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The effect of Trasylol on the fibrin deposition and elimination in the lungs of rats with intravascular coagulation induced by thrombin or thromboplastin was studied quantitatively. Trasylol strongly reduced the precipitation of fibrin in the lungs after intravenous injection of thromboplastin, while the same effect was not obtained after injection of thrombin. The elimination of fibrin from the lungs was delayed after treatment with Trasylol. This effect was not observed in rats treated with a synthetic fibrinolysis inhibitor, tranexamic acid (AMCA), in addition to Trasylol.

The importance of the coagulation process in the renal functional changes was studied following a standardized, sublethal third degree thermal injury in rats covering 14% of the body surface. Immediately post-burn, the glomerular filtration rate, measured as clearance of PEG 1000, decreased to about one-third of the pre-burn value, which gradually was regained within 24 hours. No decrease in the TmPAH/GFR ratio, indicating impairment of the tubular secretory capacity, was found. The serum urea nitrogen level was moderately elevated 24 hours after the burn, but at later intervals normal values were found. Anticoagulation with heparin or fibrinolysis inhibition with tranexamic acid did not influence the results of the GFR, TmPAH or serum urea nitrogen measurements and therefore no causative connection was found between a coagulation process and the renal functional changes in this trauma model.

A double blind randomized trial was made to ascertain the effect of tranexamic acid (AMCA) (Cyklo-kapron®) on the postoperative blood loss after conization. The case material consisted of 50 women referred to the clinic because of dysplasia or non-invasive cancer of the cervix. Five patients were excluded for various reasons. The treatment started in the evening of the day of operation and was continued for another 12 days, the dose being three tablets every 8 hours, corresponding to 4.5 g of tranexamic acid daily when the active drug was given. During the first 7 postoperative days, when the patients were in hospital, the blood losses were determined quantitatively. Prophylactic treatment with tranexamic acid reduced the postoperative blood loss as compared with the placebo group, the blood losses being 23 ± 3.2 ml and 79 ± 20.4 ml respectively. Sudden profuse bleeding postoperatively, requiring remedial measures, occurred in 7 patients, all in the placebo group. With the exception of 1 patient in the pl...

In 10 children with Politano and Leadbetter's antireflux operation, tranexamic acid reduced the blood loss, especially postoperatively. In three patients renewed bleeding occurred when the treatment stopped. Antifibrinolytic treatment probably reduced the need for blood transfusions in these operations. In six children, however, large clots were passed with the urine from the fourth to the ninth day postoperatively, probably due to inhibition of the advantageous clot lysis.

Summary. A randomized controlled trial of the antifibrinolytic agent amino-methylcyclohexane carboxylic acid (AMCA, Tranexamic acid) in the prophylactic treatment of haemophilia is reported. The active treatment (2 g daily) or indistinguishable inert tablets were given for 12 consecutive periods of 28 days. The effect of the active treatment was minimal and incapacity from the disease and the need for the administration of factor VIII were not reduced. It is considered that sound evidence does not exist for recommending the prophylactic use of antifibrinolytic drugs in haemophilia.

Background: The antifibrinolytic drug tranexamic acid (TA) decreases blood loss in Pediatric patients under going cardiac Surgery. However its efficacy has not been extensively studied in children. Method: We examined 750 children under going cardiac surgery form 2004 to 2007 in National Institute of Cardiovascular Diseases (NICVD), 379 children in the Tranexamic Acid group (TA) and 371 included in placebo (P) group. After induction of anesthesia and prior to skin incision, patients received either tranexamic acid (10mg/kg followed by 1mg/kg/hr) and saline placebo. After admission to intensive care unit total blood loss and transfusion requirements during the first12 hours were recorded. Result: 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 (p

The hemostatic effect of Menaquinone-4 (K2) on bleeding at partially incised tail vein of rats pretreated with Dicumarol, Urokinase or Carbon Tetrachloride to prolong definitely bleeding time was studied. The effect of K2 on the bleeding was compared with the effects of Phytonadion (K1), Etamsylate, Tranexamic Acid (AMCHA), Epsilone Aminocaproic Acid (EACA) and Carbazochrome (CA-17). Intramuscularly administered K2, K1 and AMCHA showed statistically significant effect on shortening bleeding time on the rats given Dicumarol but K2 was the most potent. The bleeding time on K2-administered rats pretreated with Carbon Tetrachloride was significantly shortened, but K1 showed no effect. The bleeding time on the rats given Urokinase was apparently reduced by AMCHA, while K2 and K1 were not significantly effective.

