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PubMed2002

Comparative evaluation of some new tranexamic acid derivatives and their copper (II) complexes for antitumor, analgesic, bactericidal and fungicidal activities.

The objective of this series of investigation was the synthesis and comparative evaluation of biological and pharmacological activities of some substitutive derivatives of Tranexamic Acid (T.A) and their copper (II) complexes. N-Phthaloyltranexamic Acid (A-1), N-Acetyltranexamic Acid (A-2), Di-Tranexamate Diaquo Copper (II) (C-1) Di-N-Phthaloyltranexamate Diaquo Copper (II) (C-2) and Di-N-Acetyltranexamate Diaquo Copper (II) (C-3) were synthesized, using novel and reproducible procedures. These compounds were characterized by exploiting techniques such as FTIR, Mass Spectroscopy and FT 1H NMR. Bioactivities of the compounds were carried out and it was found that these compounds exhibited excellent anti-tumor, significant analgesic and antifungal activities.

Journal Article↗

PubMed1984

Effects of tranexamic acid and local fibrin deposition of fibrinolysis and granulation tissue formation in preformed cavities.

The effects of locally deposited fibrin and of tranexamic acid-induced antifibrinolysis on forming granulation tissue were studied in the light of a recently developed method for treatment of postoperative fistulas by occlusion with a fibrin clot. Perforated teflon cylinders, either empty or fibrin-filled, were implanted subcutaneously in rats and extracted after 2 weeks. Fibrin deposition was found to stimulate granulation tissue ingrowth into the cylinders but it did not change the fibrinolytic activity in the granulation tissue. A significantly higher fibrinolytic activity was, however, found in the tissue fluid collected from the space between the granulation tissue and the implanted fibrin clot compared to tissue fluid from cylinders implanted empty. Tranexamic acid significantly reduced the fibrinolytic activity on the granulation tissue and delayed lysis of the implanted fibrin clot. It also reduced granulation tissue ingrowth but it did not abolish the positive effects of the clot on granulation tissue formation.

Animals↗

PubMed2003

Effect of tranexamic acid incorporated in fibrin sealant clots on the cell behavior of neuronal and nonneuronal cells.

Fibrin sealants are commonly used for hemostasis following surgery on various types of tissues. Aprotinin, an effective fibrinolysis inhibitor, is one of the components in some fibrin sealant products currently available. Tranexamic acid (tAMCHA) is another fibrinolysis inhibitor and is used as an alternative to aprotinin. Recent studies on fibrin sealant products containing tAMCHA indicate that it may be responsible for various adverse reactions when used in neurological applications. To determine a possible mechanism for such adverse reactions, we examined the effect of tAMCHA on the behavior of neuronal and nonneuronal cells using in vitro assays. The data indicate that different concentrations of tAMCHA incorporated in fibrin clots had no effect on the initial cell adhesion of either proliferative cells (glial cells and fibroblasts) or nonproliferative cells (neuronal cells) to the fibrin clots. Moreover, a high concentration of tAMCHA (300-450 mM) incorporated in the fibrin clots increased glial and fibroblast proliferation on fibrin clots. However, because tAMCHA is known to leach out of the fibrin clots, we have also examined the effect of solubilized tAMCHA in a growth medium on cells seeded on matrix-coated surfaces. A high concentration (300-450 mM) of tAMCHA detached all cell types from matrix-coated dishes. Our model suggests that tAMCHA in fibrin clots has no adverse effect on cells bound to the fibrin clots; however, tAMCHA leaching out from the fibrin clots reduces adhesion of adjacent cells bound to their natural extracellular matrix. Thus, a high concentration of tAMCHA should not be used as a fibrinolysis inhibitor in fibrin sealant products, especially in neurosurgery.

Cell Adhesion↗

PubMed1980

Preoperative treatment of ruptured intracranial aneurysms with tranexamic acid and monitoring of fibrinolytic activity.

