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Determination of tranexamic acid in human serum by high-performance liquid chromatography using selective pre-column derivatization with phenyl isothiocyanate.

A high-performance liquid chromatographic method for determination of tranexamic acid in human serum using a selective derivatization has been developed. Tranexamic acid in the sample was allowed to react with phenyl isothiocyanate to form the phenylthiocarbamoyl derivative. Interfering alpha-amino acids in the sample were eliminated by selective derivatization to phenylthiohydantoin derivatives by acid treatment of the phenylthiocarbamoyl derivatives followed by solvent extraction. Then, the sample was analysed by conventional high-performance liquid chromatography with ultraviolet detection. The limit of detection of this method for serum sample was 0.2 micrograms/ml at a signal-to-noise ratio of 2. This method gave results comparable with those obtained by amino acid analysis (regression line: y = 0.4531x-0.02596, r = 0.9998, n = 21).

Amino Acids↗

Feline generalized epilepsy induced by tranexamic acid (AMCA).

Epileptic activities induced by topical application of tranexamic acid (AMCA) and penicillin to the cortex of 12 cats in acute experiments were compared. Both substances when diffusely applied on a wide cortical area of both hemispheres at very low concentration produced an EEG pattern consisting of spike-wave bursts similar to the electrographic manifestations seen in feline generalized epilepsy induced by large parenteral doses of sodium penicillin. These epileptic bursts could be triggered by repetitive stimulation of nucleus centralis medialis. Increased concentrations of both AMCA and penicillin led to the appearance of bilaterally synchronous spikes and poly-spikes which were not further excited by NCM stimulation. Two factors seem to play an important role in eliciting spike-wave bursts in both models: (1) the area of the cortex exposed to the epileptogenic agent and (2) the concentration of the epileptogenic agent used. The similar effects observed in 5 chronic animals either by intravenous injection of high doses of AMCA or by intramuscular injection of sodium penicillin confirm the results obtained in acute experiments and suggest a new way of inducing feline generalized epilepsy.

Administration, Topical↗

Regional hemostatic status and blood requirements after total knee arthroplasty with and without tranexamic acid or aprotinin.

UNLABELLED: Antifibrinolytics seem to reduce postoperative blood loss after total knee arthroplasty. Few studies have shown the impact of these drugs on the mechanisms of coagulation. The purpose of this study was to examine coagulation/fibrinolysis variables as well as blood loss after total knee arthroplasty with and without antifibrinolytics in the operated limb on a regional level. Thirty-six patients were randomized into one of three groups to receive aprotinin, tranexamic acid, or no medication. We took blood samples of the femoral vein before deflating the tourniquet and after 5, 10, 30, 60, 120 min and on the first postoperative day. The implantation of a knee prosthesis in artificial ischemia caused a significant activation of coagulation and fibrinolysis in the regional circulation. Tranexamic acid and aprotinin did not cause a significant modulation of fibrinolysis variables or a significant reduction of postoperative bleeding and transfusion requirements. One of the differences in comparison to other studies was the decreased total blood loss. The use of bone cement as well as surgical hemostasis before wound closure may be regarded as reasons for this. Therefore, primarily these methods should be used because there is no increased risk of adverse drug effects. IMPLICATIONS: After total knee arthroplasty total blood loss may be kept in a low range if methods such as cemented knee prosthesis and surgical hemostasis are used. In this case aprotinin and tranexamic acid did not cause a significant modulation of fibrinolysis variables or a significant reduction of postoperative bleeding.

Adult↗

Determination of plasma tranexamic acid using cation-exchange high-performance liquid chromatography with fluorescence detection.

A procedure is described for the determination of plasma tranexamic acid concentrations using cation exchange high-performance liquid chromatography with fluorescence detection following post-column derivatisation with omicron-phthalaldehyde. The chromatographic conditions were optimised with respect to detector performance and the method applied to measuring the plasma tranexamic acid levels of patients in a double-blind trial.

Chromatography, High Pressure Liquid↗

Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients.