A double blind experiment was performed to test the possible prophylactic effect of the antifibrinolytically active tranexamic acid (Cyklokapron ® ) on alveolitis sicca dolorosa ("dry socket"). Tablets containing tranexamic acid and placebo were administered orally at random selection for 5 days to 71 consecutive patients who had had an impacted mandibular third molar removed. In this investigation tranexamic acid did not seem to prevent alveolitis sicca dolorosa. The possible reasons for this are discussed.

The fibrinolytic activity in the N-butyl-N-butanol (4)-nitrosamine (BBN) induced bladder tumors in rats and normal rat bladders was investigated at cellular level by the histochemical fibrin slide technique, and the ratio of plasminogen activator and urokinase inhibitor contained in tissue was estimated by the fibrin plate method. The plasminogen activator activity in the bladder epithelium gradually decreased as the neoplastic process became established, and the cancer cells lost the fibrinolytic activity of the normal tissue from which they sprang. The ratio in the cancerous tissue was strikingly on the side of inhibitor (1:434) as compared with that in the normal tissue (1: 32). Concomitantly, a highly significant reduction of fibrinolytic activity in blood, assayed by euglobulin lysis time, was observed after the development of the carcinoma. It may be reasonable to assume that the ratio in the cancerous tissue serve for antiplasmin in the fibrinolytic system in blood. Antifibrinolysis induced with tranexamic acid had no significant effect on the incidence and growth of the bladder tumors.

Heart lymph flow increased three to ten times after infusion of thrombin in dogs in whom fibrinolysis had been inhibited, indicating an increased rate of fluid loss from the coronary microcirculation a few hours after the onset of intravascular coagulation. Aspartate aminotransferase (AAT=GOT) activity in heart lymph decreased after thrombin infusion, indicating that severe myocardial cell damage had not occurred within the first seven hours after thrombin infusion.

SummaryA double-blind cross-over study of the prophylactic value of tranexamic acid (“Cyklokapron”), in a dose of 3.0 g per day, against spontaneous bleeding episodes in severe haemophilia was undertaken. Records of bleeding episodes were maintained during therapy in twenty boys with confirmed clinical severity, over two school terms. A significant reduction (p

SummaryOral administration of tranexamic acid, in a dosage of 3 g daily from the first day of menstruation onwards, significantly decreases menstrual haemoglobin loss in women with so-called essential menorrhagia.The frequency of side-effects reported did not differ between “active” and “placebo” periods.

The new caseinolytic assay method for antiplasmin activity of synthetic compounds was established by introducing the determination of ID50. trans-Form isomer of 4-aminomethylcyclohexanecarboxylic acid (tranexamic acid) was shown to have very potent antiplasmin activity whereas the cis-form isomer was little effective. The antiplasmin activity of tranexamic acid was 5-7 times greater than that of e-aminocaproic acid.

A series of 215 menorrhagic women was treated with curettage, a uterus-contracting agent (methylergobaseinmaleate), ovulation inhibitors (combined contraceptive pills), and the antifibrinolytic agents epsilon aminocaproic acid (EACA) and tranexamic acid (AMCA). Another antifibrinolytic agent, paraaminomethyl-benzoic acid (PAMBA), was used in a small series comprised of 15 women. Curettage and methylergobaseinmaleate did not significantly reduce the menstrual blood loss. Ovulation inhibitors EACA and AMCA reduced the menstrual blood loss by about 50 per cent. PAMBA was used in too small a series for the evaluation of the optimal effect, but treatment with this drug also reduced the menstrual blood loss.