The fibrinolytic activity in cerebrospinal fluid has been monitored by determination of levels of fibrin split products (FSP) in 23 patients with ruptured intracranial aneurysms. In 20 of these 23, FSP was found in the cerebrospinal fluid (CSF), with levels ranging from 10 to 80 micrograms/ml. Eleven of the 23 patients were treated with 2 gm tranexamic acid daily. In these patients FSP was found in only two cases during the 2nd week, while in 12 untreated patients it was found in 10 cases. These results suggest that there exists a localized fibrinolytic activity, and monitoring the FSP levels in the CSF may be a simple and accurate method for controlling the efficiency of antifibrinolytic therapy. Thus, treatment could be begun with a lower dose, which could be increased later as deemed necessary from the results of careful monitoring.

Aminocaproic Acid↗

PubMed2004

Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid.

OBJECTIVE: We examined the role of coagulation and fibrinolysis in lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats, studying their contribution to fibrin deposition and organ failure in rats with LPS-induced DIC by concurrent administration of low molecular weight heparin (LMWH) with or without tranexamic acid (TA). METHODS: DIC was induced in male Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In the LPS+LMWH group LMWH (200 u/kg) was administered to rats from 30 min before the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 microg/kg) and TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS for 4.5 h. RESULTS: In the LPS+LMWH group lower plasma levels of TAT, D dimer, creatinine, and alanine aminotransferase were observed, along with less glomerular fibrin deposition and improved survival over rats administered LPS alone. However, these effects of LMWH were completely eliminated and damage beyond that observed in rats administered LPS alone resulted from combined administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels remained lower than in the group administered LPS alone. CONCLUSIONS: Suppression of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased organ damage in this study, suggesting that depressed fibrinolysis plays a large role in organ failure resulting from LPS-induced DIC, even though hemostatic activation is moderately suppressed by LMWH.

Animals↗

PubMed1979

Spontaneous thrombosis of ruptured intracranial aneurysms during treatment with tranexamic acid (AMCA). Report of three cases.

Radiographically verified spontaneous disappearance of medium-sized arterial cerebral aneurysms is seldom reported, and only three times in connection with antifibrinolytic therapy (EACA). In our clinic repeat angiograms have shown non-filling of the aneurysms in three patients during treatment with tranexamic acid (AMCA) two, three, and four weeks respectively after primary bleeds. Initially, all three patients had severe radiological vasospasm associated with neurological deterioration. Follow-up angiograms have demonstrated partial reappearance of the aneurysm after one month in one patient and complete disappearance of the aneurysms in the other two patients after 9 and 22 months respectively. In two cases occlusion of cerebral arteries occurred. With regard to the higher risk of severe vasospasm and occlusion of cerebral arteries in our opinion it should not be a therapeutic goal to try to achieve a thrombosis of a ruptured aneurysm with antifibrinolytic drugs. The reason for spontaneous aneurysm thrombosis during treatment with AMCA may be a local inhibition of plasminogen activators in and around the aneurysm wall. It may also be related to the sympathomimetic property of the drug, with vasospasm and a subsequent flow-reduction inside the aneurysm or a possible interaction with other drugs and substances.

Adult↗

PubMed1992

Cerebral blood flow in patients with a subarachnoid haemorrhage during treatment with tranexamic acid.

Many clinicians currently use antifibrinolytic therapy (AFT) routinely in the management of subarachnoid haemorrhage (SAH). Many others do not, either because they remain unconvinced that AFT reduces the risk of rebleeding, or that the medication itself causes serious complications and in particular cerebral ischaemia. Nineteen randomly selected patients were studied, 9 receiving tranexamic acid (9 g a day) and the remaining 10 placebo, with SAH confirmed by CT scanning and by lumbar puncture. There was no difference between the active and placebo group regarding the age, sex, clinical grade, CT scan and angiographic appearance. The intravenous Xe133 technique was used for serial determinations of hemispheral cerebral blood flow. The cerebral blood flow remained stable during the first week following subarachnoid haemorrhage, and then fell progressively, reaching its bottom level by the end of the second week. The cerebral blood flow levelled out during the third week at the end of which a sharp elevation, well above the first week's post-subarachnoid haemorrhage level, was noted. This rebound rise of cerebral blood flow was observed for both cerebral hemispheres. Cerebral flow was greatest in the contralateral (to side of ruptured aneurysm) brain hemisphere save for the peak observed during the first week post-subarachnoid haemorrhage. The difference between the ipsi- and contralateral hemispheres was most pronounced in patients receiving active treatment. Analysis of variance showed that cerebral blood flow was reduced by the active treatment and especially more so on the ipsilateral side with the ruptured aneurysm. The usefulness of AFT should therefore be reconsidered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