INTRODUCTION: Extensive blood loss related to knee arthroplasty is quite normal and many patients require blood transfusions. Surgery and the use of pneumatic tourniquets lead to an increase in the activity of the fibrinolytic system, which in turn may accentuate the blood loss. Drugs that inhibit the fibrinolytic system may thus be used to reduce blood loss. Tranexamic acid (TA) acts by binding to one of the enzymes at the start of the coagulation cascade, so inhibiting the fibrinolytic system. A concern is that this inhibition may have the side effect of increasing thromboembolic disease, a common complication of joint replacement surgery. We aimed to confirm the reductions in blood loss and to assess the impact of TA usage on clinical and sub-clinical DVT. METHOD: We performed a prospective, randomised, double blind, controlled trial, using patients due to undergo primary unilateral total knee arthroplasty. Patients were randomised to receive either 15 mg/kg of tranexamic acid or a similar volume of normal saline at the time of cementing of the prosthesis. Perioperative blood loss was recorded and patients were screened for DVT with duplex ultrasound assessment of both legs on the fifth post-operative day. RESULTS: A statistically significant (p=0.006) decrease in blood loss in the early post-operative period was noted in the group receiving tranexamic acid. This was not associated with a significant difference in total blood loss (p=0.55) or in transfusion requirements. There was no of evidence in DVT in either group on duplex ultrasound screening of the lower limbs. INTERPRETATION: One injection of 15 mg/kg of tranexamic given at the time of cementing the prosthesis in total knee arthroplasty, before deflation of the tourniquet, significantly decreases the amount of blood loss in the early post-operative period. The treatment was not associated with an increase in thromboembolic complications.

Aged↗

[Hereditary angioneurotic edema: study of serum complement and therapeutic trial with tranexamic acid (author's transl)].

Three familial generations (five members with hereditary angioneurotic edema) have been evaluated under clinical and immunological standpoints. A therapeutic trial with tranexamic acid was carried out. The five members with hereditary angioneurotic edema showed: decreased values of total hemolytic activity (CH50), deficit of C4 (between 8 and 23 percent of the normal value), and normal levels of C3 and C9. C3PA was normal in four members and decreased in one. Asymptomatic familial members had normal serum complement levels; only three cases showed diminished values of CH50, C4, C-1-INH and C3PA. Therapeutic trial with tranexamic acid demonstrated the usefulness of this agent in the treatment of angioneurotic edema; it showed slighter adverse reactions than those derived from other therapeutic modalities. Screening of asymptomatic familial members is pointed out in order to detect low plasma values of C1-IHN.

Angioedema↗

Tranexamic acid and aprotinin reduce postoperative bleeding and transfusions during primary coronary revascularization.

UNLABELLED: 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.

Antifibrinolytic Agents↗

The effect of tranexamic acid on bleeding time and haemostasis.

The effect of tranexamic acid (TXA) on platelet function was examined in 37 patients with ruptured intracranial aneurysms. TXA was administered in a double-blind, placebo controlled manner to 37 patients with ruptured intracranial aneurysms. TXA was given to 17 patients in a dose of 9 g/24 hours, to another 6 patients in a dose of 6 g/24 hours; 14 patients were given a placebo. The effect of TXA on certain haemostatic function tests was evaluated between the treatment groups. We conclude that patients receiving TXA do not appear to be at risk of recurrent haemorrhage due to abnormal haemostasis.

Bleeding Time↗

No therapeutic effect of plasmin antagonist tranexamic acid in rheumatoid arthritis. A double-blind placebo-controlled pilot study.

OBJECTIVE: In the present study, the effects of plasmin antagonist tranexamic acid (TEA) on urinary pyridinoline excretion rates were investigated in rheumatoid arthritis (RA) patients. METHODS: The study was set up as a double-blind placebo-controlled pilot study. Ten patients received tranexamic acid and 9 received placebo for 12 weeks. Urinary excretion rates of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) were used as molecular markers of articular cartilage and bone degradation. In addition, clinical parameters of disease activity were assessed and CRP levels were measured. RESULTS: Treatment with TEA did not reduce pyridinoline excretion, nor was any effect observed on clinical parameters of disease activity or on CRP levels. CONCLUSION: The results of the present pilot study show no beneficial effect of TEA as adjuvant therapy in RA patients with respect to joint destruction or disease activity.

Amino Acids↗

The effect of tranexamic acid on secondary haemorrhage after traumatic hyphaema.

During the period from March 1978 to November 1979, 232 consecutive patients with traumatic hyphaema were allocated by admission-date to conservative treatment and to treatment with the antifibrinolytic drug tranexamic acid. Secondary haemorrhage occurred in only two of 102 tranexamic acid treated patients, while secondary haemorrhage occurred in 12 out of 130 conservatively treated patients. This difference was statistically significant. Some clinical aspects of the rebleeding cases are presented and briefly discussed.

