Safety Of Tranexamic Acid Use Research Articles

EVALUATING THE BLOOD-SPARING EFFICACY AND SAFETY OF TRANEXAMIC ACID IN TOTAL KNEE ARTHROPLASTY

Objectives: Tranexamic acid (TXA) is an antifibrinolytic agent that effectively reduces bleeding both during and after surgery. The purpose of our study was to assess the effectiveness and safety of TXA use in reducing blood loss in uncomplicated primary total knee arthroplasty (TKA) without complications. Methods: This is a prospective, open-label, comparative study that includes patients who are undergoing unilateral primary TKA. The patients were divided into two groups: Group I, which is a control group, did not receive any doses of TXA, and Group II received three doses of intravenous TXA: 15 mg/kg TXA was administered 30 min before incision, followed by post-operative doses of 10 mg/kg TXA at 3 and 6 h. The primary objectives of the study were to measure the total blood loss (TBL) and Hemoglobin (Hb) drop, which were calculated preoperatively and on the third post-operative day. The secondary objectives were to determine transfusion rates, incidences of symptomatic deep vein thrombosis, and thromboembolic events (TE). Results: In this study, a total of 57 patients underwent unilateral TKA. The TBL in Group I was 861.67±167.65 mL, compared to 780.05±158.05 mL in Group II (p<0.001). The study also found that the Hb drop was significantly lower (2.78±0.36 vs. 2.3±0.37) with IV TXA. Furthermore, neither group required transfusions, nor were any thromboembolic complications noted for up to 6 months post-operation. Conclusion: Our study supports the use of TXA in TKA, as it effectively reduces perioperative blood loss, decreases the need for blood transfusions, and does not increase the risk of TE.

A Systematic Review of the Efficacy and Safety of Tranexamic Acid in Facelift Surgery.

Tranexamic acid (TXA) has become widely utilized in different specialities including facelift surgery. The aim of this review was to robustly evaluate the quality of available evidence on the efficacy and safety of TXA use in facelift surgery. We searched the MEDLINE (National Institutes of Health, Bethesda, MD), Embase (Elsevier, Amsterdam, the Netherlands), CINAHL (EBSCO Information Services, Ipswich, MA), Cochrane Central Register of Controlled Trials (CENTRAL; Wiley, Hoboken, NJ), Google Scholar (Alphabet Inc. Mountain View, CA), Science Citation Index (Clarivate, London, UK), and Latin American and Caribbean Center on Health Sciences Information (LILACS; São Paulo, Brazil) databases for randomized controlled trials (RCTs) and observational studies. Primary outcomes were blood loss, postoperative hematoma, ecchymosis, and swelling, in addition to technical considerations and complications. We assessed review quality with the AMSTAR 2 tool, study quality with Grading of Recommendations, Assessment, Development, and Evaluations approach (GRADE) tool, and the risk of bias with Cochrane's RoB 2.0 tool for RCTs and ROBINS-I for nonrandomized studies. Of the 368 articles, a total of 3 studies including 150 patients met the inclusion criteria. The RCT reported a significant reduction in postoperative serosanguineous collections in the TXA group (P < .01), and in surgeon-rated postoperative ecchymosis and bruising. The prospective cohort study reported reduced drainage output in first 24 hours in the TXA group (P < .01). The retrospective cohort study reported lower intraoperative blood loss, mean postoperative day 1 drain output, percentage of drain removal on postoperative day 1, and number of days to drain removal in the TXA group (all P < .01). The quality of studies was moderate, and this review was the highest rated compared to previous reviews, as per the AMSTAR 2 tool. Based on limited literature, TXA improves clinical outcomes regardless of the route of administration. Topical TXA is an emerging route, expediting drain removal and reducing blood loss. Future Level I high-quality studies are required.

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.