[Endoscopic hemostasis in hemorrhagic peptic ulcer. A review and pilot study of local thrombin injection combined with systemic fibrinolysis inhibition (with tranexamic acid)].

Today, most upper GI-haemorrhages can be handled without surgery. We discuss the available endoscopic haemostatic methods. Injection therapy seems to be as effective as laser-, heater probe- and bipolar electrocoagulation, and is often preferred because the equipment is inexpensive. In a pilot study of 37 patients with haemorrhage from peptic ulcer (13 with active bleeding and 24 with stigmata of recent hemorrhage) we injected thrombin in the ulcer base and treated the patients systemically with an antifibrinolytic drug (tranexamic acid) for five days. Endoscopic follow-up revealed stigmata of recent haemorrhage in 23 patients on day 1 and in eight patients on day 5. "Blood in stomach" was seen in eight patients on day 1 and in two patients on day 5. Four patients had clinical signs of rebleeding, but only one of them needed operation (definite hemostasis 97%). There were no obvious side effects of the treatment. Contrary to other endoscopic methods, local injection of thrombin does not damage the normal mucosa. However, the method has not been sufficiently explored as yet, and cannot be recommended without strict control and follow-up measures. Early control endoscopy seems to be a sensitive way of monitoring haemostasis.

Cyclohexanecarboxylic Acids↗

PubMed2005

Tranexamic acid reduces allogeneic red cell transfusions in patients undergoing total knee arthroplasty: results of a meta-analysis of randomized controlled trials.

BACKGROUND: The delayed bleeding associated with total knee arthroplasty (TKA) may be a result of a tourniquet-induced imbalance of the procoagulant and fibrinolytic systems. There are conflicting results in the literature about tranexamic acid (TA) infusion in reducing postoperative blood loss and the number of transfused red cells (RBC) units. A meta-analysis was performed to summarize the results of different research studies. STUDY DESIGN AND METHODS: Randomized controlled trials reported through October 2004 were retrieved, and nine studies met the criteria for meta-analysis. Summary odds ratio (OR) of allogeneic transfusion and a weighted mean difference (WMD) of transfusions per patient in TA-treated group versus placebo group were calculated across studies. RESULTS: The use of TA significantly reduced the proportion of patients requiring blood transfusion (summary OR, 0.10; 95% CI, 0.06-0.18; p < 0.00001) and the number of RBC transfusions per patient (WMD, -1.72; 95% CI, -2.11 to -1.33; p < 0.00001) when compared with patients who received placebo. CONCLUSION: Our meta-analysis shows that the use of TA for patients undergoing TKA is effective in reducing the requirements of allogeneic blood transfusion.

Antifibrinolytic Agents↗

PubMed1997

Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty.

