Patient sex and use of tranexamic acid in liver transplantation.

Background: Differences in medical treatment between women and men are common and involve out-of-hospital emergency care, the intensity of pain treatment, and the use of antifibrinolytic treatment in emergency trauma patients. If woman and man receive different antifibrinolytic treatment in highly-standardized major transplant surgery is unknown. Methods: We conducted a retrospective cohort study on patients who underwent liver transplantation at Heidelberg University Hospital, Heidelberg, Germany between 2004 and 2017. Logistic regression analyses were performed to determine if sex is associated with the administration of TXA during liver transplantation. Secondary endpoints included venous thrombotic complications, graft failure, mortality, myocardial infarction, hepatic artery thrombosis, and stroke within the first 30 days after liver transplant as well as length of hospital stay and length of intensive care unit stay. Results: Out of 779 patients who underwent liver transplantation, 262 patients received TXA. Female sex was not associated with intraoperative administration of TXA [adjusted OR: 0.929 (95% CI 0.654; 1.320), p = 0.681]. The secondary endpoints graft failure (13.2% vs. 8.4%, women vs. men, p = 0.039), pulmonary embolism (3.4% vs. 0.9%, women vs. men, p = 0.012), stroke (1.7% vs. 0.4%, women vs. men, p = 0.049), and deep vein thrombosis (0.8% vs. 0%, women vs. men, p = 0.031) within 30 days after liver transplantation were more frequent in women. Mortality, myocardial infarction, and other secondary endpoints did not differ between groups. However, in women, the use of TXA was associated with a lower rate in thromboembolic complications. Conclusion: Our data indicate that different from other scenarios with massive bleeding complications the administration of TXA during liver transplantation is not associated with sex. However, sex is associated with the risk for complications, and in woman TXA might have a preventive effect on the rate of thromboembolic complications. Reasons underlying the observed sex bias rate remain uncertain.

Impact of a Tranexamic Acid Dosing Practice Guideline in Reducing Blood Product Administration in Pediatric Scoliosis Surgery.

Pediatric patients who undergo spinal corrective surgery often require multiple blood product transfusions. The use of antifibrinolytics, especially tranexamic acid (TXA), to mitigate intraoperative blood loss has increased in popularity. The goal of this quality improvement project was to evaluate provider compliance with a TXA dosing protocol during pediatric corrective spine procedures. A retrospective chart review was conducted to compare pre- and postimplementation data on cell saver and packed red blood cell (PRBC) administration and dose of antifibrinolytic administered. A total of 486 patients (68% idiopathic and 32% neuromuscular) were evaluated over a 9-year period. Following implementation of the protocol, patients of idiopathic origin experienced a 20% reduction in cell saver administration, a 10% reduction in PRBC administration, and a 37% increase in provider compliance with the dosing protocol. Patients of neuromuscular origin experienced a 53% increase in provider compliance with the recommended TXA dosing protocol; however, this patient population did not experience a statistically significant reduction in transfusion requirements. Implementation of an antifibrinolytic protocol can facilitate compliance with recommended TXA dosing parameters and potentially decrease intraoperative blood loss, reducing blood product transfusion requirements.

The Impact of Tranexamic Acid on Blood Loss Management in Primary Total Knee Arthroplasty: A Comprehensive Review.