Effectiveness and Safety of Tranexamic Acid Use in Acute Traumatic Injury in the Prehospital and In-hospital Settings: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess efficacy and safety of tranexamic acid (TXA) use in acute traumatic injuries. PubMed and Cochrane libraries were searched for relevant RCTs published between January 2011 and January 3, 2021. Cohen's Q Test for heterogeneous effects was used to determine the appropriateness of fixed versus random effects models. Twenty-two studies met inclusion criteria. Meta-analysis of relative risk of mortality between treatment and placebo groups in the in-hospital, and perioperative settings was not significant. However, the risk of mortality is significantly lower in the treatment versus placebo group when TXA was given as loading dose only. Ten of the 11 studies evaluating perioperative use of TXA included in systematic review found significantly lower blood loss in the treatment compared with placebo groups, but results of meta-analysis showed no significant difference. Results of meta-analysis indicate that the risk of venous thromboembolism (VTE) in the in-hospital treatment group is greater than that of the placebo. In subset analysis of studies using only a single loading dose, there were no significant differences in VTE. Systematic review supports TXA benefits are most evident when given shortly after injury and meta-analysis supports TXA reduces mortality as a single loading dose. Systematic review supports perioperative use of TXA when large volume blood loss is anticipated. Meta-results showed no significant difference in risk of thromboembolism in single-dose TXA treatment compared with placebo. These findings suggest that TXA is safe and effective for control of traumatic bleeding.

The efficiency and safety of intravenous tranexamic acid administration in open reduction and internal fixation of pelvic and acetabular fractures.

This study aimed to investigate the efficiency and safety of tranexamic acid use in open reduction and internal fixation of pelvis and acetabulum fractures. 73 consecutive patients were included. 1000mg TXA was administered intravenously to all patients before surgery. The patients were evaluated on the basis of preoperative, postoperative first and third day hemoglobin-hematocrit values, amount of drainage collected, total blood loss, transfusion rates and complications. Mean operative time was 120.1min. Average decrease in hematocrit levels between preoperative and postoperative first day was 2.1g/dL. Average collected blood from the drain was 177mL. Mean total blood loss was 1137mL. Transfusion rate of the patients was 21%. Mean transfused units was 0.9 units. Three patients died within 3 weeks after the operation due to myocardial infarction, acute kidney failure and pneumonia. There were no cases of symptomatic venous or pulmonary thromboembolism during the 90days of follow-up. Use of TXA in pelvic and acetabular fractures was found to be effective in reducing total blood loss, hemoglobin drop and transfusion rates without increasing venous and pulmonary thromboembolism in our series.

Effects of Tranexamic Acid on Hemoptysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Hemoptysis, a common symptom of different lung diseases, engenders shortness of breath and increased mortality. Tranexamic acid (TXA), a commonly used antifibrinolytic agent, can control bleeding. However, the effects of its use on pulmonary hemorrhage have rarely been discussed. We conducted this systematic review and meta-analysis of randomized controlled trials (RCTs) of TXA for hemoptysis to investigate its effectiveness in reducing hemoptysis volume and duration. We searched the Cochrane Library, Embase, PubMed (including MEDLINE), and Scopus databases for relevant RCTs. Two of the authors individually assessed study quality by using the Cochrane risk-of-bias (RoB) 2.0 tool, and the pooled results were evaluated using RevMan 5.3. We obtained 617 articles, of which four RCTs met eligibility criteria. The pooled results demonstrated no significant differences in bleeding duration or hemoptysis resolution between the TXA and control groups. Nevertheless, TXA use reduced bleeding volume (mean difference [MD] = - 56.21mL; 95% CI - 94.70 to - 17.72mL), further intervention risk (Peto odds ratio = 0.24; 95% CI 0.08-0.67; I2 = 0%), and length of hospital stay (MD = - 1.62days; 95% CI - 2.93 to - 0.31; I2 = 0%). TXA use was observed to reduce bleeding volume, further intervention risk, and length of hospital stay in patients with hemoptysis; however, our results may have low statistical power because of limited sample size. Additional large-scale RCTs are thus warranted to confirm the effectiveness and safety of TXA use.

Utilization, effectiveness, and safety of tranexamic acid use in hip fracture surgery: A population-based study

ObjectiveTo assess the effect of tranexamic acid (TXA) use in hip fracture surgery. MethodsA retrospective cohort study was performed using the Premier Healthcare database. A propensity score matching approach was applied to assess associations between TXA use and blood transfusion, perioperative complications, length of stay (LOS), and hospitalization cost. ResultsIn 153,169 patients, TXA use was associated with a 17% decrease in odds of blood transfusion, no increase in the risk of perioperative complications, 16% shorter LOS, and minimal effects on hospitalization cost. ConclusionOur results are in support of a wider use of TXA in hip fracture surgery. Level of evidenceLevel III.

The Use of Tranexamic Acid (TXA) for the Management of Hemorrhage in Trauma Patients in the Prehospital Environment: Literature Review and Descriptive Analysis of Principal Themes.

