Antifibrinolytic Agent Tranexamic Acid Research Articles

Tranexamic Acid Within 4.5 Hours of Intracerebral Hemorrhage With the CTA Spot Sign: Systematic Review and Individual Patient Meta-analysis.

The antifibrinolytic agent tranexamic acid has been tested in intracerebral hemorrhage trials with overall neutral results. Ongoing contrast extravasation on CT angiography (spot sign) can identify individuals with ongoing bleeding who may benefit from anti-fibrinolytic therapy. We aimed to investigate the effect of tranexamic acid on hematoma growth in patients with spot signs treated within 4.5 hours of onset. We conducted a systematic review and individual patient meta-analysis, which we report according to the Preferred Reporting Items for Systematic Review and Meta-analyses of Individual Participant Data guidelines. PubMed and Embase were searched from inception to May 29, 2023, using the terms ((stroke) AND (randomised OR randomized) AND (tranexamic acid) AND (haemorrhage OR hemorrhage)). We included randomized trials comparing tranexamic acid with placebo in participants with primary intracerebral hemorrhage who had a spot sign and who had follow-up imaging within the required timeframe. Individual patient data were provided by each study and were integrated by the coordinating center. Data were pooled using a random-effects model. The primary endpoint was hematoma growth within 24 hours, defined as ≥33% relative or ≥6 mL absolute hematoma expansion compared with baseline, analyzed using mixed-effects-modified Poisson regression with robust standard errors, adjusted for baseline hematoma volume. Safety outcomes were mortality and major thromboembolic events within 90 days. Of 197 studies identified, 3 were eligible, contributing 162 participants for the primary analysis (60 female and 102 male). Hematoma growth occurred in 36 of 74 (49%) participants treated with tranexamic acid, compared with 48 of 88 (55%) participants treated with placebo (adjusted risk ratio 0.86, 95% CI 0.84-0.89, p < 0.001). Adjusted median absolute hematoma growth was 1.60 mL (95% CI 0.77-2.43) lower with tranexamic acid vs placebo. No differences in functional outcome or safety were observed. Tranexamic acid modestly reduced hematoma growth in patients with CT angiography spot signs treated within 4.5 hours of onset. Given the trials in the meta-analysis were individually neutral, these results require further validation before clinical application.

Anti-fibrinolytics for mucosal bleeding in adults with life-limiting illnesses: a systematic review

IntroductionPatients with life-limiting illnesses are at increased risk of mucosal bleeding. Usual management includes anticipatory planning and sedation, alongside anti-fibrinolytics, despite a lack of evidence for their use. Anti-fibrinolytic agents...

Systemic Tranexamic Acid for Reduced Postoperative Blood Loss and Less Bleeding Complications in Fleur-de-lis Abdominoplasty and Apronectomy.

Strategies minimizing surgical bleeding, including the antifibrinolytic agent tranexamic acid, play a crucial role in clinical practice to optimize overall surgical outcomes. Despite its proven efficacy in various clinical fields, there is a limited understanding regarding the use of tranexamic acid in plastic and aesthetic procedures. This study is the first investigating the effects of systemically administered tranexamic acid on postoperative blood loss and bleeding complications in fleur-de-lis abdominoplasties and apronectomies. Patients who received 1g tranexamic acid (n = 44) during fleur-de-lis abdominoplasty or apronectomy were retrospectively compared with those who did not (n = 44). In this context, the outcome parameters 24-h and total drain fluid production, drain time, hospital stay, absolute and relative drop in hemoglobin and hematocrit level as well as bleeding complications such as blood transfusion, hematoma puncture and evacuation were evaluated. Tranexamic acid significantly decreased both drainage volume in 24h (40.5%, p = 0.0046) and total drain fluid production (42.5%, p = 0.0017). Moreover, a shorter drainage time (19.4%, p = 0.0028) and hospital stay (21.4%, p = 0.0009) were observed. The administration of tranexamic acid was also associated with a reduced postoperative decline in hemoglobin and hematocrit levels. Notably, no bleeding complications were observed in patients who received tranexamic acid, while 6 events occurred in patients without (p = 0.0262). Systemic administration of tranexamic acid effectively reduced postoperative blood loss and bleeding complications in fleur-de-lis abdominoplasties and apronectomies. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Salts of S-(+)-Ibuprofen Formed via Its Reaction with the Antifibrinolytic Agents Aminocaproic Acid and Tranexamic Acid: Synthesis and Characterization