Total knee arthroplasty (TKA) is a widely performed surgical procedure to restore function and relieve pain in patients with advanced knee arthritis. One of the key challenges in TKA is managing perioperative blood loss, which can lead to complications such as postoperative anemia and the need for blood transfusions. Tranexamic acid (TXA), an antifibrinolytic agent, has shown promising results in reducing blood loss and transfusion requirements in various surgical settings, including TKA. This comprehensive review synthesizes current evidence regarding the efficacy and safety profile of TXA in primary TKA. Mechanistically, TXA functions by inhibiting the breakdown of fibrin clots, promoting hemostasis, and minimizing blood loss. Clinical studies evaluating TXA in TKA have consistently demonstrated significant reductions in blood loss parameters, including total blood loss, postoperative drain output, and transfusion rates. Key findings highlight the efficacy of TXA across different dosing regimens and administration routes, with minimal associated risks of thromboembolic events or adverse effects. Comparative analyses with other blood conservation strategies underscore TXA's superiority in reducing transfusion requirements and its cost-effectiveness in clinical practice. The review also discusses current clinical guidelines and recommendations for TXA use in TKA, emphasizing optimal dosing strategies and patient selection criteria. Future research directions include exploring the long-term outcomes of TXA administration and its impact on functional recovery, and refining protocols to enhance its efficacy and safety further. In conclusion, TXA represents a valuable adjunct in blood loss management during primary TKA, offering substantial benefits in patient outcomes, healthcare resource utilization, and cost-effectiveness. Continued research efforts are warranted to optimize its use and expand its applicability in orthopedic surgery.

Tranexamic acid use in sarcoma surgery patients: A systematic review and meta-analysis.

INTRODUCTION: Perioperative bleeding increases morbidity and mortality in sarcoma patients. Tranexamic acid (TXA), an antifibrinolytic, is widely utilized in non-sarcoma orthopaedic surgeries, but its adoption in sarcoma surgery is hindered by concerns about thrombotic events. METHODS: Searches in Ovid MEDLINE, EMBASE, and CENTRAL were performed without date restrictions. Inclusion criteria encompassed sarcoma patients undergoing surgery with TXA intervention. Two authors independently screened studies, resolved conflicts, and assessed biases. RESULTS: Eight studies met inclusion criteria, comprising 2142 patients. TXA administration varied in dose and timing across studies. Meta-analysis revealed significantly reduced mean blood loss with TXA of -462.5 mL ([95% confidence interval [CI: -596.7, -328.31], p < 0.001) but no difference in transfusion rates (odds ratio [OR] = 0.51 [95% CI: 0.14-1.89]) or venous thromboembolism events (OR = 0.93 [95% CI: 0.40, 2.16]). Study biases were predominantly moderate to high due to retrospective designs and lack of control for confounders. Quality of reporting varied, with limitations identified in outcome reporting and effect size estimation. CONCLUSIONS: Despite evidence of reduced blood loss, the absence of prospective studies limits conclusive recommendations on TXA use in sarcoma surgery. Further research is warranted to determine optimal TXA regimens and assess safety concerns regarding thrombotic events in this patient population.

Evaluating the Effectiveness of Tranexamic Acid vs. Placebo in Cardiac Surgery: A Systematic Review and Meta-Analysis.

Tranexamic acid (TXA), a potent antifibrinolytic agent, is widely used in cardiac surgical procedures worldwide to minimize surgical bleeding and reduce the need for perioperative blood transfusions. However, the use of TXA may increase the risk of coronary artery graft thrombosis, potentially leading to a higher occurrence of late thrombotic events. Some studies have suggested that drugs like TXA, aimed at decreasing bleeding during cardiac surgeries, may be associated with elevated risks of thrombotic complications or mortality. Conversely, the reduced need for blood transfusions could contribute to improved long-term outcomes. Thus, a systematic review and meta-analysis were undertaken to assess the efficacy of TXA in cardiac surgery patients. Searches were conducted in databases including PubMed and PubMed Central. Data were extracted, and their quality was assessed using the Cochrane risk of bias tool for randomized clinical trials (RCTs). A random effects model was used to compute the pooled prevalence and investigate heterogeneity using the I2 statistic. Subgroup analyses differentiated between experimental and placebo groups. Additionally, sensitivity analyses were performed to assess the robustness of the findings, and publication bias was examined. An overall sample size of 12,869 patients was included in the meta-analysis, derived from seven of the 10 selected articles. This pooled sample was used to conduct an analysis of TXA's efficacy in cardiac surgery patients. Subgroup analysis revealed a 95% heterogeneity and indicated a p-value of less than 0.05, favoring TXA over placebo in terms of better outcomes. Our research indicates a statistically significant relationship between the efficacy of TXA and the number of patients undergoing heart surgery. According to our findings, there is a pressing need to enhance this evidence base and conduct larger RCTs to better understand the benefits of using TXA, aiming to maintain a low risk of bleeding after both major and minor heart surgeries.