The application of a pneumatic tourniquet in orthopedic procedures enhances local fibrinolysis. Consequently, a short-term antifibrinolytic therapy may be indicated in this clinical situation to reduce postoperative blood loss. The purpose of this prospective double-blind study was to investigate the effect of tranexamic acid (TA) on blood loss associated with total knee arthroplasty (TKA). Seventy-five patients scheduled for 77 TKAs were randomized to receive either TA (n = 39) or equal volume of normal saline (NS, n = 38). Before deflation of the tourniquet, 15 mg/kg of TA was given intravenously followed by two 10-mg/kg additional doses. Perioperative blood loss gathered in surgical gauzes, suction reservoirs, and postoperative drainage system was measured. The number of transfusions given during hospitalization was registered. Total blood loss (mean +/- SD) was 689 +/- 289 mL in the TA group and 1509 +/- 643 mL in the NS group (P < 0.0001). The mean number of transfused red cell units in the TA group was 1.0 +/- 1.2 compared to 3.1 +/- 1.6 in the NS group (P < 0.0001). Twenty-two patients in the TA group and four patients in the NS group were treated without transfusion (P < 0.00003). Two patients in the TA group and three in the NS group had a deep venous thrombosis, including a fatal case of pulmonary embolism in the NS group. We conclude that short-term TA therapy significantly reduces TKA-associated blood loss and transfusion requirements without increasing thromboembolic complications.

Aged↗

PubMed2006

Localized intradermal microinjection of tranexamic acid for treatment of melasma in Asian patients: a preliminary clinical trial.

BACKGROUND: Melasma is a common cosmetic problem among Asians. While various treatments are currently being used, there is no entirely satisfactory treatment. It was recently reported that the topical plasmin inhibitor is an effective treatment for ultraviolet-induced hyperpigmentation. OBJECTIVE: Because there are no studies assessing the efficacy and safety of localized microinjection of tranexamic acid (TA) for the treatment of melasma, we conducted a pilot study to evaluate the efficacy and side effects of this potentially new method for the treatment of melasma in Korean women. METHODS: A total of 100 women with melasma, after written consent, were enrolled for a prospective open pilot study of 12 weeks. After applying topical anesthesia, 0.05 mL TA (4 mg/mL) was injected intradermally into the melasma lesion at 1 cm intervals by using a 0.5 mL insulin syringe with a 30-gauge needle. This was repeated weekly for 12 weeks. A clinical investigator evaluated the results by using the Melasma Area and Severity Index (MASI) at baseline and at 4, 8, and 12 weeks. The patient satisfaction questionnaire was documented at 12 weeks. Safety evaluations were performed at each follow-up visit. RESULTS: Eighty-five patients completed the trial. A significant decrease in the MASI from baseline to 8 and 12 weeks was observed (13.22+/-3.02 vs 9.02+/-2.62 at week 8 and vs. 7.57+/-2.54 at week 12; p<.05 for both). The patients' self-assessment of melasma improvement was as follows: 8 of 85 patients (9.4%) rated as good (51-75% lightening), 65 patients (76.5%) as fair (26-50% lightening), and 12 patients (14.1%) as poor (0-25% lightening). Side effects were minimal and all the patients tolerated the treatment well. CONCLUSION: Based on these results, we suggest that the intralesional localized microinjection of TA acid can be used as a potentially new, effective, and safe therapeutic modality for the treatment of melasma.

Adult↗

PubMed2006

Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial.

BACKGROUND: Risks and costs of allogeneic blood transfusions mandate strategies to reduce blood loss in surgery. The objective of this study was to assess the efficacy of antifibrinolytic treatment in reducing perioperative blood loss during total knee replacement. METHODS: A double-blind, randomized and placebo-controlled clinical trial was carried out on 127 patients undergoing total knee replacement. Patients in the study group received tranexamic acid 10 mg kg(-1) i.v. just before the tourniquet was deflated and 3 h later, or epsilon-aminocaproic acid 100 mg kg(-1) before tourniquet deflation followed by continuous perfusion (1 g h(-1)) during 3 h. External perioperative blood loss was measured and total blood loss was calculated. The number of patients transfused and number of packed red cell (PRC) units transfused was recorded and possible postoperative thromboembolic complications were investigated. RESULTS: Total blood loss [mean (sd)] was 1099 ml (535) in the group that received antifibrinolytic agents and 1784 ml (660) in the control group (P<0.001). Five patients (7.5%) in the study group and 23 (38.3%) in the control group (P<0.001) received blood transfusions; the first group received a mean of 0.10 PRC unit per patient and the second, 0.58 (P<0.001). Mean reduction in haemoglobin levels (g dl(-1)) between preoperative and fifth day postoperative readings was 2.5 (0.9) in the study group and 3.4 (1.2) in the control group (P<0.001). Clinical assessment did not reveal any thromboembolic complications. CONCLUSIONS: Antifibrinolytic agents produce a significant decrease in blood loss in patients undergoing total knee replacement, reflected in a reduction in the number of blood transfusions required.