Tranexamic acid (TXA) is an antifibrinolytic agent used to prevent traumatic exsanguination. It was first introduced to clinical practice for the management of patients with bleeding disorders, especially adapted to reduce bleeding in hemophiliacs undergoing oral surgical interventions. TXA exerts its action on the coagulation process by competitively inhibiting plasminogen activation, thereby reducing conversion of plasminogen into plasmin. This ultimately prevents fibrinolysis and reduces hemorrhage. Thus, TXA may be well suited for the management of traumatic hemorrhage in the prehospital setting.Despite multiplicity of studies on the use of TXA in clinical practice, there is no consensus regarding the use of TXA for the management of hemorrhage in trauma patients in the prehospital environment. Thus, a review on this topic was warranted. An extensive literature search yielded 14 full journal articles which met the inclusion criteria. These articles were thoroughly analyzed and the following themes were identified: "dose of TXA administration," "route of TXA administration," "optimal window of TXA administration," "safety of TXA use," "clinical effectiveness of TXA application," and the "feasibility of TXA use in the prehospital setting."Overall, to achieve the best possible outcomes, the literature supports the use of a loading dose of 1 g of TXA, followed by 1 g infusion over 8 h, given by intravenous administration within a 3-h window period of traumatic injury. TXA is very effective and safe to use in the prehospital setting, and its use is clinically and economically feasible.

Short-term safety of tranexamic acid use in posterior cervical decompression and fusion surgery

Posterior cervical decompression and fusion (PCDF) can result in substantial blood loss, leading to blood transfusions and associated complications, such as infections, hypotension and organ damage. The antifibrinolytic tranexamic acid (TXA), an inhibitor of the activation of plasminogen, has been shown to be beneficial in multiple surgical procedures without any apparent increase in postoperative complications. However, there are only few studies reporting TXA utilization in cervical spine surgery and there is currently no literature detailing the short-term safety of its use in this setting. The purpose of our study is to determine the safety profile of TXA in posterior cervical decompression and fusion. From January 2015 to April 2018, 47 patients were identified to have undergone PCDF, 19 with the utilization of a TXA protocol at our institution. The incidence of adverse events was evaluated in the perioperative period and at 1 month follow-up. Of 39 patients, Nineteen (49%) received TXA as per our instructional protocol and 20 (51%) did not. Post-operative blood was significantly reduced (453 ml vs 701 ml; p = 0.03) in the group that received TXA. There was also a significant reduction in duration of surgery associated with TXA use (269 min vs 328 min; p = 0.05). There were no complications on the first 30 days after surgical intervention on the TXA group. TXA use during PCDF is a safe, effective method to reduce postoperative blood loss. Considering the limited number of patients in this study, these results should be validated on a larger group of patients.

Intramuscular Tranexamic Acid in Tactical and Combat Settings.

Uncontrolled hemorrhage remains a leading cause of preventable death in tactical and combat settings. Alternate routes of delivery of tranexamic acid (TXA), an adjunct in the management of hemorrhagic shock, are being studied. A working group for the Committee for Tactical Emergency Casualty Care reviewed the available evidence on the potential role for intramuscular (IM) administration of TXA in nonhospital settings as soon as possible from the point of injury. EMBASE and MEDLINE/PubMed databases were sequentially searched by medical librarians for evidence of TXA use in the following contexts and/or using the following keywords: prehospital, trauma, hemorrhagic shock, optimal timing, optimal dose, safe volume, incidence of venous thromboembolism (VTE), IM bioavailability. A total of 183 studies were reviewed. The strength of the available data was variable, generally weak in quality, and included laboratory research, case reports, retrospective observational reviews, and few prospective studies. Current volume and concentrations of available formulations of TXA make it, in theory, amenable to IM injection. Current bestpractice guidelines for large-volume injection (i.e., 5mL) support IM administration in four locations in the adult human body. One case series suggests complete bioavailability of IM TXA in healthy patients. Data are lacking on the efficacy and safety of IM TXA in hemorrhagic shock. There is currently insufficient evidence to support a strong recommendation for or against IM administration of TXA in the combat setting; however, there is an abundance of literature demonstrating efficacy and safety of TXA use in a broad range of patient populations. Balancing the available data and risk- benefit ratio, IM TXA should be considered a viable treatment option for tactical and combat applications. Additional studies should focus on the optimal dose and bioavailability of IM dosing of patients in hemorrhagic shock, with assessment of potential downstream sequelae.

