Efficacy, Safety, Satisfaction, Adherence to Treatment With Nano-Formulated Cysteamine Tranexamic Acid Cream to Treat Melasma.

BACKGROUND: Melasma is a chronic pigmentary disorder. In this study, an innovative cream combining cysteamine and tranexamic acid (TXA) was assessed. OBJECTIVE: To evaluate the safety, efficacy, and patient satisfaction of a novel nano-formulated cysteamine and TXA combination cream in treating subjects with epidermal melasma. METHODS:   Fifty (50) randomized subjects participated and received cysteamine and TXA combination cream. The cream was applied for 30 minutes daily for a 3-month duration. Treatment effectiveness, safety, patient satisfaction, and adherence were evaluated. RESULTS: A continuous improvement in melasma was observed, with modified Melasma Area and Severity Index (mMASI) scores improving by 40%, 57%, and 63% at 30, 60, and 90 days, respectively. The primary endpoint of a decrease in mMASI scores was met, with 91% of participants experiencing melasma improvement. Patient Satisfaction and Patient Adherence scores indicated satisfaction. Convenience exhibited the strongest correlation with patient adherence.  Conclusion: Nano-formulated cysteamine and TXA combination cream showed significant efficacy in decreasing mMASI score while demonstrating a strong safety profile and patient satisfaction.  J Drugs Dermatol. 2024;23(7):529-537.     doi:10.36849/JDD.7765R1.

The necessity of suction drainage when intra-articular injection of tranexamic acid is used during primary total knee arthroplasty: a retrospective study.

BACKGROUND: Suction drainages are commonly used after total knee arthroplasty (TKA) procedures; however, their use is somewhat controversial. Recently, some reports have claimed that the administration of tranexamic acid (TXA) may prevent postoperative bleeding following TKAs. Although numerous studies have reported regarding different dosages, timings of administration, or drain clamping times for intravenous and intra-articular TXA injections (IA-TXAs), few have examined whether suction drainage is necessary when TXA is administered. In this study, we compared using suction drainage without TXA administration and IA-TXA without suction drainage and aimed to examine the need for suction drainage during IA-TXA. METHODS: This retrospective study was conducted on 217 patients who had received TKA for osteoarthritis; 104 were placed on suction drainage after TKA without TXA (Group A), whereas the remaining 113 received IA-TXA immediately after surgery without suction drainage (Group B). Our clinical evaluation included assessments of the need for transfusion, presence of postoperative complications, incidence of deep vein thrombosis (DVT), and changes in hemoglobin (Hb), hematocrit (Hct), and D-dimer levels. RESULTS: No significant differences were observed in terms of postoperative complications and preoperative Hb, Hct, or D-dimer levels between the two groups. Although the prevalence of DVT was significantly higher in Group B (p < 0.05), all cases were asymptomatic. Hb and Hct levels were significantly lower in Group A than in Group B at 1, 3, 7, and 14 days postoperatively (p < 0.05), although none of the cases required blood transfusions. D-dimer levels were significantly higher in Group A than in Group B at 1 and 3 days postoperatively (p < 0.05). CONCLUSION: Suction drainage might not be necessary when IA-TXA is administered after TKA procedures.

Efficacy and safety of intravenous tranexamic acid in microscopic modified radical mastoidectomy: a study protocol for a prospective, randomised, double-blind controlled trial.

INTRODUCTION: Radical mastoidectomy is a common procedure for chronic suppurative otitis media, typically performed under a microscope. The smooth operation is closely related to the clarity of the operative field. Our trial is designed to investigate whether the intravenous administration of tranexamic acid (TXA) can improve the clarity of the operative field, reduce the operative time, and increase surgeon satisfaction. METHODS AND ANALYSIS: This study is a prospective, randomised, double-blinded, controlled trial that aims to investigate the effects of TXA on patients with otitis media. The trial will include patients between the ages of 18 and 65 who will be randomly assigned to either the TXA group or the control group. In the TXA group, patients will receive 1 g of TXA diluted to 20 mL of normal saline before anaesthesia induction while the control group will receive 20 mL of normal saline. The primary outcome measure will be the Modena Bleeding Score, which will assess the clarity of the surgical field. Secondary outcomes will include the surgeon's satisfaction with surgical conditions, operation time, laboratory measurements (prothrombin time, activated partial thromboplastin time, fibrin degradation products, D-dimer) and levels of inflammatory factors (such as IL-6) at 24 hours postoperatively. In addition, the incidence of general adverse reactions such as postoperative nausea, vomiting and dizziness; serious adverse events such as arterial and venous thromboembolism, myocardial infarction and epilepsy within 90 days will be compared between the two groups. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee of Peking University People's Hospital (2021PHB173-001), on 19 July 2021. The trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100049183.