Unravelling the Antifibrinolytic Mechanism of Action of the 1,2,3-Triazole Derivatives.

A new family of antifibrinolytic drugs has been recently discovered, combining a triazole moiety, an oxadiazolone, and a terminal amine. Two of the molecules of this family have shown activity that is greater than or similar to that of tranexamic acid (TXA), the current antifibrinolytic gold standard, which has been associated with several side effects and whose use is limited in patients with renal impairment. The aim of this work was to thoroughly examine the mechanism of action of the two ideal candidates of the 1,2,3-triazole family and compare them with TXA, to identify an antifibrinolytic alternative active at lower dosages. Specifically, the antifibrinolytic activity of the two compounds (1 and 5) and TXA was assessed in fibrinolytic isolated systems and in whole blood. Results revealed that despite having an activity pathway comparable to that of TXA, both compounds showed greater activity in blood. These differences could be attributed to a more stable ligand-target binding to the pocket of plasminogen for compounds 1 and 5, as suggested by molecular dynamic simulations. This work presents further evidence of the antifibrinolytic activity of the two best candidates of the 1,2,3-triazole family and paves the way for incorporating these molecules as new antifibrinolytic therapies.

Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.

Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.

Comparison of coagulation and fibrinolysis in Irish Wolfhounds and age-matched control dogs using tissue plasminogen activator-augmented viscoelastic testing.

OBJECTIVE: To determine if Irish Wolfhounds (IWs), like other sighthounds, are hyperfibrinolytic compared with nonsighthound dogs using 2 native and tissue plasminogen activator (tPA)-enhanced viscoelastic assays, one that is whole blood-based (viscoelastic coagulation monitor [VCM]) and the other that is plasma-based thromboelastography (TEG). DESIGN: Cohort study. SETTING: University teaching hospital. ANIMALS: A convenience sample of 27 IWs recruited from the Irish Wolfhound Association of New England Specialty and the local community, and 27 healthy, age-matched, large-breed control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples including CBC, biochemistry, traditional coagulation, and viscoelastic testing were collected from IWs and control dogs. Twelve IWs had viscoelastic testing. IWs had lower fibrinogen concentrations (215.5 ± 57.8 vs 251.4 ± 64.5 mg/dL, P = 0.034) and formed weaker clots on both whole-blood VCM and plasma TEG assays (maximum clot firmness [VCM-MCF] = 39.4 [25.1-48.8] vs 48.5 [34.6-57.3], P = 0.0042; maximum amplitude [TEG-MA] = 22.7 [14.7-33.6] vs 32.2 [26.9-42.0], P < 0.0001). IWs were hyperfibrinolytic compared with control dogs on VCM whole-blood assays, with 25 U/mL tPA (lysis at 30 min [VCM-LI30] = 68.1 [0-100] vs\ 99.9 [63.3-100], P = 0.0009; lysis at 45 min [VCM-LI45] = 31.0 [0-100] vs 98.1 [38.4-100], P = 0.0002) but hypofibrinolytic compared with controls on TEG plasma assays with 50 U/mL tPA (lysis at 30 min [TEG-LY30] = 45.7 [4.6-94.6] vs 93.7 [12.3-96.5], P = 0.0004; lysis at 60 min [TEG-LY60] = 68.7 [29.7-96.8] vs 95.7 [34.4-97.6], P = 0.0003). Minimal fibrinolysis was measured on whole-blood VCM or plasma TEG assays without the addition of tPA, and there were no differences between the 2 groups. CONCLUSIONS: Weaker clots were found in IWs than control dogs. With the addition of tPA, IWs had evidence of hyperfibrinolysis on whole-blood VCM assays and hypofibrinolysis on plasma TEG assays compared with control dogs. Without the addition of tPA, however, both groups of dogs showed minimal fibrinolysis on viscoelastic testing.

