Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis.
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ABSTRACT:
SUBMITTER: Pabinger I
PROVIDER: S-EPMC5429347 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
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Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis.
Pabinger Ingrid I Fries Dietmar D Schöchl Herbert H Streif Werner W Toller Wolfgang W
Wiener klinische Wochenschrift 20170421 9-10
Uncontrolled massive bleeding with subsequent derangement of the coagulation system is a major challenge in the management of both surgical and seriously injured patients. Under physiological conditions activators and inhibitors of coagulation regulate the sensitive balance between clot formation and fibrinolysis. In some cases, excessive and diffuse bleeding is caused by systemic activation of fibrinolysis, i. e. hyperfibrinolysis (HF). Uncontrolled HF is associated with a high mortality. Polyt ...[more]
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Project description:The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)-challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 μg/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, -0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels.
| S-EPMC10025092 | biostudies-literature
Project description:BackgroundGastrointestinal bleeding is a common emergency that causes substantial mortality worldwide. Acute upper and lower gastrointestinal bleeding accounts for about 75,000 hospital admissions each year in the UK and causes the death of about 10% of these patients. Tranexamic acid has been shown to reduce the need for blood transfusion in surgical patients and to reduce mortality in bleeding trauma patients, with no apparent increase in thromboembolic events. A systematic review of clinical trials of upper gastrointestinal bleeding shows a reduction in the risk of death with tranexamic acid but the quality of the trials was poor and the estimates are imprecise. The trials were also too small to assess the effect of tranexamic acid on thromboembolic events.MethodsHALT-IT is a pragmatic, randomised, double-blind, placebo-controlled trial which will determine the effect of tranexamic acid on mortality, morbidity (re-bleeding, non-fatal vascular events), blood transfusion, surgical intervention, and health status in patients with acute gastrointestinal bleeding. Eight thousand adult patients who fulfil the eligibility criteria will be randomised to receive tranexamic acid or placebo. Adults with significant acute upper or lower gastrointestinal bleeding can be included if the responsible doctor is substantially uncertain as to whether or not to use tranexamic acid in that particular patient. Trial treatment consists of a loading dose of tranexamic acid (1 g by intravenous injection) or placebo (sodium chloride 0.9%) given as soon as possible after randomisation, followed by an intravenous infusion of 3 g tranexamic acid or placebo (sodium chloride 0.9%) over 24 hours. The main analyses will compare those allocated tranexamic acid with those allocated placebo, on an intention-to-treat basis. Results will be presented as effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time to treatment, source of bleeding (upper versus lower), suspected variceal bleeding and severity of bleeding. A study with 8,000 patients will have over 90% power to detect a 25% reduction in mortality from 10% to 7.5%.Trial registrationCurrent Controlled Trials ISRCTN11225767 (registration date: 3 July 2012); Clinicaltrials.gov NCT01658124 (registration date: 26 July 2012).
| S-EPMC4253634 | biostudies-literature
Project description:BACKGROUND:The CRASH-2 trial showed that tranexamic acid (TXA) administration reduces mortality in bleeding trauma patients. However, the effect appeared to depend on how soon after injury TXA treatment was started. Treatment within 3 h reduced bleeding deaths whereas treatment after 3 h increased the risk. We examine how patient characteristics vary by time to treatment and explore whether any such variations explain the time-dependent treatment effect. METHODS:Exploratory analysis were carried out, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo-controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examine how patient characteristics (age, type of injury, presence or absence of head injury, Glasgow coma scale (GCS), systolic blood pressure and capillary refill time) vary with time to treatment and use univariable (restriction) and multivariable methods to examine whether any such variations explain the time-dependent effect of TXA. If not explained by differences in patient characteristics, we planned to conduct separate prespecified subgroup analyses for the early benefit and late harm. RESULTS:There was no substantial variation in age or capillary refill by time to treatment. However, the proportion of patients with blunt trauma, the proportion with head injury and mean systolic blood pressure increased as time to treatment increased. Mean GCS decreased as time to treatment increased. Analyses restricted to patients with blunt trauma, those without head injury and those with a systolic blood pressure <100 mmHg showed that these characteristics did not explain the time-dependent treatment effect. In a multivariable analysis the interaction with time to treatment remained highly significant (p?<?0.0001). Separate subgroup analyses that examine how the benefits of early TXA treatment and the harms of late TXA treatment vary by systolic blood pressure (?75, 76-89, >89 mmHg); GCS (severe 3-8, moderate 9-12, mild 13-15); and type of injury (penetrating versus blunt) showed no significant heterogeneity. CONCLUSIONS:The time-dependent effect of TXA in bleeding trauma patients is not explained by the type of injury, the presence or absence of head injury or systolic blood pressure. When given within 3 h of injury, TXA reduces death due to bleeding regardless of type of injury, GCS or blood pressure. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00375258 . Registered on 11 September 2006.