Treatment of menorrhagia with an antifibrinolytic agent tranexamic acid (AMCA) was investigated by double-blind trial and dose-response studies. 36 women aged 15-49 years were included in the study. The decrease in blood loss during AMCA treatment was statistically significant (.05 < p < .1). No difference was seen between the women with and those without fibroids. 17 of the women reported no side effects. 2 women had side effects only with the placebo and 6 did so on both regimens. In 7 women side effects occurred only with the high dosage. The main side effects were diarrhea and abdominal pains.

AMCA (tranexamic acid, Cyklokapron® KABI) was given intravenously according to the double blind technique to 92 non-selected patients who underwent transvesical prostatectomy. Treatment with both 3 g AMCA per day and 1.5 g per day resulted in a statistically significant reduction in post-operative bleeding. Already during the initial post-operative period when 70% of the total postoperative blood loss occurred, the reduction in bleeding was significant in the AMCA treated patient groups. Side effects were small and were reduceable still further if the preparation was administered slowly.

Summary Two operations upon a giant gluteal lymph-angioma in a boy were complicated by massive haemorrhage. The complication proved to be due to fibrinolysis stimulated by activators released by the tumour. The diagnosis was confirmed by the demonstration of high fibrino-lytic activity and FDP in blood and discharge drained from the wound. The bleeding was effectively controlled by AMCA (tranexamic acid, Cyclokapron®). Long-term treatment with AMCA was accompanied by further reduction in size of the lymphangioma.

The antifibrinolytic effect of tranexamic acid (trans-4-aminomethylcyclohexane-1-carboxylic acid, trans-AMCHA) was found to be markedly potentiated in the presence of human serum. This potentiation due to serum was mainly contributed by α2-macroglobulin antiplasmin. Using purified α2-macroglobulin antiplasmin, it was found that the potentiation of the inhibitory effect of trans-AMCHA on plasmin was observable only when fibrin was used as the substrate of plasmin; with fibrinogen or casein as the substrate such a potentiation was not observed. This phenomenon seems to be related to the clinical effectiveness of trans-AMCHA.

Antifibrinolytic premedication with tranexamic acid (Cyklokapron) was given to 30 rabbits before renal puncture. Renal angiography 1 week after puncture revealed only two arteriovenous fistulae. In a previous experimental szries kidney puncture under the same conditions, but without administration of Cyklokapron, resulted in 14 arteriovenous fistulae in 36 rabbits. The difference between these results is significant.The investigation indicates that antifibrinolytic premedication before renal biopsy may be of value in order to reduce the frequency of renal arteriovenous fistulae following renal biopsy, which have been found to be more common than formerly believed.

HEREDITARY angioneurotic edema results from an inborn error in the biosynthesis of a serum alpha-2 globulin that inhibits the enzymatic activity of the first component of complement and is thus des...

The pharmacokinetics of tranexamic acid has been investigated in two healthy volunteers. The behaviour of the drug can be described in terms of a two compartment open model; the disposition (biological) half-life was 2.7 h and 1.9 h, respectively. In five normal volunteers the mean total recovery in urine 48 h after dosing was 94.8%. The renal clearance in the two subjects, adjusted to 1.73 m2 body surface area, was 135 and 132 ml/min/1.73 m2, respectively, indicating that tranexamic acid is eliminated by glomerular filtration and that neither tubular excretion nor absorption takes place.

Severe liver disease is frequently associated with a bleeding tendency and/or abnormalities in the laboratory tests of hemostasis. The latter comprise deficiencies of one or more of the coagulation factors II, V, VII, IX, X, XI, and XIII, thrombocytopenia and/or thrombocytopathia, and increased fibrinolytic activity in the plasma.

Ratten wurden mit hohen Dosen des Fibrinolyseinhibitors Tranexamsaure gefuttert. Die fibrinolytische Aktivitat der grossen Herzgefasse und der Coronargefasse wurde histochemisch untersucht und mit einer Kontrollgruppe verglichen, wobei sich ergab, dass der Gehalt der Gefasswande an Fibrinolyseaktivatoren durch die Tranexamsaure nicht beeinflusst wurde.

Bleeding after dental extraction was controlled with tranexamic acid in 19 patients with haemophilia and 3 with Christmas disease. The results were slightly better than those obtained with aminocaproic acid; the dose used was smaller; and side effects were few.