Management of Anticoagulation and Antifibrinolytics in Catastrophic Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder that presents with hypercoagulability and results in a lab artifact of prolonged PTT. The most severe form is catastrophic antiphospholipid antibody syndrome (CAPS), which manifests as rapidly progressing thromboses in multiple organ systems leading to multi-organ ischemia. The mainstay management CAPS is anticoagulation and systemic corticosteroids. Antifibrinolytic agents have previously been thought to be relatively contraindicated in CAPS due to the pro-thrombotic nature of the disease; the complex coagulation profile of CAPS can make it difficult to assess the risks and benefits of antifibrinolytic therapy. Also, should a patient with CAPS require cardiopulmonary bypass (CPB) for surgery, it poses a unique challenge in providing appropriate anticoagulation in the setting of prolonged ACT. We present a case of a 32-year-old postpartum female with CAPS requiring heart transplant who safely received intraoperative antifibrinolytic therapy and was successfully anticoagulated during CPB after perioperative plasmapheresis.

Effect of the administration route on the hemostatic efficacy of tranexamic acid in patients undergoing short-segment posterior lumbar interbody fusion: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) is an FDA-approved antifibrinolytic that is seeing increased popularity in spine surgery owing to its ability to reduce intraoperative blood loss (IOBL) and allogeneic transfusion requirements. The present study aimed to summarize the current literature on these formulations in the context of short-segment instrumented lumbar fusion including ≥ 1-level posterior lumbar interbody fusion (PLIF). METHODS: The PubMed, Cochrane, and Web of Science databases were queried for all full-text English studies evaluating the use of topical TXA (tTXA), systemic TXA (sTXA), or combined tTXA+sTXA in patients undergoing PLIF. The primary endpoints of interest were operative time, IOBL, and total blood loss (TBL); secondary endpoints included venous thromboembolic complication occurrence, and allogeneic and autologous transfusion requirements. Outcomes were compared using random effects. Comparisons were made between the following treatment groups: sTXA, tTXA, and sTXA+tTXA. Given that sTXA is arguably the standard of care in the literature (i.e., the most common route of administration that to this point has been studied the most), the authors compared sTXA versus tTXA and sTXA versus sTXA+tTXA. Study heterogeneity was assessed with the I2 test, and grouped analysis using the Hedge's g test was performed for measurement of effect size. RESULTS: Forty-five articles were identified, of which 17 met the criteria for inclusion with an aggregate of 1008 patients. TXA regimens included sTXA only, tTXA only, and various combinations of sTXA and tTXA. There were no significant differences in operative time, TBL, or postoperative drainage between the sTXA and tTXA groups or between the sTXA and sTXA+tTXA groups. CONCLUSIONS: The present meta-analysis suggested clinical equipoise between isolated sTXA, isolated tTXA, and combinatorial tTXA+sTXA formulations as hemostatic adjuvants/neoadjuvants in short-segment fusion including ≥ 1-level PLIF. Given the theoretically lower venous thromboembolism risk associated with tTXA, additional investigations using large cohorts comparing these two formulations within the posterior fusion population are merited. Although TXA has been shown to be effective, there are insufficient data to support topical or systemic administration as superior within the open PLIF population.