| S-EPMC5282847 | biostudies-literature
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| S-EPMC1727106 | biostudies-other
Project description:Background/purposeTranexamic acid (TA) is one of the commonly used local hemostatic agents for dental procedures and a previous study has demonstrated a significantly lower incidence of post-procedural bleeding (PPB) in patients taking warfarin and received local TA treatment after the dental procedures than those who took warfarin and did not receive local TA treatment. However, it is still unknown whether post-procedural local TA treatment can lower the bleeding risk to the same level as individuals who do not take oral anticoagulant (OAC). The current study aimed to compare the PPB risk in patients who took OAC and received local TA treatment after the dental procedures and individuals who did not take OAC and underwent similar dental procedures.Materials and methodsWe systematically searched primary researches from two databases and four eligible cohort studies were identified. The bleeding incidence was collected from each study and the pooled odds ratio (OR) and 95% confidence interval (CI) of PPB were calculated using Mantel-Haenzel method.ResultsThe analysis revealed a higher risk of PPB in patients who took OAC and received local TA treatment after the dental procedures than individuals who did not take OAC and underwent similar dental procedures with the pooled OR of 2.4, although the pooled effect estimate had a relatively wide 95% CI with non-statistically difference (0.69-8.12).ConclusionThis study results serve as a reminder to dentists that the increased risk of PPB in those who took OAC is not entirely resolved by the local TA treatment.
| S-EPMC6446020 | biostudies-literature
Project description:ObjectiveTo assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients.DesignSystematic review and meta-analysis.Data sourcesCochrane central register of controlled trials, Medline, and Embase, from inception to September 2011, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of relevant articles.Study selectionRandomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in surgical patients. Outcome measures of interest were the number of patients receiving a blood transfusion; the number of patients with a thromboembolic event (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number of deaths. Trials were included irrespective of language or publication status.Results129 trials, totalling 10,488 patients, carried out between 1972 and 2011 were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; P<0.001). This effect remained when the analysis was restricted to trials using adequate allocation concealment (0.68, 0.62 to 0.74; P<0.001). The effect of tranexamic acid on myocardial infarction (0.68, 0.43 to 1.09; P = 0.11), stroke (1.14, 0.65 to 2.00; P = 0.65), deep vein thrombosis (0.86, 0.53 to 1.39; P = 0.54), and pulmonary embolism (0.61, 0.25 to 1.47; P=0.27) was uncertain. Fewer deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; P = 0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (0.67, 0.33 to 1.34; P = 0.25). Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years.ConclusionsStrong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.
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Project description:ImportanceEvidence has emerged on the efficacy of tranexamic acid to control blood loss and postoperative complications after rhinoplasty.ObjectiveTo investigate the results of tranexamic acid use to reduce intraoperative bleeding, postoperative eyelid edema, and periorbital ecchymosis in rhinoplasty.Data sources and study selectionFor this systematic review of randomized clinical trials, searches were performed in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, Science Direct, Google Scholar, OpenThesis, and ClinicalTrials.gov from inception to December 23, 2017. Key words included tranexamic acid, rhinoplasty, and nasal surgical procedures. The following elements were used to define eligibility criteria: (1) population: patients undergoing rhinoplasty surgery; (2) intervention and controls: tranexamic acid vs placebo solution or no-treatment control group; (3) outcomes: intraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis, and thromboembolic events; and (4) study type: randomized clinical trials.Data extraction and synthesisTwo reviewers extracted data and assessed study quality according to the Cochrane guidelines for randomized clinical trials. Treatment effects were defined as weighted mean difference (WMD) and 95% CIs. The strength of evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation rating system.Main outcomes and measuresIntraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis. To calculate the effect sizes, means and SDs were obtained for each study group and outcome of interest.ResultsFive studies comprising 276 patients were included in the systematic review: 177 patients (64.1%) were women, and mean age was 26.8 (range, 16-42) years. Four studies comprising 246 patients estimated the amount in intraoperative bleeding as a primary outcome and were included in the meta-analysis. Eyelid edema and ecchymosis were evaluated as outcomes in 2 studies. Tranexamic acid was associated with reduced bleeding during rhinoplasty was found (WMD, -42.28 mL; 95% CI, -70.36 to -14.21 mL), with differences (P?=?.01) between oral (WMD, -61.70 mL; 95%?CI, -83.02 to -40.39 mL; I2?=?0%) and intravenous (WMD, -23.88 mL; 95% CI, -45.19 to -2.58 mL; I2?=?56%) administration. Eyelid edema and ecchymosis scores in patients receiving tranexamic acid were significantly lower compared with the control group within the first postoperative week: lower eyelid edema, WMD, -0.76; 95% CI, -1.04 to -0.49 and lower eyelid ecchymosis, WMD, -0.94; 95% CI, -1.80 to -0.08. No cases of thromboembolic events were reported.Conclusions and relevanceCurrent available evidence suggests that preoperative administration of tranexamic acid is safe and may reduce intraoperative bleeding as well as postoperative eyelid edema and ecchymosis in patients undergoing rhinoplasty.