The paucity of multi-component compounds containing the non-steroidal anti-inflammatory drug (NSAID) S-(+)-ibuprofen (S-IBU) in combination with other drugs prompted the present study, which describes 1:1 salts of this active pharmaceutical ingredient (API) with the two most widely used antifibrinolytic APIs, namely 6-aminohexanoic acid (aminocaproic acid, ACA) and tranexamic acid (TXA), which are zwitterions in the solid state. Since NSAIDs are known to cause adverse side effects such as gastrointestinal ulceration, the presence of ACA and TXA in the salts with S-(+)-ibuprofen might counter these effects via their ability to prevent excessive bleeding. The salts were prepared by both the liquid-assisted grinding method and co-precipitation and were characterized by X-ray powder diffraction and single-crystal X-ray diffraction, thermal analysis, Fourier transform infrared spectroscopy, and solubility measurements. The X-ray analyses revealed a high degree of isostructurality, both at the level of their respective asymmetric units and in their extended crystal structures, with charge-assisted hydrogen bonds of the type N-H+⋅⋅⋅O− and O-H+⋅⋅⋅O− featuring prominently. The thermal analysis indicated that both salts had significantly higher thermal stability than S-(+)-ibuprofen. Solubility measurements in a simulated biological medium showed insignificant changes in the solubility of S-(+)-ibuprofen when tested in the form of the salts (S-IBU)−(ACA)+ and (S-IBU)−(TXA)+.

Anti-fibrinolytic agent tranexamic acid suppresses the endotoxin-induced expression of Tnfα and Il1α genes in a plasmin-independent manner.

Tranexamic acid (TXA) is widely used as an antifibrinolytic agent in hemorrhagic trauma patients. The beneficial effects of TXA exceed the suppression of blood loss and include the ability to decrease inflammation and edema. We found that TXA suppresses the release of mitochondrial DNA and enhances mitochondrial respiration. These results allude that TXA could operate through plasmin-independent mechanisms. To address this hypothesis, we compared the effects of TXA on lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines in plasminogen (Plg) null and Plg heterozygous mice. Plg null and Plg heterozygous mice were injected with LPS and TXA or LPS only. Four hours later, mice were sacrificed and total RNA was prepared from livers and hearts. Real time quantitative polymerase chain reaction with specific primers was used to assess the effects of LPS and TXA on the expression of pro-inflammatory cytokines. LPS enhanced the expression of Tnfα in the livers and hearts of recipient mice. The co-injection of TXA significantly decreased the effect of LPS both in Plg null and heterozygous mice. A similar trend was observed with LPS-induced Il1α expression in hearts and livers. The effects of TXA on the endotoxin-stimulated expression of Tnfα and Il1α in mice do not depend on the inhibition of plasmin generation. These results indicate that TXA has other biologically important target(s) besides plasminogen/plasmin. Fully understanding the molecular mechanisms behind the extensive beneficial effects of TXA and future identification of its targets may lead to improvement in the use of TXA in trauma, cardiac, and orthopedic surgical patients.