Efficacy and safety of tranexamic acid in patients undergoing thoracic surgery: a systematic review and PRISMA-compliant meta-analysis

OBJECTIVES: Perioperative bleeding poses a significant issue during thoracic surgery. Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. The purpose of the current study was designed to investigate the efficacy and safety of TXA in patients undergoing thoracic surgery. METHODS: An extensive search of PubMed, Web of Science (WOS), Cochrane Library (trials), Embase, OVID, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP electronic databases was performed to identify studies published between the inception of these databases and March 2023. The primary outcomes included perioperative blood loss and blood transfusions. Secondary outcomes of interest included the length of stay (LOS) in hospital and the incidence of thromboembolic events. Weighted mean differences (WMDs) or odds ratios (OR) with 95% confidence intervals (CI) were used to determine treatment effects for continuous and dichotomous variables, respectively. RESULTS: Five qualified studies including 307 thoracic surgical patients were included in the current study. Among them, 65 patients were randomly allocated to the group receiving TXA administration (the TXA group); the other 142 patients were assigned to the group not receiving TXA administration (the control group). TXA significantly reduced the quantity of hemorrhage in the postoperative period (postoperative 12h: WMD = -81.90 ml; 95% CI: -139.55 to -24.26; P = 0.005; postoperative 24h: WMD = -97.44 ml; 95% CI: -121.44 to -73.44; P< 0.00001); The intraoperative blood transfusion volume (WMD = -0.54 units; 95% CI: -1.06 to -0.03; P = 0.04); LOS in hospital (WMD = -0.6 days; 95% CI: -1.04 to -0.16; P = 0.008); And there was no postoperative thromboembolic event reported in the included studies. CONCLUSIONS: The present study demonstrated that TXA significantly decreased blood loss within 12 and 24 hours postoperatively. A qualitative review did not identify elevated risks of safety outcomes such as thromboembolic events. It also suggested that TXA administration was associated with shorter LOS in hospital as compared to control. To validate this further, additional well-planned and adequately powered randomized studies are necessary.

Efficacy and safety of the combination of oral tranexamic acid and intense pulsed light versus oral tranexamic acid alone in the treatment of refractory Riehl's melanosis: A prospective, comparative study.

BACKGROUND: There is no standardized and effective treatment modality for Riehl's melanosis. AIMS: To compare the efficacy and safety of oral tranexamic acid (TXA) combined with intense pulsed light (IPL) versus TXA alone in the treatment of refractory Riehl's melanosis. METHODS: A prospective study of 28 subjects with refractory Riehl's melanosis and Fitzpatrick Skin Types III or IV was conducted. All subjects received oral TXA 500 mg daily and 11 of them were treated in combination with monthly IPL therapy for 6 months. The primary outcome measure was mean melanin index (MI), erythema index (EI) and acquired dermal macular hyperpigmentation area and severity index (DPASI). The Physician Global Assessment (PGA) and patient satisfaction scale were documented. RESULTS: After treatment, DPASI, mean MI, and EI were significantly reduced in both groups. The group treated with combination therapy showed better improvement according to MI (p = 0.0032) and DPASI (p = 0.00468). PGA and patient satisfaction scale showed superior efficacy in the combination group. No significant difference was observed in treatment-related side effects. CONCLUSION: The combination of oral TXA and IPL proves to be a safe and satisfactory treatment strategy for refractory Riehl's melanosis.

Efficacy and tolerability of a depigmenting gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that targets the biological processes regulating skin melanogenesis.