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Project description:Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients.
| S-EPMC4738442 | biostudies-other
Project description:Tranexamic acid (TXA) is an antifibrinolytic pharmacological agent, but its use in gastrointestinal bleeding remains contentious. Moreover, studies on the timing of TXA administration are limited. We examined whether early TXA administration reduced the risk of mortality in patients with gastrointestinal bleeding in a Taiwanese population. We used the National Health Insurance Research Database to identify patients diagnosed with gastrointestinal bleeding with early and late TXA treatment. We defined early treatment as initial TXA treatment in an emergency department and late treatment as initial TXA treatment after hospitalization. Mortality within 52 weeks was the primary outcome. A multivariable analysis using a multiple Cox regression model was applied for data analysis. Propensity score matching (PSM) was performed to reduce the potential for bias caused by measured confounding variables. Of the 52,949 selected patients with gastrointestinal bleeding, 5127 were assigned to either an early or late TXA treatment group after PSM. The incidence of mortality was significantly decreased during the first and fourth weeks (adjusted HR (aHR): 0.65, 95% CI: 0.56−0.75). A Kaplan−Meier curve revealed a significant decrease in cumulative incidence of mortality in the early TXA treatment group (log-rank test: p < 0.0001). Multiple Cox regression analysis revealed significantly lower mortality in the early TXA treatment group compared with the late treatment group (aHR: 0.64, 95% CI: 0.57−0.73). Thromboembolic events were not significantly associated with early or late TXA treatment (aHR: 1.03, 95% CI: 0.94−1.12). A Kaplan−Meier curve also revealed no significant difference in either venous or arterial events (log-rank test: p = 0.3654 and 0.0975, respectively). In conclusion, early TXA treatment was associated with a reduced risk of mortality in patients with gastrointestinal bleeding compared with late treatment, without an increase in thromboembolic events. The risk of rebleeding and need for urgent endoscopic intervention require further randomized clinical trials.
| S-EPMC8951209 | biostudies-literature
Project description:BACKGROUND:Topical administration of tranexamic acid (TXA) may be an alternative to intravenous administration to reduce bleeding with a lower risk of systemic adverse events. The aim of this study was to investigate whether moistening a surgical wound with TXA before closure, leaving a thin film of drug only, would reduce postoperative bleeding. METHODS:This was a two-centre, stratified, parallel-group, placebo-controlled, double-blind RCT. Patients undergoing mastectomy with or without axillary lymph node clearance were randomized 1?:?1 to moistening of wound surface before closure with either 25?mg/ml TXA or 0·9 per cent sodium chloride (placebo). The primary endpoint was postoperative bleeding as measured by drain production in the first 24?h. Secondary endpoints were early haematoma, total drain production, postoperative complications and late aspirations of seroma within 3?months. RESULTS:Between 1 January 2016 and 31 August 2018, 208 patients were randomized. Two patients were converted to a different surgical procedure at surgery, and four did not receive the intervention owing to technical error. Thus, 202 patients were included in the study (101 in the TXA and 101 in the placebo group). TXA reduced mean drain production at 24?h (110 versus 144?ml; mean difference 34 (95 per cent c.i. 8 to 60) ml, P = 0·011). One patient in the TXA group had early haematoma compared with seven in the placebo group (odds ratio (OR) 0·13 (95 per cent c.i. 0·02 to 1·07); P = 0·057). There was no significant difference in postoperative complications between TXA and placebo (13 versus 10; OR 1·11 (0·45 to 2·73), P = 0·824) or need for late seroma aspirations (79 versus 67 per cent; OR 1·83 (0·91 to 3·68), P = 0·089). CONCLUSION:Moistening the wound with TXA 25?mg/ml before closure reduces postoperative bleeding within the first 24?h in patients undergoing mastectomy. Registration number: NCT02627560 (https://clinicaltrials.gov).
| S-EPMC7093788 | biostudies-literature