Impact of time to start of tranexamic acid treatment on rebleed risk and outcome in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: The ULTRA-trial investigated effectiveness of ultra-early administration of tranexamic acid (TXA) in subarachnoid hemorrhage (SAH) and showed that TXA reduces the risk of rebleeding without concurrent improvement in clinical outcome. Previous trials in bleeding conditions, distinct from SAH, have shown that time to start of antifibrinolytic treatment influences outcome. This post-hoc analysis of the ULTRA-trial investigates whether the interval between hemorrhage and start of TXA impacts the effect of TXA on rebleeding and functional outcome following aneurysmal SAH. PATIENTS AND METHODS: A post-hoc comparative analysis was conducted between aneurysmal SAH patients of the ULTRA-trial, receiving TXA and usual care to those receiving usual care only. We assessed confounders, hazard ratio (HR) of rebleeding and odds ratio (OR) of good outcome (modified Rankin Scale 0-3) at 6 months, and investigated the impact of time between hemorrhage and start of TXA on the treatment effect, stratified into time categories (0-3, 3-6 and >6 h). RESULTS: Sixty-four of 394 patients (16.2%) in the TXA group experienced a rebleeding, compared to 83 of 413 patients (19.9%) with usual care only (HR 0.86, 95% confidence interval (CI): 0.62-1.19). Time to start of TXA modifies the effect of TXA on rebleeding rate (p < 0.001), with a clinically non-relevant reduction observed only when TXA was initiated after 6 h (absolute rate reduction 1.4%). Tranexamic acid treatment showed no effect on good outcome (OR 0.96, 95% CI: 0.72-1.27) with no evidence of effect modification on the time to start of TXA (p = 0.53). DISCUSSION AND CONCLUSIONS: This study suggests that the effect of TXA on rebleeding is modified by time to treatment, providing a protective, albeit clinically non-relevant, effect only when started after 6 h. No difference in functional outcome was seen. Routine TXA treatment in the aneurysmal SAH population, even within a specified time frame, is not recommended to improve functional outcome.

Efficacy and utility of antifibrinolytics in pediatric spine surgery: a systematic review and network meta-analysis.

Antifibrinolytics have gained increasing attention in minimizing blood loss and mitigating the risks associated with massive transfusions, including infection and coagulopathy in pediatric patients undergoing spine surgery. Nevertheless, the selection of optimal agent is still a matter of debate. We aim to review the utility of these agents and compare the efficacy of antifibrinolytics in pediatric and adolescent spine surgeries. A comprehensive search was performed in Scopus, Web of Science, and MEDLINE databases for relevant works. Studies providing quantitative data on predefined outcomes were included. Primary outcome was perioperative bleeding between the groups. Secondary outcomes included transfusion volume, rate of complications, and operation time. Twenty-eight studies were included in the meta-analysis incorporating 2553 patients. The use of Tranexamic acid (RoM: 0.71, 95%CI: [0.62-0.81], p < 0.001, I2 = 88%), Aprotinin (RoM: 0.54, 95%CI: [0.46-0.64], p < 0.001, I2 = 0%), and Epsilon-aminocaproic acid (RoM: 0.71, 95%CI: [0.62-0.81], p < 0.001, I2 = 60%) led to a 29%, 46%, and 29% reduction in perioperative blood loss, respectively. Network meta-analysis revealed higher probability of efficacy with Tranexamic acid compared to Epsilon-aminocaproic acid (P score: 0.924 vs. 0.571). The rate of complications was not statistically different between each two antifibrinolytic agent or antifibrinolytics compared to placebo or standard of care. Our network meta-analysis suggests a superior efficacy of all antifibrinolytics compared to standard of care/placebo in reducing blood loss and transfusion rate. Further adequately-powered randomized clinical trials are recommended to reach definite conclusion on comparative performance of these agents and to also provide robust objective assessments and standardized outcome data and safety profile on antifibrinolytics in pediatric and adolescent pediatric surgeries.

Tranexamic acid reduces perioperative blood loss and postoperative hemoglobin loss during total ankle arthroplasty: A systematic review and meta-analysis of clinical comparative studies.