BACKGROUND: The diverse causes of hyperpigmentation and complex nature of melanogenesis make it a challenge to manage. Current approaches either fail to deliver effective pigmentation control or have undesirable safety profiles that preclude their long-term use. AIMS: To evaluate the capacity of a cosmetic gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that was designed to target the biological processes regulating skin melanogenesis to attenuate melanin production in vitro and reduce hyperpigmentation clinically. METHODS: Capacity to reduce melanin production in vitro was determined in melanocyte-containing reconstructed human epidermis (RHEm). Clinical efficacy and skin tolerability following twice daily application were assessed in 35 subjects with slight to moderate facial hyperpigmentation by instrumental (VISIA®-CR, Mexameter®) and clinical (mMASI, clinical score, IGA for hyperpigmentation) evaluation on D14, D28, D56, and D84. Maintenance of pigmentation control was followed up 1 month after cessation of treatment on D112. RESULTS: In RHEm in vitro, melanin production was reduced by 50.0% from baseline (D0) on D14 (p < 0.001) and by 67.0% on D21 (p < 0.001). Clinical reductions from baseline in brown spots count (-9.0%; p < 0.05), brown spots area (-16.7%; p < 0.001), and the melanin index (-11.4%; p < 0.001) were observed within 14 days of use. Statistically significant improvements in all clinical parameters were achieved by D28. By the end of treatment on D84, the number and surface area of brown spots were reduced by 28.4% and 40.3% compared to D0, respectively (p < 0.001, both), the melanin index was reduced by 31.1% (p < 0.001), mMASI was reduced by 63.0% (p < 0.001), and skin luminosity was increased by 79.0% (p < 0.001). IGA was reduced from 2.3 on D0 to 1.3 on D84 (p < 0.001). Improvements to all these parameters were maintained until D112, 1 month after termination of treatment. The product also demonstrated very good skin tolerability. CONCLUSION: A gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, and hydroxy acids, designed to target the biological processes regulating skin melanogenesis, demonstrates rapid, robust, and sustained pigmentation control in this cohort.

Analysis of tranexamic acid usage in adult spinal deformity patients with relative contraindications: does it increase the risk of complications?

OBJECTIVE: Complex spinal deformity surgeries may involve significant blood loss. The use of antifibrinolytic agents such as tranexamic acid (TXA) has been proven to reduce perioperative blood loss. However, for patients with a history of thromboembolic events, there is concern of increased risk when TXA is used during these surgeries. This study aimed to assess whether TXA use in patients undergoing complex spinal deformity correction surgeries increases the risk of thromboembolic complications based on preexisting thromboembolic risk factors. METHODS: Data were analyzed for adult patients who received TXA during surgical correction for spinal deformity at 21 North American centers between August 2018 and October 2022. Patients with preexisting thromboembolic events and other risk factors (history of deep venous thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], stroke, peripheral vascular disease, or cancer) were identified. Thromboembolic complication rates were assessed during the postoperative 90 days. Univariate and multivariate analyses were performed to assess thromboembolic outcomes in high-risk and low-risk patients who received intravenous TXA. RESULTS: Among 411 consecutive patients who underwent complex spinal deformity surgery and received TXA intraoperatively, 130 (31.6%) were considered high-risk patients. There was no significant difference in thromboembolic complications between patients with and those without preexisting thromboembolic risk factors in univariate analysis (high-risk group vs low-risk group: 8.5% vs 2.8%, p = 0.45). Specifically, there were no significant differences between groups regarding the 90-day postoperative rates of DVT (high-risk group vs low-risk group: 1.5% vs 1.4%, p = 0.98), PE (2.3% vs 1.8%, p = 0.71), acute MI (1.5% vs 0%, p = 0.19), or stroke (0.8% vs 1.1%, p > 0.99). On multivariate analysis, high-risk status was not a significant independent predictor for any of the thromboembolic complications. CONCLUSIONS: Administration of intravenous TXA during the correction procedure did not change rates of thromboembolic events, acute MI, or stroke in this cohort of adult spinal deformity surgery patients.

Kidney disease in trials of perioperative tranexamic acid.

STUDY OBJECTIVE: To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023. PATIENTS: Patients undergoing non-obstetric surgery. INTERVENTIONS: Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid. MEASUREMENT: We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function. MAIN RESULTS: We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min. CONCLUSIONS: The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.

Use of Aprotinin versus Tranexamic Acid in Cardiac Surgery Patients with High-Risk for Excessive Bleeding (APACHE) trial: a multicentre retrospective comparative non-randomized historical study.

OBJECTIVES: Following the reintroduction of aprotinin into the European market, the French Society of Cardiovascular and Thoracic Anaesthesiologists recommended its prophylactic use at half-dose for high-risk cardiac surgery patients. We examined whether the use of aprotinin instead of tranexamic acid could significantly reduce severe perioperative bleeding. METHODS: This multicentre, retrospective, historical study included cardiac surgery patients treated with aprotinin or tranexamic acid between December 2017 and September 2020. The primary efficacy end point was the severe or massive perioperative bleeding (class 3-4 of the universal definition of perioperative bleeding). The safety secondary end points included the occurrence of thromboembolic events and all-cause mortality within 30 days after surgery. RESULTS: Among the 693 patients included in the study, 347 received aprotinin and 346 took tranexamic acid. The percentage of patients with severe or massive bleeding was similar in the 2 groups (42.1% vs 43.6%, Adjusted odds ratio [ORadj] = 0.87, 95% confidence interval: 0.62-1.23, P = 0.44), as was the perioperative need for blood products (81.0% vs 83.2%, ORadj = 0.75, 95% confidence interval: 0.48-1.17, P = 0.20). However, the median (Interquartile range) 12 h postoperative blood loss was significantly lower in the aprotinin group (383 ml [241-625] vs 450 ml [290-730], P < 0.01). Compared to tranexamic acid, the intraoperative use of aprotinin was associated with increased risk for thromboembolic events (adjusted Hazard ratio 2.30 [95% Cl: 1.06-5.30]; P = 0.04). CONCLUSIONS: Given the modest reduction in blood loss at the expense of a significant increase in thromboembolic adverse events, aprotinin use in high-risk cardiac surgery patients should be based on a carefully considered benefit-risk assessment.