Adolescent↗

Beneficial effect of both tranexamic acid and aprotinin on blood loss reduction in reoperative valve replacement surgery.

BACKGROUND: Blood loss after cardiac surgery is a continuing concern of caregivers and patients. The acute inflammatory reaction initiated by the extracorporeal circuitry, necessary to perform the procedure, stimulates the coagulation cascade, and the resultant hyperfibrinolysis is considered to be a major contributing factor of blood loss. The necessity to reduce transfused blood products after cardiac surgery is important, as it reduces the potential transmission of serious viral infections, improves operative outcomes, and provides containment of costs. The purpose of this study was to compare the effect of synthetic antifibrinolytic tranexamic acid with naturally occurring antifibrinolytic aprotinin on blood loss and to study requirements for transfusion of blood products after repeat cardiac valve surgery. METHODS AND RESULTS: Two randomized trials had been previously conducted, each comparing the respective treatment groups, aprotonin (AP group) and transexamic acid (TA group), with a control group [placebo (P)] in double-blind fashion with the same inclusion and exclusion criteria. The number of patients in the four designated groups are as follows: TA, 22; TA-P, 19; AP, 24; and AP-P, 36. The dosage of aprotinin (high-dose) encompassed a 280-mg loading dose infused after induction of anesthesia, 280 mg in the CPB prime solution, and 70 mg/h for a period of 6 hours. The tranexamic acid dose was 10 mg infused in 500 mL of normal saline. The blood loss was measured intraoperatively and postoperatively. The transfusion of homologous blood products was conducted in a standardized fashion. Both the TA and AP groups lost less blood intraoperatively, in total, less than either of the placebo groups, and less blood postoperatively than the TA-P group (P<.05). The postoperative blood loss (median) was 538 mL for the TA group, 455 mL for the AP group, and for the respective placebo groups, 1170 mL and 595 mL. The total blood loss was 1340 mL for the TA group, 1383 mL for the AP group, and 3250 mL and 2450 mL, respectively for the placebo groups. The total blood product use revealed no differences between the two placebo groups (P=NS) nor between the two treatment groups (P=NS). CONCLUSIONS: Tranexamic acid and aprotinin are both effective in reducing intraoperative and postoperative blood loss and the need for blood product transfusion for patients undergoing reoperative cardiac valvular surgery.

Adult↗

Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: Comparison between on-pump and off-pump techniques.

OBJECTIVES: Bleeding and inflammation are major complications of extracorporeal circulation. Off-pump coronary artery bypass grafting may reduce the rate of complications, but it can only be applied in selected cases. Pilot studies have shown a potential benefit from the use of antifibrinolytic drugs, but efficacy in randomized double-blind studies evaluating off- and on-pump coronary artery bypass grafting has not been proved. METHODS: We enrolled 102 patients scheduled for on-pump (n = 51) or off-pump (n = 51) coronary artery bypass grafting. Patients were separately double-blind randomly assigned to treatment with tranexamic acid (1 g as 20-minute bolus before skin incision, followed by continuous infusion of 400 mg/h, with 500 mg added to priming in patients undergoing on-pump coronary artery bypass grafting) or placebo (saline solution of equivalent volume). Bleeding in the first 24 postoperative hours was the primary outcome. Requirement for allogeneic transfusions, thrombotic complications, outcomes, and monitoring of coagulation, fibrinolysis, and inflammation were also recorded. RESULTS: Tranexamic acid reduced total postoperative bleeding by 43% in patients undergoing on-pump coronary artery bypass grafting and by 27% in those undergoing off-pump coronary artery bypass grafting (P <.0001), with 80% reduction in bleeding exceeding 600 mL (P <.001), 58% reduction in the requirement for all allogeneic transfusions (P =.07), and no apparent effect on thrombotic complications or outcome. This was associated with a reduction in plasma D-dimer levels (P <.0001), to a greater degree in patients undergoing on-pump coronary artery bypass grafting (P <.0001), and interleukin 6 levels (P <.0001), to a greater degree in patients undergoing off-pump coronary artery bypass grafting (P <.001). CONCLUSIONS: By affecting fibrinolysis, tranexamic acid significantly reduces bleeding both in off- and on-pump coronary artery bypass grafting and may modulate inflammation in these surgical settings.

Aged↗

Outpatient treatment of microscopic and rim hyphemas in children with tranexamic acid.