IMPORTANCE: Peri-operative blood loss during joint replacement procedures is a modifiable risk factor that impacts wound complications, hospital stay and total costs. Tranexamic acid (TXA) is an anti-fibrinolytic that has been widely used in orthopedic surgery, but its efficacy in the setting of total ankle arthroplasty (TAA) has not been quantified to date. AIM: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of administering TXA in patients undergoing TAA. EVIDENCE REVIEW: The Medline, Embase and Cochrane library databases were systematically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five comparative studies examining blood loss following administration of TXA for patients undergoing TAA were included. The outcome measures of interest were blood loss, reduction in hemoglobin concentration, transfusion requirements, total complications and wound complications. FINDINGS: In total, 194 patients received TXA and 187 patients did not receive TXA while undergoing TAA. Based on the common-effects model for total blood loss for the TXA group versus control, the standardized mean difference (SMD) was -0.7832 (95% CI, -1.1544, -0.4120; P â€‹< â€‹0.0001), in favor of lower total blood loss for TXA. Based on the random-effects model for reduction in hemoglobin for the TXA group versus control, the SMD was -0.9548 (95% CI, -1.7850, -0.1246; P â€‹= â€‹0.0242) in favor of lower hemoglobin loss for TXA. Based on the random-effects model for total complications for the TXA group versus control, the risk ratio was 0.512 (95% CI, 0.1588, 1.6512; P â€‹= â€‹0.1876), in favor of lower total complications for TXA but this was not statistically significant. CONCLUSIONS: This current review demonstrated that administration of TXA led to a reduction in blood loss and hemoglobin loss without an increased risk of the development of venous thromboembolism in patients undergoing TAA. No difference was observed with respect to total complication rates between the TXA cohort and the control group. TXA appears to be an effective hemostatic agent in the setting of TAA, but further studies are necessary to identify the optimal timing, dosage and route of TXA during TAA. LEVEL OF EVIDENCE: III.

Procedural outcomes in children with mild type 1 von Willebrand disease.

Background: In patients with mild type 1 von Willebrand disease (VWD), treatment guidelines suggest individualization of surgical management. However, these conditional recommendations are based on very low-certainty evidence due to limited data on surgical outcomes in this population. Objectives: To characterize procedural bleeding prophylaxis strategies and outcomes in children with mild type 1 VWD. Methods: This is a retrospective cohort study that included patients aged between 0 and 21 years with mild type 1 VWD (defined as von Willebrand factor antigen and/or an activity of 30-50 IU/dL) who underwent a procedure from July 1, 2017, to July 1, 2022. Demographic, surgical, medication, and bleeding data were collected by manual chart review. Results: A total of 161 procedures were performed in 108 patients. The population was primarily female (75%), White (77.8%), and non-Hispanic (79.6%). Median age was 15.8 years (IQR, 8.2-17.6). Fifty-nine surgeries were classified as major, 66 as minor, and 36 as dental. For most procedures, patients received only antifibrinolytics for bleeding prophylaxis (n = 128, 79.5%); desmopressin was used in 17 (10.6%) procedures, and von Willebrand factor concentrate was used in 12 (7.5%) procedures. Bleeding complications occurred in 8 (5.0%) procedures: these included 1 major, 4 clinically relevant nonmajor, and 3 minor bleeding events. No patient required blood transfusion or an additional procedure to achieve hemostasis. Most bleeding complications were seen following intrauterine device (IUD) placement (5/8). Nearly 30% of patients who underwent IUD placement reported bleeding. Conclusion: Pediatric patients with mild type 1 VWD can safely undergo procedures using a tailored approach. Bleeding complications were uncommon, with the majority following IUD placement.

The Critical Blood-Sparing Effect of Tranexamic Acid (TXA) in Liposuction: A Systematic Review and Meta-Analysis.