Life-Threatening Subglottic Thrombus Formation after Administration of Nebulized Tranexamic Acid.

We present a case of subglottic thrombus formation after administration of nebulized tranexamic acid (TXA) for postoperative hemoptysis following CO2 laser wedge excision of subglottic stenosis. Although other factors certainly could have resulted in postoperative bleeding and subsequent thrombus formation, the patient's rapid decompensation following administration of nebulized TXA suggests a direct effect. We recommend implementing an airway action plan regarding TXA use for patients presenting to the emergency department with postoperative hemorrhage following otolaryngology procedures. Laryngoscope, 134:1356-1358, 2024.

The Efficacy and Safety of a Low-Dose Tranexamic Acid Bolus-Only Protocol Compared with the Moderate-Dose Protocol in Valvular Heart Surgery.

In 873 propensity score-matched pairs of patients undergoing valvular heart surgery, we compared a "moderate dose" of tranexamic acid (TXA) protocol (group 1; median TXA dose: 24 mg/kg body weight) with a 1.5-g "bolus-only" protocol (group 2; median TXA dose: 19 mg/kg body weight). The number of transfused patients was higher in group 2 than in group 1 (74.5 vs 66.0%, p < 0.001), as was the number of transfused red blood cell concentrates (p = 0.001). The risks of re-exploration and convulsive seizures were similar between groups (p > 0.50). Data indicate an impaired efficacy following the "bolus-only" protocol, without a significant safety improvement.

The effects of tranexamic acid on platelets in patients undergoing cardiac surgery: a systematic review and meta-analysis.

This meta-analysis was designed to evaluate the effects of tranexamic acid (TXA) on platelets in patients undergoing cardiac surgery (CS). Relevant trials were identified by computerized searches of PUBMED, Cochrane Library, EMBASE, OVID, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP Data till Jun 4th, 2022, were searched using search terms "platelet", "Tranexamic acid", "cardiac surgery", "randomized controlled trial" database search was updated on Jan 1st 2023. Primary outcomes included platelet counts, function and platelet membrane proteins. Secondary outcome included postoperative bleeding. Search yielded 49 eligible trials, which were finally included in the current study. As compared to Control, TXA did not influence post-operative platelet counts in adult patients undergoing on- or off-pump CS, but significantly increased post-operative platelet counts in pediatric patients undergoing on-pump CS [(WMD = 16.72; 95% CI 6.33 to 27.10; P = 0.002)], significantly increased post-operative platelet counts in adults valvular surgery [(WMD = 14.24; 95% CI 1.36 to 27.12; P = 0.03). Additionally, TXA improved ADP-stimulated platelet aggression [(WMD = 1.88; 95% CI 0.93 to 2.83; P = 0.0001)] and improved CD63 expression on platelets [(WMD = 0.72; 95% CI 0.29 to 1.15; P = 0.001)]. The current study demonstrated that TXA administration did not affect post-operative platelet counts in adult patients undergoing either on- or off-pump CABG, but significantly increased post-operative platelet counts in pediatric patients undergoing on-pump CS and adults valvular surgery. Furthermore, TXA improved ADP-stimulated platelet aggression and improved CD63 expression on platelets. To further confirm this, more well designed and adequately powered randomized trials are needed.

Tranexamic Acid Is Safe in Patients with a History of Venous Thromboembolism Undergoing Total Joint Arthroplasty.