Can tranexamic acid conserve blood and save operative time in spinal surgeries? A meta-analysis

Background ContextIt is widely accepted that tranexamic acid (TXA) effectively reduces blood losses and transfusions in major surgeries. However, limited studies investigated the role of TXA in conserving blood and saving operative time in spine surgeries. PurposeThis meta-analysis was conducted to gather scientific evidence for TXA efficacy on conserving blood and saving operative time in spine surgeries. Study DesignA meta-analysis was performed. Patient SampleEighteen RCTs and 18 non-RCT studies involving 2,572 patients were included in the final analyses, comparing the effectiveness of intravenous TXA with a placebo/no treatment group. Outcome MeasuresOutcomes of interest included intraoperative, postoperative, and perioperative blood losses, allogeneic blood transfusion rates, cell salvage transfusion amounts, operative time, and the number of postoperative thrombosis events. MethodsAn exhaustive literature search was conducted in the MEDLINE and EMBASE databases from January 2000 through March 2017. Meta-analysis was performed using Review Manager (RevMan) version 5.0. For continuous outcomes, the means and standard deviations were pooled to a mean difference and 95% confidence interval (CI). Odds ratios (OR) and 95% CI were calculated for dichotomous outcomes. The quantity of heterogeneity was assessed using I2 statistics. When there was no statistical evidence of substantial heterogeneity (I2≤50%), a fixed-effect model was adopted; otherwise, a random-effect model was chosen. Subgroup analysis was performed when more than three studies were included on one issue, based on low or high the dose of TXA. Beijing Talent Fund (2016) was received to support this work. ResultsSignificantly reduced intraoperative (weighted mean difference [WMD]=−280.09.00, p<.00001), postoperative (WMD=−120.15, p<.00001), perioperative (WMD=−310.86, p<.00001) blood losses, cell salvage transfusion amount (WMD=−471.79, p=.01), perioperative transfusion rate (odds ratio [OR], 0.33 [0.17, 0.65], p=.001), and operative time (WMD=−4.69, p=.003) were observed in TXA group. Furthermore, subgroup analysis revealed that high-dose TXA could reduce both intraoperative-perioperative allogeneic transfusion rates and operative time, whereas low dose of the drug does not convey such effects. ConclusionsWith the most comprehensive literature inclusion up to the present, this meta-analysis suggests that intravenous TXA use constitutes an important measure for conserving blood and saving operative time in spinal surgeries. High-dose TXA significantly reduces intraoperative-perioperative allogeneic transfusion rates and operative time, whereas low-dose TXA does not convey such efficacies. Larger prospective trials are still required to define the optimal regimen and to confirm the safety of TXA use in such surgeries.

Military use of tranexamic acid in combat trauma: Does it matter?

Tranexamic acid (TXA) has been previously reported to have a mortality benefit in civilian and combat-related trauma, and was thus added to the Joint Theater Trauma System Damage Control Resuscitation Clinical Practice Guideline. As part of ongoing system-wide performance improvement, the use of TXA has been closely monitored. The goal was to evaluate the efficacy and safety of TXA use in military casualties and provide additional guidance for continued use. A total of 3,773 casualties were included in this retrospective, observational study of data gathered from a trauma registry. The total sample, along with three subsamples for massive transfusion patients (n = 784), propensity-matched sample (n = 1,030), and US/North Atlantic Treaty Organization (NATO) military (n = 1,262), was assessed for administration of TXA and time from injury to administration of TXA. Outcomes included mortality and occurrence of pulmonary embolism and deep vein thrombosis. Multivariable proportional hazards regression models with robust standard error estimates were used to estimate hazard ratios (HR) for assessment of outcomes while controlling for covariates. Results of univariate and multivariate analyses of the total sample (HR, 0.97; 95% confidence interval [CI], 0.62-1.53; p = 0.86), massive transfusion sample (HR, 0.84; 95% CI, 0.46-1.56; p = 0.51), propensity-matched sample (HR, 0.68; 95% CI, 0.27-1.73; p = 0.34), and US/NATO military sample (HR, 0.76; 95% CI, 0.30-1.92; p = 0.48) indicate no statistically significant association between TXA use and mortality. Use of TXA was associated with increased risk of pulmonary embolism in the total sample (HR, 2.82; 95% CI, 2.08-3.81; p < 0.001), massive transfusion sample (HR, 3.64; 95% CI, 1.96-6.78; p = 0.003), US/NATO military sample (HR, 2.55; 95% CI, 1.73-3.69; p = 0.002), but not the propensity-matched sample (HR, 3.36; 95% CI, 0.80-14.10; p = 0.10). TXA was also associated with increased risk of deep vein thrombosis in the total sample (HR, 2.00; 95% CI, 1.21-3.30; p = 0.02) and US/NATO military sample (HR, 2.18; 95% CI, 1.20-3.96; p = 0.02). In the largest study on TXA use in a combat trauma population, TXA was not significantly associated with mortality, due to lack of statistical power. However, our HR estimates for mortality among patients who received TXA are consistent with previous findings from the CRASH-2 trial. At the same time, continued scrutiny and surveillance of TXA use in military trauma, specifically for prevention of thromboembolic events, is warranted. Therapeutic, level IV.