Twenty-one patients aged 4 to 15 years with microscopic or rim hyphemas were treated as out-patients with systemic tranexamic acid therapy. The protocol included limited activity at home, topical steroid therapy, no dilating drops, patching for comfort or surface abrasions only, and follow-up every 24 to 48 hours. With this regimen no patient had a secondary hemorrhage. The incidence of associated injuries was surprisingly high, including four patients with angle recession, two with choroidal ruptures and four with commotio retinae, two of whom manifested retinal holes, requiring cryotherapy. We conclude that tranexamic acid therapy decreases the risk of secondary hemorrhage in ambulatory patients with hyphema, but careful assessment and follow-up are necessary to rule out associated ocular injury.

Administration, Oral↗

[Use of tranexamic acid for bleeding control in myocardial revascularization].

PURPOSE: To compare two groups of 80 patients undergoing to myocardial revascularization with the use of antifibrinolytic drug tranexamic acid and its efficacy in reduce bleeding and blood transfusion. METHODS: Prospective analysis of two groups of 80 patients. Group A-no antifibrinolytic therapy (dec 91-may 92) and group B-fibrinolytic therapy-tranexamic acid-10g EV (jun-dec/92). Quantification of mediastinal drainage over 12h as well as the blood or derivatives received at the same time. RESULTS: Hospital mortality: group A-3.8%, group B-2.5%. Drainage (12h): group A-602 +/- 547 ml and group B-260 +/- 260 ml (p < 0.001). Blood transfusion (12h): group A-1,782 +/- 1,163 ml and group B-1,105 +/- 839 ml (p < 0.001). COMPLICATIONS: group A-two cases of intraoperative myocardial infarction, one episode of jaundice; group B-one case of intraoperative MI, one reoperation for bleeding control, one episode of jaundice, one of renal insufficiency, two mediastinitis and one seizure. The mean hospitalization time was ten days in both groups. CONCLUSION: Tranexamic acid was an effective drug in bleeding control and in reducing blood transfusion in the postoperative of patients submitted to myocardial revascularization.

Adult↗

Tranexamic acid for the treatment of advanced ovarian carcinoma.

In the present phase II trial, 26 heavily pretreated patients with advanced recurrent ovarian carcinoma were treated with tranexamic acid, 4-6 g per os daily for at least 3 months. Of these 26 patients, 3 had stage IIb, 21 stage III and 2 stage IV. Histologic examination revealed serous adenocarcinoma in 13, mucinous in 3, endometroid in 4, 1 anaplastic and 5 unspecified adenocancer. Twenty of the tumors were poorly differentiated and 5 highly-moderately differentiated. No objective response was noted but all the highly-moderately differentiated tumors showed a stable disease state with a median duration of 6 months (range 4-36 months). The patients with poorly differentiated tumors had a median survival of 4 months. Most of the patients had some form of gastro-intestinal side effect. This investigation has shown that treatment with tranexamic acid was not particularly helpful in poorly differentiated cases in which modern combined chemotherapy already had failed. The effect in highly-moderately differentiated cases needs further evaluation.

Adenocarcinoma↗

Treatment of advanced ovarian cancer with fibrinolytic inhibitor (tranexamic acid).

A patient with inoperable advanced ovarian cancer with metastases and ascites who had received several courses of radiotherapy and chemotherapy is presented. On her 6th admission, therapy with the fibrinolytic inhibitor tranexamic acid was followed by arrest of ascites and tumor growth; then at exploratory laparotomy, examination of tumor cells revealed encapsulation of fibrinoid substance and proliferation of connective tissue. The patient, still receiving tranexamic acid, is now free from noteworthy symptoms.

Cyclohexanecarboxylic Acids↗

Traumatic hyphaema treated with the antifibrinolytic drug tranexamic acid.

During the year 1975 (Jan. 1st-Dec. 31st) 72 patients, consecutively admitted to the eye department of Arhus Kommunehospital with traumatic hyphaema, were treated with the antifibrinolytic drug tranexamic acid. Secondary haemorrhage occurred in one case. This incidence of secondary haemorrhage (1.4%) seems to be the lowest on record. A group of patients from the period 1965-1968, treated identically with the exception of the tranexamic acid, were selected for comparison. This group of 135 patients included 9 cases (6.7%) with a secondary haemorrhage. The difference between these two groups is statistically significant (P less than 0.05).

Adolescent↗

Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis.

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.

Animals↗