BACKGROUND: Tranexamic acid (TXA) is increasingly utilized during total knee arthroplasty (TKA) and total hip arthroplasty (THA) to decrease blood loss; however, there are concerns with regard to potential thromboembolic complications, particularly in high-risk patients. This study sought to define a subset of patients at elevated risk for thromboembolic complications following total joint arthroplasty (TJA) and to compare postoperative outcomes between patients who received TXA and those who did not. METHODS: Patients who underwent primary, elective TJA from 2015 to 2021 were identified in the Premier Healthcare Database. Patients with a history of venous thromboembolism, defined as a history of pulmonary embolism or deep vein thrombosis, were identified and formed the high-risk cohort. Patient demographic characteristics, hospital factors, patient comorbidities, antithrombotic medication use, perioperative blood transfusion, and 90-day complications were assessed and compared between patients who received TXA and those who did not. Univariate regression and multivariable regression were performed to account for potential confounders. RESULTS: The high-risk cohort comprised 70,759 patients who underwent TJA, of whom 46,074 (65.1%) received TXA and 24,685 (34.9%) did not. After controlling for confounding factors, patients in the TXA cohort had similar risks of pulmonary embolism (adjusted odds ratio [OR], 0.90 [95% confidence interval (CI), 0.79 to 1.02]; p = 0.097), stroke (adjusted OR, 0.97 [95% CI, 0.69 to 1.37]; p = 0.867), and myocardial infarction (adjusted OR, 0.93 [95% CI, 0.69 to 1.24]; p = 0.614) compared with patients who did not receive TXA. Patients who received TXA demonstrated decreased risks of transfusion (adjusted OR, 0.42 [95% CI, 0.38 to 0.46]; p < 0.001) and 90-day readmission (adjusted OR, 0.87 [95% CI, 0.80 to 0.94]; p < 0.001). CONCLUSIONS: TXA utilization was not associated with an increased risk of postoperative pulmonary embolism, stroke, or myocardial infarction in patients with a history of venous thromboembolism. Furthermore, patients who received TXA had a decreased risk of transfusion and readmission. This evidence suggests that TXA may be safely utilized among select high-risk patients. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

When to use tranexamic acid for the treatment of major bleeding?

Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15 years, there has been accumulating evidence on the use of TXA for the treatment of active bleeding in a variety of clinical contexts. Clinical trials have shown that the efficacy and safety of TXA for the treatment of bleeding differ according to the clinical context in which it is being administered, timing of administration, and dose. Early administration is important for efficacy, particularly in trauma and PPH. Further studies are needed to understand the mechanisms by which TXA provides benefit, optimal modes of administration and dosing, and its effect in some clinical settings, such as spontaneous intracerebral hemorrhage. There is no evidence that TXA increases the risk of thrombotic events in patients with major bleeding overall. However, there is evidence of increased risk of venous thrombosis in patients with gastrointestinal bleeding. There is also evidence of increased risk of seizures with the use of higher doses. This review summarizes the current evidence for the use of TXA for patients with active bleeding and highlights the importance of generating evidence of efficacy and safety of hemostatic interventions specific to the bleeding contexts-as findings from 1 clinical setting may not be generalizable to other contexts-and that of individual patient assessment for bleeding, thrombotic, and other risks, as well as important logistical and other practical considerations, to optimize care and outcomes in these settings.

The efficacy and safety of tranexamic acid utilization in total ankle arthroplasty: a systematic review and meta-analysis.

INTRODUCTION: There is still a lack of information on the role of Tranexamic acid (TXA) in total ankle arthroplasty (TAA). The purpose of this study is to comprehensively review, consolidate, and analyze findings from existing research on the effectiveness and safety of TXA in TAA. MATERIALS AND METHODS: The comprehensive literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using PubMed, Embase, Web of Science, and Cochrane databases, for original, English-language studies investigating the efficacy and safety of TXA in TAA, through February 2023. Evaluated data for the meta-analysis included estimated blood loss (EBL), change in perioperative hemoglobin, need for transfusion, and complications including DVT/PE, and wound complications. RESULTS: A total of nine studies were included in this study. In total, 450 TAA were included, with 244 receiving TXA (54.2%) and 206 not receiving TXA (45.8%). TXA in TAA significantly decreased EBL. A significantly lower rate of wound complications in the TXA group with the relative risk (RR) of 0.51. We classified wound complications into wound infection and delayed wound healing/dehiscence. A significant decrease in the rate of wound infection and a tendency showing a decrease in the rate of delayed wound healing/dehiscence in the TXA group were noted: the RR of 0.29, and 0.63, respectively. TXA did not increase the incidence of DVT/PE following TAA. CONCLUSIONS: In conclusion, the utilization of TXA during TAA demonstrated a statistically significant reduction in EBL and relative risk for wound complications. However, further RCTs with larger sample sizes will be necessary to establish a more robust conclusion regarding the efficacy and safety of TXA in TAA. LEVEL OF EVIDENCE: Level III, systematic review and meta-analysis.