Introduction: Tranexamic acid (TXA) has been used to improve bleeding outcomes in many surgical procedures. However, its blood-sparing effect in liposuction is not well established. Methods: A systematic literature search was performed using PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central, ClinicalTrials.gov, and WorldWideScience.org databases from their inception to October 8, 2021, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors focused on 3 main topics: 1) TXA, 2) liposuction, and 3) complications. We included articles evaluating the potential blood-sparing effects of TXA in liposuction. Studies were excluded if they were systematic review articles or protocol papers, animal studies, conference abstracts, survey studies, or non-English publications. Results: A total of 711 articles were identified, with 1 retrospective and 4 prospective (3 randomized) studies meeting our inclusion criteria. TXA was used in various forms: administered intravenously either on induction or after the procedure, mixed into the tumescent solution, or infiltrated into the liposuction sites after lipoaspiration. A significantly smaller reduction in hematocrit was noted in the TXA group compared with that in the non-TXA group (p<0.001) despite a significantly greater amount of lipoaspirate removed in the TXA group (p<0.001). Patients in non-TXA cohorts experienced adverse effects (such as seroma and need for transfusion) that were not seen in TXA cohorts. Conclusion: TXA use in patients undergoing liposuction seems to be associated with a beneficial blood-sparing effect, which may enhance safety in this population. Future studies should aim to determine the optimal route and dosing for TXA in liposuction. Evidence Based Medicine: Level IV.

In Nordic countries 30-day mortality rate is half that estimated with EuroSCORE II in high-risk adult patients given aprotinin and undergoing mainly complex cardiac procedures.

Objectives. To describe current on- (isolated coronary arterty bypass grafting, iCABG) and off-label (non-iCABG) use of aprotinin and associated safety endpoints in adult patients undergoing high-risk cardiac surgery in Nordic countries. Design. Data come from 10 cardiac surgery centres in Finland, Norway and Sweden participating in the European Nordic aprotinin patient registry (NAPaR). Results. 486 patients were given aprotinin between 2016 and 2020. 59 patients (12.1%) underwent iCABG and 427 (87.9%) non-iCABG, including surgery for aortic dissection (16.7%) and endocarditis (36.0%). 89.9% were administered a full aprotinin dosage and 37.0% were re-sternotomies. Dual antiplatelet treatment affected 72.9% of iCABG and 7.0% of non-iCABG patients. 0.6% of patients had anaphylactic reactions associated with aprotinin. 6.4% (95 CI% 4.2%-8.6%) of patients were reoperated for bleeding. Rate of postoperative thromboembolic events, day 1 rise in creatinine >44µmol/L and new dialysis for any reason was 4.7% (95%CI 2.8%-6.6%), 16.7% (95%CI 13.4%-20.0%) and 14.0% (95%CI 10.9%-17.1%), respectively. In-hospital mortality and 30-day mortality was 4.9% (95%CI 2.8%-6.9%) and 6.3% (95%CI 3.7%-7.8%) in all patients versus mean EuroSCORE II 11.4% (95%CI 8.4%-14.0%, p < .01). 30-day mortality in patients undergoing surgery for aortic dissection and endocarditis was 6.2% (95%CI 0.9%-11.4%) and 6.3% (95%CI 2.7%-9.9%) versus mean EuroSCORE II 13.2% (95%CI 6.1%-21.0%, p = .11) and 14.5% (95%CI 12.1%-16.8%, p = .01), respectively. Conclusions. NAPaR data from Nordic countries suggest a favourable safety profile of aprotinin in adult cardiac surgery.

Use of crushed tranexamic acid tablets in water for paediatric patients with bleeding disorders.