SEE Question

Article| September 2022 SEE Question ASA Monitor September 2022, Vol. 86, 11. https://doi.org/10.1097/01.ASM.0000874208.64950.8b Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation SEE Question. ASA Monitor 2022; 86:11 doi: https://doi.org/10.1097/01.ASM.0000874208.64950.8b Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: atrial fibrillation, blood transfusion, deep vein thrombosis, hemorrhage, ischemic stroke, kidney diseases, knee replacement arthroplasty, renal failure, acute, seizures, venous thromboembolism You are completing a preoperative evaluation of a 66-year-old woman with a history of deep vein thrombosis who is scheduled for total knee arthroplasty. Based on a recent study, which of the following is the MOST likely outcome for this patient if you administer tranexamic acid (TXA) during the procedure, compared with a similar patient who does not receive TXA? The antifibrinolytic agent TXA is widely used in total hip and knee arthroplasties because of its proven benefit in reducing blood loss. However, there is some concern that TXA may increase the risk of thromboembolic complications, renal dysfunction, or seizure, especially in patients with known risk factors for these complications. A recent retrospective cohort study sought to evaluate the association between the use of TXA and the risk of blood transfusions and complications when used in high-risk patients. Complications were evaluated as the composite of new-onset venous thromboembolism (VTE), myocardial... You do not currently have access to this content.

Evaluation of the safety of tranexamic acid use in pediatric patients undergoing spinal fusion surgery: a retrospective comparative cohort study

BackgroundPediatric spinal fusion may be associated with significant intraoperative blood loss, leading to complications from transfusion, hypoperfusion and coagulopathy. One emerging strategy to mediate these risks is by utilization of the anti-fibrinolytic agent tranexamic acid (TXA). However, concerns regarding potential adverse reactions, specifically postoperative seizures and thrombotic events, still exist. To assess these risks, we examined the perioperative morbidity of TXA use in a large national database.MethodsRetrospective data from pediatric patients (age 18 years or younger), discharged between January 2013 to December 2015, who underwent primary or revision posterior spinal fusions, was collected from the Premier Perspective database (Premier, Charlotte, NC). Patients were stratified by TXA use and records were assessed for complications of new onset seizures, strokes, pulmonary embolisms (PE) or deep vein thromboses (DVT) occurring during the perioperative period.ResultsIn this cohort of 2,633 pediatric patients undergoing posterior spinal fusions, most often to treat adolescent idiopathic scoliosis, 15% received TXA. Overall, adverse events were rare in this patient population. The incidence of seizure, stoke, PE, or DVT in the control group was 0.54% (95% CI, 0.31% to 0.94%) and not significantly different from the TXA group. There was no significant difference in the incidence of DVTs, and no incidences of stroke in either group. There were no new-onset seizures or PEs in patients who received TXA.ConclusionsThe use of TXA was not associated with an increased risk of adverse events including seizure, stroke, PE, and DVT. Our findings support the safety of TXA use in pediatric patients undergoing spinal fusion surgery.

Efficacy and Safety of Tranexamic Acid in Cancer Surgery. An Update of Clinical Findings and Ongoing Research.

In cancer patients undergoing surgery, tumor biology and anticancer treatments can increase the risk of perioperative bleeding and blood transfusions. Notably, blood transfusions can be potentially associated with an increased risk of life-threatening immune responses, acute lung injury, postoperative infections, and thromboembolism. Moreover, the link between perioperative transfusion and increased risk of cancer recurrence cannot be excluded. On the other hand, cancer patients have an increased risk of thromboembolism due to cancer itself and antineoplastic systemic treatments including chemotherapy and anti-angiogenic drugs. In this complex scenario, effective and safe strategies aimed at the prevention of blood transfusions are warranted. This narrative review addresses the efficacy, and the safety of the synthetic antifibrinolytic agent tranexamic acid (TXA) when used perioperatively in cancer surgery. Although in not oncologic surgery the use of TXA has been extensively studied, in the setting of cancer patients requiring surgery, the evidence is scarce. An overview of the ongoing clinical research is also provided.

Synthesis and Hemostatic Activity of New Amide Derivatives.

Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine—natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO− (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1–8 were similar. The obtained results in the presence of amides 1–4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.