Aged↗

PubMed1998

Successful treatment of bleeding from colonic angiodysplasias with tranexamic acid in a hemodialysis patient.

Colonic angiodysplasias are a common source of gastrointestinal bleeding in patients with end-stage renal disease (ESRD). It is well known that bleeding from angiodysplasias can be a difficult therapeutic problem. This report describes a hemodialysis patient who suffered acute (massive) and chronic gastrointestinal bleeding from colonic angiodysplasias. Because endoscopic ablation could not be performed and resection of the colon was refused, pharmacological treatment with the antifibrinolytic agent tranexamic acid was attempted. A successful management of both the acute and chronic bleeding was achieved. No complications in terms of arterial or venous thrombosis were observed.

Angiodysplasia↗

PubMed2007

Comparison of structure, strength and cytocompatibility of a fibrin matrix supplemented either with tranexamic acid or aprotinin.

Fibrin sealants are used as hemostats, sealants, tissue adhesives, and as matrix for substances/cells in a number of surgical and tissue engineering procedures. Main characteristics of fibrin are high tensile strength, adhesive strength, biocompatibility, and resorption. A major adverse event would be premature fibrin lysis and recurrent bleeding. This must be prevented by fibrinolysis inhibitors. The most common fibrinolysis inhibitors used are aprotinin and tranexamic acid (t-AMCA). Comparison of commercially available fibrin sealants utilizing aprotinin or t-AMCA revealed a lower sealing efficacy in an in vivo lung resection model for a t-AMCA containing product. Therefore, we compared the influence of t-AMCA and aprotinin on structure, mechanical properties, and cytocompatibility of a fibrin matrix. In our experiments, we found that substitution of aprotinin with t-AMCA reduced the tensile strength and formation of fibrin fibers and affected viability of a fibroblast cell-line. In conclusion, t-AMCA negatively affects physical and biological properties of fibrin relevant for clinical application as well as tissue regeneration.

Animals↗

PubMed1999

Tranexamic acid inhibits fibrinolysis, shortens the bleeding time and improves platelet function in patients with chronic renal failure.

BACKGROUND: A defect in platelet function is the main determinant of the prolonged bleeding time in chronic renal failure (CRF). We previously reported a significant correlation between platelet abnormalities and elevated plasma markers of plasmin and thrombin generation. Our aim was to explore the effect of inhibiting both plasmin action with tranexamic acid (TA) and thrombin production with low molecular weight heparin (LMWH), on the bleeding time (BT) and platelet function in patients with CRF. METHODS: 37 patients with CRF (mean creatinine 8.6 +/- 4.4 mg/dl) under conservative treatment, with prolonged BT, entered this study and received TA during 6 days, with (n = 24) and without LMWH (n = 13). BT, platelet aggregation/secretion, platelet granule contents, von Willebrand factor and parameters of coagulation and fibrinolysis were recorded before and at the end of treatment. RESULTS: The BT was shortened in 26/37 (67%) patients. This effect was associated with significant improvement of platelet aggregation and secretion, with decrease to a normal range of fibrin/fibrinogen degradation products, mild increase in plasmin-antiplasmin complexes and pronounced reduction of circulating plasminogen. No differences were seen among patients with or without LMWH. No serious side effects or complications were observed. INTERPRETATION: These findings indicate that the activation of fibrinolysis plays a significant role in the defect of primary hemostasis in patients with CRF. Inhibition of plasmin activity with TA shortens the BT and improves platelet function in the majority of patients with severe disease.

Antifibrinolytic Agents↗

PubMed2006

Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a "blood transfusion"-free hepatectomy.