BACKGROUND: Ε-Aminocaproic acid oral solution (EACA OS) is the only commercially available antifibrinolytic for patients who cannot swallow tablets. Insurance denials and high costs remain barriers to its use. OBJECTIVES: To determine the safety and efficacy of crushed tranexamic acid tablets in water (cTXAw) for children with bleeding disorders. METHODS: We retrospectively reviewed records of children (<10 years) with bleeding disorders who received cTXAw or EACA OS from 1 December 2018, through 31 July 2022, at Mayo Clinic (Rochester, Minnesota). Bleeding outcomes were defined according to ISTH criteria. RESULTS: Thirty-two patients were included (median age, 3 years; male, n = 23). Diagnoses were VWD (n = 17), haemophilia (n = 5), FVII deficiency (n = 3), inherited platelet disorder (n = 4), ITP (n = 2), and combined FV and FVII deficiencies (n = 1). Thirty-two courses of cTXAw (monotherapy 24/32; mean duration 6 days) and fifteen courses of EACA (monotherapy 12/15; mean duration 5 days) were administered. No surgical procedures (n = 28) were complicated by bleeding. Of the 19 bleeding events, 16 had effective haemostasis, two had no reported outcome, and one had no response. cTXAw and EACA were equally effective in preventing and treating bleeding (p value > .1). No patients had adverse effects. Eight of 19 patients (42%) who were initially prescribed EACA OS did not receive it because of cost or insurance denial. The estimated average wholesale price of one treatment was $94 for cTXAw and $905 for EACA OS. CONCLUSIONS: CTXAw appears to be an effective, safe, and low-cost alternative option to EACA OS for young children with bleeding disorders.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Antifibrinolytics.

The use of strategies to reduce blood loss and transfusions is essential in the treatment of surgical patients, including in complex cardiac surgeries and those that use cardiopulmonary bypass. Antifibrinolytics, such as epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), are widely used in these procedures, as well as in other types of surgeries. These medicines are included in the World Health Organization (WHO) list of 'essential medicines'. Scientific evidence demonstrates the effectiveness of EACA in reducing bleeding and the need for transfusions in heart surgery. EACA is highly recommended for use in heart surgery by the American Society of Anesthesiology Task Force on Perioperative Blood Management. Regarding the safety of EACA, there is no robust evidence of any significant thrombotic potential. TXA has also been shown to be effective in reducing the use of blood transfusions in cardiac and non-cardiac surgeries and is considered safer than other antifibrinolytic agents. There is no evidence of any increased risk of thromboembolic events with TXA, but doses greater than 2 g per day have been associated with an increased risk of seizures. It is also important to adjust the dose in patients with renal impairment. In conclusion, antifibrinolytics, such as EACA and TXA, are effective in reducing blood loss and transfusion use in cardiac and non-cardiac surgeries, without causing serious adverse effects.

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.

Tranexamic acid in patients with traumatic brain injury: a meta-analysis.

BACKGROUND: We performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). METHODS: We searched the literature for articles evaluating the effectiveness and safety of tranexamic acid (TXA) in TBI published between January 2012 and January 2021, and identified 8 studies with a total of 10860 patients: 5660 received TXA and 5200 served as controls. We used a dichotomous or continuous approach with a random or fixed-effect model to assess the efficacy and safety of TXA in TBI, and calculated the mean difference (MD) and odds ratio (OR) with the corresponding 95% confidence interval. RESULTS: In patients with TBI, early administration of TXA was associated with a greater relative benefit (MD -2.45; 95% CI = -4.78 to -0.12; p=0.04) and less total haematoma expansion (MD - 2.52; 95% CI = -4.85 to -0.19; p=0.03) compared to controls. There were no statistically significant differences in mortality (OR 0.94; 95% CI=0.85-1.03; p=0.18), presence of progressive haemorrhage (OR 0.75; 95% CI=0.56-1.01; p=0.06), need for neurosurgery (OR 1.15; 95% CI=0.66-1.98; p=0.63), high Disability Rating Scale score (OR 0.90; 95% CI=0.56-1.45; p=0.68), and incidence of ischaemic or thromboembolic complications (OR 1.34; 95% CI=0.33-5.46; p=0.68) between TBI patients treated with TXA and controls. CONCLUSIONS: Early administration of TXA in TBI patients may have a greater relative benefit and may inhibit haematoma expansion. There were no significant differences in mortality, presence of progressive haemorrhage, need for neurosurgery, high Disability Rating Scale score, and incidence of ischaemic or thromboembolic complications between TBI patients treated with TXA and controls. Further studies are needed to validate these results.