Tranexamic acid integrated into platelet-rich fibrin produces a robust and resilient antihemorrhagic biological agent: a human cohort study

To investigate the incorporation of the antifibrinolytic agent tranexamic acid (TA) during platelet-rich fibrin (PRF) formation to produce a robust fibrin agent with procoagulation properties. Blood from healthy volunteers was collected. Into 3 tubes, TA was immediately added in 1-mL, 0.4-mL, and 0.2-mL volumes, and the fourth tube was without additions. After PRF preparation, the clots were weighed in their raw (clot) and membrane forms. PRF physical properties were analyzed using a universal testing system (Instron). Protein and TA levels in the PRF were analyzed using a bicinchoninic acid assay and a ferric chloride assay, respectively. The addition of TA to PRF led to a robust weight compared with sham control. PRF weight was greater in females in all tested groups. The addition of TA also led to greater resilience to tears, especially at 1-mL TA addition to the blood. Furthermore, TA addition led to a greater value of total protein within the PRF and entrapment of TA in the PRF. Addition of TA to a PRF preparation leads to robust PRF with greater protein levels and the amalgamation of TA into the PRF. Such an agent may enhance the beneficial properties of PRF and attribute procoagulation properties to it.

Safety of intravenous tranexamic acid in patients undergoing supratentorial meningiomas resection: protocol for a randomised, parallel-group, placebo control, non-inferiority trial

IntroductionGrowing evidence recommends antifibrinolytic agent tranexamic acid (TXA) to reduce blood loss and transfusions rate in various surgical settings. However, postoperative seizure, as one of the major adverse effects of...

Application of tranexamic acid within the field of dentistry

The antifibrinolytic agent tranexamic acid (TXA) is well known for its capacity to effectively reduce intraoperative blood loss. The effect mechanism of TXA is based on the indirect inhibition of fibrin degradation, whereby existing blood clots within the surgical area are stabilized. Consecutively, the amount of blood loss can be reduced. Due to its great efficacy to minimize blood loss and its low rate of unintended side effects, TXA is regularly used in different surgical fields. Within the field of dentistry TXA is not applied on a regular basis, however, it presents a highly effective and convenient treatment option to reduce bleeding complications.

Effect of Local Tranexamic Acid on the Quality of Bone Healing in a Rat Spinal Fusion Model.

Introduction The use of the antifibrinolytic agent tranexamic acid has positive effects on bleeding control, but our knowledge is still limited regarding how fibrinolysis suppression changes the process of bone formation and the quality of bone. Because of the several side effects of systemic tranexamic acid, topical usage has been established in several procedures. This study aimed to investigate the effect of local tranexamic acid on vertebral fusion by using macroscopic, radiologic, and microscopic techniques. We also attempted to determine the safe dose range in case some doses had negative effects on fusion. Methods Twenty-eight Wistar albino rats underwent intertransverse fusion. All rats were randomized into four groups: groups treated with local tranexamic acid doses of 1 mg/kg (D1), 10 mg/kg (D10), and 100 mg/kg (D100) and the control group with no drug (D0). At the end of the eighth week, all rats were sacrificed for evaluation in terms of palpation, mammography, and histopathologic analysis. Results The manual palpation results presented with lower fusion rates in D10 and D100 groups than in the control group. Radiological examination results were significantly higher in the control group. The histopathologic examination revealed no significant differences between groups in the percent of new bone formation. Conclusions Our results showed that local administration of tranexamic acid reduced the quality and stability of fusion without a delay in bone formation. However, doses of 1 mg/kg did not reduce the stability in the palpation test. Our findings suggest that 1 mg/kg dose is a critical threshold above which tranexamic acid reduced the bone healing process of fusion and that surgeons should consider the doses of local tranexamic acid during surgery.

