Efficacy and safety of tranexamic acid on blood loss and seizures in patients undergoing meningioma resection: A systematic review and meta-analysis.

INTRODUCTION: It is unclear how tranexamic acid (TXA) affects blood loss and seizures in meningioma resections. We performed a systematic review and meta-analysis and tried to evaluate the effectiveness and safety of TXA use for patients undergoing meningioma resections. METHODS: Regards to this systematic review and meta-analysis (registered with CRD42023416693), we searched PubMed, Embase (Ovid), EBSCO, and Cochrane central library up to and including Oct 2023. Patients undergoing meningioma resections treated with TXA and placebo or no treatment were eligible for this study. This would allow delineation of the impact of TXA on blood loss, postoperative seizure, and other complication incidences. RESULTS: Four prospective cohort studies with 781 patients (390 patients in the TXA group and 391 patients in the control group) were conducted via a systematic review and meta-analysis. The results suggested that the application of TXA for patients undergoing meningioma resections reduced mean blood loss of 252 mL with 95% confidence interval (CI) -469.26 to -34.67 (P = 0.02) and I2 of 94% but did not increase postoperative seizure (risk ratio: 1.08; 95%CI: 0.54 to 2.15; P = 0.84) and other complication rates. CONCLUSIONS: This systematic review and meta-analysis suggests that the administration of TXA could reduce blood loss in patients undergoing intracerebral meningioma resection. REGISTRY INFORMATION: The systematic review protocol has been registered at PROSPERO (Registration No. CRD42023416693) on April 23, 2023.

Intravenous versus topical tranexamic acid in spinal surgery: a systematic review and meta-analysis.

BACKGROUND: The administration of tranexamic acid (TXA) during spinal surgery has been shown to reduce blood loss. However, the efficacy and safety of intravenous TXA (ivTXA) and topical TXA (tTXA) are poorly documented. The present meta-analysis aimed to compare the efficacy and safety of ivTXA and tTXA administration in spinal surgery. METHODS: Potentially relevant academic articles were identified from PubMed, Ovid, Cochrane Library, CNKI database, and Wanfang Data from the date of inception until March 1, 2024. Randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) were included in our meta-analysis if they compared the efficacy and safety of ivTXA versus tTXA administration during spinal surgery. Secondary sources were identified from the references of the included literature. The meta-analysis was performed in accordance with the guidelines of the Cochrane Reviewer's Handbook and the PRISMA statement. Data were summarized using RevMan 5.3 software from Denmark. RESULTS: Four RCTs and one non-RCT met our inclusion criteria. The pooled outcomes demonstrated that ivTXA groups compared with tTXA groups had significantly less amount of total blood loss [weighted mean difference (WMD)=-159.55, 95% CI (-181.91,-137.19), P < 0.00001], hidden blood loss [WMD=-132.27, 95% CI (-159.81, -104.72), P < 0.00001], intraoperative blood loss [WMD=-86.22, 95% CI (-99.13, -73.31), P < 0.00001, I2 = 96%], and more high postoperative hemoglobin level [WMD = 8.96, 95% CI (5.18, 12.75), P < 0.00001, I2 = 29%], and less transfusion rate [risk ratio (RR) = 1.11, 95% CI (0.81,1.52), P = 0.50, I2 = 94%]. The pooled results showed no significant difference in thromboembolic events (deep venous thrombosis and pulmonary embolism) between the two groups. CONCLUSION: Our meta-analysis demonstrated that ivTXA was more effective than tTXA in inducing hemostatic effect during spinal surgery. However, the risk of a thrombotic event was not different between the two administration methods of TXA. More high quality RCTs are needed to further confirm our conclusions.

Efficacy of tranexamic acid versus placebo in reducing blood loss during burn excisional surgery: a multi-center, double-blind, parallel, randomized placebo-controlled clinical trial (TRANEX).

BACKGROUND: Despite an increase in knowledge, blood loss during burn excisional surgery remains a major challenge and is an independent predictor of mortality. During burn surgery, limited measures are available to control the bleeding. Increased fibrinolysis could be one of the contributing factors of blood loss during burn excisional surgery. Tranexamic acid inhibits the fibrinolytic response, and a small body of evidence shows positive effects of tranexamic acid on the volume of blood loss. METHODS: The main objectives of this study are twofold, (1) to investigate whether tranexamic acid reduces blood loss and (2) to investigate the changes in coagulation after burn trauma and during burn excisional surgery. This study is a multicenter double-blind randomized clinical trial in patients scheduled for burn excisional surgery within the Dutch burn centers. All adult patients scheduled for burn surgery with an expected blood loss of ≥ 250 are eligible for inclusion in this study. The study is powered on a blood loss reduction of 25% in the intervention group. In total, 95 subjects will be included. The intervention group will receive 1500 mg tranexamic acid versus placebo in the other group. Primary endpoint is reduction of blood loss. Secondary endpoints include occurrence of fibrinolysis during surgery, graft take of the split skin graft, and differences in coagulation and blood clot formation. DISCUSSION: This protocol of a randomized controlled trial aims to investigate the efficacy of tranexamic acid in reducing blood loss during burn excisional surgery. Furthermore, this study aims to clarify the coagulation status after burn trauma and during the surgical process. TRIAL REGISTRATION: EudraCT: 2020-005405-10; ClinicalTrial.gov: NCT05507983 (retrospectively registered in August 2022, inclusion started in December 2021).