In a double-blind trial tranexamic acid (Cyclokapron) 1 g. four times a day for the first four days of menstruation, significantly decreased menstrual blood loss in women with menorrhagia for which no organic cause had been found. No difference in side-effects was noted between the active and placebo treatment.

In 4 patients with subarachnoid haemorrhage after ruptured intracranial aneurysm, tranexamic acid (AMCA) was used to prevent the recurrence of the bleeding. 1000 mg of AMCA was given intravenously 6 times a day for 8 days. The fibrinolytic activity of blood and spinal fluid was measured simultaneously with the etermination of AMCA levels before and after the beginning of treatment. The fibrin plate method showed no fibrinolytic activity in plasma or in CSF. Local fibriolysis was demonstrated by the presence of fibrin degradation products in spinal fluid. After repeated administration, AMCA crossed the blood-brain barrier and effectively inhibited the local fibrinolysis within the spinal fluid. The findings in this study suggest that in patients with subarachnoid haemorrhage AMCA should be aministrated intravenously in a dosage of 15–20 mg/kg body weight 6 times a day as soon as possible after the bleeding. But treatment with the antifibrinolytic drug does not change the indication for surgical therapy.

The symptomatic therapy of hereditary angioneurotic edema with tranexamic acid and suramin in two patients is reported. The first patient responded well to tranexamic acid (Cyclocapron®) but not to suramin. In the second patient, attacks of edema could apparently be better prevented with suramin.

(1973). Effect of Tranexamic Acid (CyklokapronR) on the Synthesis of Chondroitin Sulphate and the Content of Hexosamine in the Same Fraction on Normal and Degenerated Joint Cartilage in the Rabbit. Acta Orthopaedica Scandinavica: Vol. 44, No. 3, pp. 249-255.

Summary The metabolism of human fibrinogen, labelled with radioactive iodine, was studied in 35 healthy subjects over a 5 yr period using eight fibrinogen preparations in 23 labelling procedures. The labelled fibrinogen was highly clottable and homogeneous on agarose gel filtration, immunoelectrophoresis and auto-radiography. Results in the control subjects were: plasma volume 42 ± 7 ml/kg; plasma fibrinogen concentration 284 ± 71 mg/100 ml; total plasma fibrinogen pool 119 ± 40 mg/kg, representing 0.72 ± 0.07 of the total body pool; fibrinogen half-life 4.14 ± 0.56 days; fractional catabolic rate 0.24 ± 0.04 of the plasma pool/day; fractional transcapillary efflux rate 0.60 ± 0.26 of the plasma pool/day. Comparable results were obtained for all labelled fibrinogen batches. Anticoagulation with heparin in five control subjects had no influence on the fibrinogen half-life. Inhibition of the fibrinolytic system with tranexamic acid in five control subjects had no influence on the fibrinogen half-life in four of them but resulted in a prolongation in one subject. A mathematical compartmental model for the metabolism of fibrinogen is proposed, consisting of one extra vascular compartment and three catabolic pathways (basic protein turnover, intravascular fibrin formation, and intravascular fibrino(geno)lysis). In physiological conditions intravascular fibrin formation or fibrino(geno)lysis are not essential in the fibrinogen turnover.

The role of tranexamic acid in the control of post-extraction haemorrhage in patients with clotting defects is discussed. This drug appears to have certain advantages over epsilon amino caproic acid. The results of a retrospective study carried out on 19 patients with clotting disorders of varying degrees of severity, some of whom received tranexamic acid, are presented. A regime is suggested for the management of patients with clotting defects, using tranexamic acid.

In a double-blind trial in patients with bleeding from the upper gastrointestinal tract, those whose source of bleeding was distal to the gastro-œsophageal junction and whose barium-meal examination was negative benefited from oral tranexamic acid ('Cyclokapron') (1·5 g., eight-hourly). The volume of blood required for retransfusion was less in the treated group, especially in those patients with a negative barium-meal examination. These findings are compatible with the concept of a fibrinolytic component in upper gastrointestinal bleeding, which may be of particular importance when bleeding is due to acute superficial erosions.