Associations of preoperative stroke and tranexamic acid administration with convulsive seizures in valvular open-heart surgery

In cardiac surgery, use of the antifibrinolytic agent tranexamic acid (TXA) and acute perioperative stroke are both associated with convulsive seizures. We hypothesized that an older (preoperative) stroke increases the risk of TXA-associated seizures as well. To test this hypothesis, we retrospectively analyzed data from 16,110 patients who had undergone open-heart valvular surgery at our institution between 2009 and 2020. The dosing of TXA was moderate. Use of TXA and a history of stroke were both independently associated with convulsive seizure with an adjusted odds ratio (OR) of 2.40 (95%CI: 1.71–3.37) and 1.79 (95%CI: 1.27–2.54), respectively. Compared to patients without TXA administration, the adjusted OR of experiencing a seizure in TXA patients without a history of stroke was 2.44 (95%CI: 1.71–3.46) and in patients receiving TXA with a history of stroke 4.30 (95%CI: 2.65–6.99). However, there was no significant interaction between TXA use and preoperative stroke on convulsive seizures (P = 0.77). Compared to patients without seizure, for patients with seizure, the inverse probability-weighted ORs of in-hospital mortality and 30-day mortality were 3.58 (95%CI: 2.20–5.83) and 4.04 (95%CI: 2.34–6.98), respectively. We conclude that, in patients undergoing open-heart surgery, a history of stroke is independently associated with convulsive seizures but is not a contraindication for TXA use.

Safety and efficacy of tranexamic acid in minimizing perioperative bleeding in extrahepatic abdominal surgery: meta-analysis.

BackgroundPerioperative bleeding is associated with increased morbidity and mortality in patients undergoing elective abdominal surgery. The antifibrinolytic agent tranexamic acid (TXA) has been shown to reduce perioperative bleeding and mortality risk in patients with traumatic injuries, but there is a lack of evidence for its use in elective abdominal and pelvic surgery. This meta-analysis of RCTs evaluated the effectiveness and safety of TXA in elective extrahepatic abdominopelvic surgery.MethodsPubMed, Embase, and ClinicalTrial.gov databases were searched to identify relevant RCTs from January 1947 to May 2020. The primary outcome, intraoperative blood loss, and secondary outcomes, need for perioperative blood transfusion, units of blood transfused, thromboembolic events, and mortality, were extracted from included studies. Quantitative pooling of data was based on a random-effects model.ResultsSome 19 studies reporting on 2205 patients who underwent abdominal, pelvic, gynaecological or urological surgery were included. TXA reduced intraoperative blood loss (mean difference –188.35 (95 per cent c.i. –254.98 to –121.72) ml) and the need for perioperative blood transfusion (odds ratio (OR) 0.43, 95 per cent c.i. 0.28 to 0.65). TXA had no impact on the incidence of thromboembolic events (OR 0.49, 0.18 to 1.35). No adverse drug reactions or in-hospital deaths were reported.ConclusionTXA reduces intraoperative blood loss during elective extrahepatic abdominal and pelvic surgery without an increase in complications.

Review of Pharmacological Strategies with Repurposed Drugs for Hereditary Hemorrhagic Telangiectasia Related Bleeding.

The diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria: epistaxis, telangiectases, arteriovenous malformations in internal organs, and family history. Genetically speaking, more than 90% of HHT patients show mutations in ENG or ACVRL1/ALK1 genes, both belonging to the TGF-β/BMP9 signaling pathway. Despite clear knowledge of the symptoms and genes of the disease, we still lack a definite cure for HHT, having just palliative measures and pharmacological trials. Among the former, two strategies are: intervention at “ground zero” to minimize by iron and blood transfusions in order to counteract anemia. Among the later, along the last 15 years, three different strategies have been tested: (1) To favor coagulation with antifibrinolytic agents (tranexamic acid); (2) to increase transcription of ENG and ALK1 with specific estrogen-receptor modulators (bazedoxifene or raloxifene), antioxidants (N-acetylcysteine, resveratrol), or immunosuppressants (tacrolimus); and (3) to impair the abnormal angiogenic process with antibodies (bevacizumab) or blocking drugs like etamsylate, and propranolol. This manuscript reviews the main strategies and sums up the clinical trials developed with drugs alleviating HHT.

Tranexamic Acid for Acute Hemorrhage: A Narrative Review of Landmark Studies and a Critical Reappraisal of Its Use Over the Last Decade.