Tranexamic acid efficacy in geriatric hip fractures: impact of nutritional status on blood loss, transfusion rates, and safety.

BACKGROUND: Tranexamic acid (TXA) is a widely employed intervention in orthopedic surgeries to minimize blood loss and the need for postoperative transfusions. This study focuses on assessing the efficacy and safety of TXA specifically in undernourished older adults undergoing hip fracture procedures. METHODS: A total of 216 patients were classified into two groups based on the Geriatric Nutritional Risk Index: undernourished and normal. In total, 82 patients received intravenous TXA at a dosage of 15 mg/kg before incision, with an additional 1 g administered intravenously over a 3-hour period postoperatively. Postoperative hemoglobin (Hb) drop, blood transfusion rate, and the incidence of deep venous thrombosis (DVT) were assessed in each group according to the presence or absence of TXA. Additionally, demographic factors including age, sex, body mass index, and serum albumin were investigated. RESULTS: 51.9% patients were identified as undernourished, experiencing progressive anemia (Hb: 10.9 ± 1.5 g/dL) and hypoalbuminemia (serum albumin: 31.9 ± 8 g/L). In comparison with the normal group, undernourished individuals were more likely to sustain femoral neck fractures (undernutrition vs. normal: 56.2 vs. 42.3%) and less likely to incur trochanteric fractures (undernutrition vs. normal: 43.8 vs. 57.7%) (P = 0.043). TXA administration significantly reduced the transfusion rate (P = 0.014) and Hb drop (P = 0.001) in the normal nutritional group, while its impact on the undernourished group remained less pronounced. There was no significant association between TXA administration and the rate of DVT complications, irrespective of the nutritional status. CONCLUSIONS: Undernutrition not only diminishes muscle strength and gait function, leading to various types of hip fractures, but it may also hinder the efficacy of TXA in reducing blood transfusion rates and blood loss.

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.

Evaluation of the Safety of Uninterrupted Warfarin Anticoagulation With Tranexamic Acid in Total Joint Arthroplasty.

BACKGROUND: The continuation of long-term warfarin therapy is gaining acceptance in minor surgeries but maintaining therapeutic international normalized ratio (INR) values among patients during major orthopedic procedures raises concern. While bridging therapy with low-molecular-weight heparin is currently recommended for patients receiving anticoagulation, few studies have evaluated the safety of continuing warfarin during total joint arthroplasty. This study evaluated the safety and efficacy of continuous warfarin anticoagulation through total joint arthroplasty with and without prophylactic tranexamic acid (TXA). MATERIALS AND METHODS: We conducted a retrospective, matched-pair analysis of two experimental groups of patients who underwent primary total hip arthroplasty or total knee arthroplasty performed by a single surgeon. Our first experimental group, warfarin plus TXA (warfarin+TXA), consisted of 21 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) and who received prophylactic TXA. Our second experimental group, warfarin without TXA (warfarin-TXA), consisted of 40 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) without prophylactic TXA. RESULTS: The percent change in hemoglobin value after surgery, red blood cells transfused, surgical site infections, bleeding complications, and thrombotic complications were similar between both experimental and control groups. When comparing the historical group with the warfarin+TXA group, the addition of TXA resulted in a statistical decrease in mean red blood cells transfused and estimated blood loss, with no statistically significant increase in complications. CONCLUSION: Many factors must be considered when choosing perioperative thromboembolic prophylaxis for arthroplasty candidates with medical comorbidities requiring long-term anticoagulation. This study presents data indicating that it could be safe and effective to continue therapeutic warfarin while using prophylactic TXA. [Orthopedics. 2024;47(4):211-216.].

Tranexamic acid in trauma: After 3 hours from injury, when is it safe and effective to use again?

Tranexamic acid (TXA) has proven mortality benefit if used early after traumatic injury, likely related to a combination of bleeding reduction and other non-bleeding effects. If TXA is given more than 3 h after traumatic injury, there is a significant and paradoxical increased risk of death due to bleeding. TXA has level 1 evidence for use as a bleeding reduction agent in isolated orthopedic operations, but in polytrauma patients undergoing orthopedic operations, it is not clear if and when TXA is safe or effective once outside the 3-h window of proven trauma efficacy.

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.

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.

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

BACKGROUND: Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. METHODS: We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. RESULTS: Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). CONCLUSIONS: Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

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 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.