OBJECTIVE: To examine the feasibility of a real "blood transfusion"-free hepatectomy in a large group of patients with liver tumors. SUMMARY BACKGROUND DATA: Bleeding control and blood transfusion remains problematic in liver resection. A real "blood transfusion"-free hepatectomy in a large group of patients has rarely been reported. The impact of tranexamic acid (TA), an antifibrinolytic agent, on blood transfusion in liver resection is unknown. METHODS: A prospective double-blind randomized trial was performed on elective liver tumor resections. In group A, TA 500 mg was intravenously administered just before operation followed by 250 mg, every 6 hours, for 3 days. In group B, only placebo was given. The patients' background, blood transfusion rates, and early postoperative results in the 2 groups were compared. Factors that influenced blood requirement were analyzed. RESULTS: There were 108 hepatectomies in group A and 106 hepatectomies in group B. The patients' backgrounds, operative procedures, and hepatectomy extent did not significantly differ between the 2 groups. Although the differences of the operative morbidity and postoperative stay were not significant, a significantly lower amount of operative blood loss, lower blood transfusion rate, shorter operative time, and lower hospital costs were found in group A patients. No patient in group A received blood transfusion. No hospital mortality occurred in either group. Tumor size and use of TA were independent factors that influenced blood transfusion. CONCLUSIONS: Perioperative parenteral use of TA reduced the amount of operative blood loss and the need for blood transfusion in elective liver tumor resection. A real "blood transfusion"-free hepatectomy may be feasible with the assistance of parenteral TA.

Aged↗

PubMed2005

Kasabach-Merritt syndrome associated with giant liver hemangioma: the effect of combined therapy with danaparoid sodium and tranexamic acid.

n patients with Kasabach-Merritt syndrome (KMS), local activation of coagulation commonly results in disseminated intravascular coagulation (DIC). Progress of DIC is associated with 30-40% mortality as a result of uncontrollable hemorrhage. A 39-year-old woman with an enlarging giant liver hemangioma was diagnosed as having KMS with DIC. To control the hemorrhagic diathesis, we commenced combination therapy for DIC with danaparoid (1,250 Ux2/day, intravenously (IV)) and tranexamic acid (0.5 g x 3/day, peros (PO). Rapid improvement of the bleeding tendency and coagulopathy occurred in response to this treatment - that is, DIC was controlled without removing the giant hemangioma. The therapy did not restrict the behavior of the patient by continuous drip and angiography could be performed without bleeding. Such therapy may be beneficial in chronic DIC with activation of fibrinolysis.

Adult↗

PubMed1995

Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation.

OBJECTIVE: Activation of fibrinolysis is implicated in the development of vascular injury in certain lung injuries. It has yet to be reported that activation of plasmin is involved in extravasation caused by oleic acid (OA). We examined whether or not plasmin is involved in pulmonary extravasation by OA. DESIGN: Prospective trial. SETTING: University laboratory. SUBJECTS: A total of 78 guinea pigs (498.9 +/- 10.6 g). INTERVENTIONS: Evans blue (EB) was administered to anesthetized guinea pigs. Subsequently four protocols were followed: (1) After 1 min, 60 micro l/kg of OA was injected. Perfusion was performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2) After 1 min, 15, 30 or 60 micro l/kg of OA was injected. (3) Tranexamic acid (TA) (2 g/kg) or saline was administered 30 min before OA (15 micro l/kg) injection. (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min before OA (15 micro l/kg) injection. MEASUREMENT AND RESULTS: Except in protocol 1, the chest cavity was opened 90 min after OA injection. Perfusion was then performed. Airway was separated into four parts from trachea to distal bronchus. EB was extracted from the tissues and measured. OA caused an extravasation throughout airways in a time- and dose-dependent manner. Extravasation was more conspicuous in peripheral tissues. TA significantly attenuated extravasation, while diphenhydramine hydrochloride did not. CONCLUSIONS: It is suggested that plasmin, but not histamine, is involved in extravasation by OA. Inhibition of plasmin can be an effective strategy for treatment of this kind of lung injury.

Analysis of Variance↗