The publication of the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) study and its intense dissemination prompted a renaissance for the use of the antifibrinolytic agent tranexamic acid (TXA) in acute trauma hemorrhage. Subsequent studies led to its widespread use as a therapeutic as well as prophylactic agent across different clinical scenarios involving bleeding, such as trauma, postpartum, and orthopedic surgery. However, results from the existing studies are confounded by methodological and statistical ambiguities and are open to varied interpretations. Substantial knowledge gaps remain on dosing, pharmacokinetics, mechanism of action, and clinical applications for TXA. The risk for potential thromboembolic complications with the use of TXA must be balanced against its clinical benefits. The present article aims to provide a critical reappraisal of TXA use over the last decade and a "thought exercise" in the potential downsides of TXA. A more selective and individualized use of TXA, guided by extended and functional coagulation assays, is advocated in the context of the evolving concept of precision medicine.

Mitigation of Vascular Permeability Using Bradykinin Receptor Antagonist and Anti-Fibrinolytic Agent in Rats with Polytrauma and Hemorrhagic Shock

Introduction: Clinical studies suggest that one third of patients suffering major trauma develop acute traumatic coagulopathy (ATC), which is associated with increased morbidity and mortality. Recent evidence in both animal and clinical studies has shown that development of ATC is associated with an increase in fibrinolytic activity, initiated by an elevation in tissue plasminogen activator (tPA) immediately after trauma. Previous studies demonstrate that administration of the anti-fibrinolytic agent tranexamic acid (TXA) not only inhibits fibrinolytic activity in traumatized tissue but also attenuates lung edema after resuscitation in rats with polytrauma and hemorrhagic shock, suggesting a potential correlation between fibrinolysis and vascular permeability. One of the underlying mechanisms of acute elevation in vascular permeability after severe trauma is associated with an elevation of bradykinin activity due to activation of the tPA-plasmin-bradykinin pathway. This study will test the hypothesis that early intervention by administration of a bradykinin receptor antagonist with or without TXA prior to resuscitation attenuates edema in the tissues after resuscitation in rats with polytrauma/hemorrhagic shock. Method: Sprague-Dawley rats (350-450g) under anesthesia with isoflurane received polytrauma followed by hemorrhage (40% of blood volume). The rats either received vehicle (normal saline) or bradykinin receptor-2 antagonist (BR-2A (HOE140, 0.5mg/kg)), TXA (20mg/kg) or BR-2A/TXA via femoral vein at 45min after trauma (n=6-8/each group), followed by resuscitation with Lactated Ringer's solution (20% of blood volume) at 60min after trauma. Four normal rats, not undergoing surgical procedures were treated as normal control. At 2hr after trauma (1hr after resuscitation), the rats were euthanized and the tissues from internal organs were harvested and weighed for wet weight. The tissue samples were then transferred to a 600C oven for 10-14 days. The dry weight was determined when the weight of dried tissue was constant for three consecutive days. The wet-dry weight ratio was then calculated to represent the water content for each tissue. The wet-dry weight ratio was also measured in traumatized tissues collected from the injured sites of liver, intestine and skeletal muscle (at hindlimb). At 2hr after trauma, prothrombin time (PT) was measured for systemic hemostatic condition, and the resuscitation outcome was assessed by lactate levels. Results: The wet/dry weight ratio is different in organs due to underlying structure and water content. Trauma, hemorrhage and resuscitation led to a significant elevation of wet/dry weight ratio in a majority of the organs (except for heart, kidney, and stomach). The wet/dry weight ratio was significantly higher in traumatized tissues than non-traumatized tissues (at liver, intestine and skeletal muscle). BR-2A significantly decreased the wet/dry weight ratio of the brain (4.51±0.03 (BR-2A) vs 4.64±0.03 (Vehicle)), but had no effect on the other organs. TXA significantly reduces the wet/dry weight ratio of the lung and intestine (lung: 5.02±0.07 (BR-2A) vs 5.23±0.06 (Vehicle), p=0.003; Intestine: 4.16±0.10 (BR-2A) vs 4.45±0.07 (Vehicle), p=0.036) but not in the brain and other tissues. The combination of BR-2A with TXA significantly decreased elevation of wet/dry weight ratio of the brain, lung and intestine, but there was no synergistic effect on wet/dry weight ratio found in any organs. However, the rats treated with combination treatment of BR-2A and TXA had the lowest lactate level at 2hr after trauma as compared to rats treated with vehicle (1.85±0.15 vs 3.39±0.29 mmol/l, p=0.032) suggesting an overall improvement of resuscitation outcome. BR-2A, TXA or a combination of the two did not cause significant change in MAP and HR, and had no significant effect on systemic coagulopathy (elevation of prothrombin time) at 2hr after trauma and hemorrhage. Conclusions: This study suggests that BR-2A and TXA independently mitigate tissue-specific vascular permeability in trauma and hemorrhagic shock. Future studies are necessary to investigate the optimal dose and timing of administration of BR-2A or BR-2A with TXA in trauma and hemorrhagic shock to improve the outcome and efficacy of treatment. Disclosures No relevant conflicts of interest to declare.