Low dose tranexamic acid reduces blood transfusion rate after total knee arthroplasty: A population-based study in Taiwan.

Previous reports, mostly small clinical trials conducted in USA or Europe, indicated that tranexamic acid (TXA) would be effective for reducing blood transfusions after total knee arthroplasty (TKA). However, large scale studies are needed regarding the effectiveness and safety issue of complication events following TKA, especially for the Asian population. We aimed to evaluate the efficacy and safety of TXA use based on data from an elderly population in Taiwan. This was a retrospective population-based study using an inpatient dataset from the nationwide health insurance research database in Taiwan. Patients aged >65years with a diagnosis of osteoarthritic knee in 2012 were included (n=10,321). A low-dose intravenous form of TXA (250-1000mg) was identified perioperatively during the TKA. The surgical outcomes of interest were allogeneic red blood cell transfusion and postoperative 30-day complications. A total of 1205 (11.7%) patients received TXA. Based on a multilevel logistic regression model, we found a 47% odds reduction of blood transfusion without elevating the complications of infection and vascular-related diseases. Furthermore, the drug effect in reducing transfusion was different among hospital levels, and medical centers had a relatively lower transfusion rate. The use of perioperative TXA was an efficient strategy to prevent blood loss after TKA.

Practical issues for the use of tranexamic acid in total knee arthroplasty: a systematic review

This systematic review was undertaken to answer three specific questions relating to the clinical values of tranexamic acid (TNA) in total knee arthroplasty (TKA): (1) Whether there are differences in blood-saving effects between the systemic and topical administrations; (2) Whether blood-saving effects of TNA differ by doses and timings of administration; and (3) Whether the use of TNA is safe at all reported doses, timings, and routes of administration with respect to the incidences of symptomatic deep-vein thrombosis (DVT) and pulmonary embolism (PE). A systematic review was carried out with 28 randomised controlled trials to evaluate the efficacy and safety of TNA use in TKA identified from the literature. Both systemic and topical administrations reduced blood loss after TKA, but transfusion reducing effects varied in studies whether systemic or topical administrations. The effects of TNA were influenced by doses and timings of administration. No increased incidences of symptomatic DVT and PE were found for all reported doses, timings, and routes of TNA administration. Surgeons can consider incorporating the use of TNA to their blood-saving protocols in TKA without serious concern of adverse events but need to adopt optimal doses, timings, and routes of TNA administrations.

Poster 77: The Inconsistency Spectrum of Wavefront Analysis

Previous reports, mostly small clinical trials conducted in USA or Europe, indicated that tranexamic acid (TXA) would be effective for reducing blood transfusions after total knee arthroplasty (TKA). However, large scale studies are needed regarding the effectiveness and safety issue of complication events following TKA, especially for the Asian population. We aimed to evaluate the efficacy and safety of TXA use based on data from an elderly population in Taiwan.This was a retrospective population-based study using an inpatient dataset from the nationwide health insurance research database in Taiwan. Patients aged >65 years with a diagnosis of osteoarthritic knee in 2012 were included (n = 10,321). A low-dose intravenous form of TXA (250–1000 mg) was identified perioperatively during the TKA. The surgical outcomes of interest were allogeneic red blood cell transfusion and postoperative 30-day complications.A total of 1205 (11.7%) patients received TXA. Based on a multilevel logistic regression model, we found a 47% odds reduction of blood transfusion without elevating the complications of infection and vascular-related diseases. Furthermore, the drug effect in reducing transfusion was different among hospital levels, and medical centers had a relatively lower transfusion rate.The use of perioperative TXA was an efficient strategy to prevent blood loss after TKA.