loss. Parameters monitored included blood loss, prothrombin F1.2, thrombin-antithrombin complexes, t-PA, PAI-1, plasminogen, fibrin D-dimer, and plasma factor XIII. Additionally, flow cytometry monitored platelet degranulation (P-selectin or CD63), as well as surface-bound fibrinogen, von Willebrand factor and factor XIIIa. Cyanotic patients had evidence of supranormal coagulation activation as both fibrin D-dimer and PAI-1 levels were elevated prior to surgery. While the extent of expression of P-selectin or CD63 was not informative, platelet-associated factor XIIIa was elevated in cyanotic patients at baseline. In both patient groups, CPB altered platelet activation state and coagulation status irrespective of the use of tranexamic acid.

Antifibrinolytic Agents↗