A survey of anaesthetists' use of tranexamic acid in noncardiac surgery.

Major bleeding in noncardiac surgery is common and associated with serious complications. The antifibrinolytic agent tranexamic acid (TXA) reduces bleeding and may reduce the risk of these complications. TXA also may have immunomodulatory effects that could reduce surgical site infection. Clinical trials of TXA in noncardiac surgery have been insufficiently powered to evaluate its efficacy and safety. Therefore, large randomised controlled trials of its use in noncardiac surgery are required. To ensure that future clinical trials are feasible and acceptable, we undertook a survey of Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA). Our aims were to ascertain current patterns of TXA administration and to assess the acceptability of randomising patients to intravenous TXA or placebo. A 12-item survey was electronically mailed to 1001 ANZCA Fellows. Two hundred and eighty nine responses were received and analysed (response rate 29%). Ninety-eight percent of respondents had used intravenous TXA in noncardiac surgery; 67% give TXA routinely for lower limb arthroplasty, with smaller proportions giving TXA for spinal surgery (40%) and other major orthopaedic surgery (28%). Almost half (49%) give TXA routinely for major trauma surgery. Thirty-six percent indicated that they did not give TXA for major vascular, abdominal, pelvic or thoracic surgery. The majority administered TXA as a single, fixed dose. Fifty-seven percent agreed that there is uncertainty about the relative risks and benefits of perioperative TXA in noncardiac surgery and 87% agreed that large definitive trials determining the safety and efficacy of perioperative TXA in noncardiac surgery are required. These results indicate that for ANZCA Fellows the use of TXA in noncardiac surgery is highly variable, that there is uncertainty about the safety and efficacy of TXA, and that a large trial would be acceptable.

Dynamic changes of urinary proteins in a rat model of acute hypercoagulable state induced by tranexamic acid.

The hypercoagulable state leads to the development of thrombotic diseases, but it is difficult to diagnose due to the lack of available biomarkers. This study aimed to investigate systematic changes of the urinary proteome in the acute hypercoagulable state. A rat model of the acute hypercoagulable state was induced by an antifibrinolytic agent tranexamic acid and urine samples were collected for proteomic analysis by liquid chromatography-tandem mass spectrometry. A total of 28 differential proteins were detected in the urinary proteome of the model rats, of which 12 had been previously considered as candidate biomarkers such as myoglobin, and 10 had been considered stable in healthy human urine. Of the 28 differentially expressed proteins 18 had counterparts in humans. Of these 18 proteins, 10 were members of the human core urinary proteome distributed in a variety of human tissues but concentrated in the urinary and digestive systems. Fumarylacetoacetase was verified as a potential marker of the acute hypercoagulable state by Western blot analysis. In conclusion, urine proteome analysis is a powerful approach to identify potential biomarkers of acute hypercoagulable state.