Antifibrinolytic and Adjunct Hemostatic Agents: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs). DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. MEASUREMENTS AND MAIN RESULTS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented. CONCLUSIONS: Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.

Intraarticular TXA Administration with Appropriate Timing of Clamping and Appropriate Dose is More Effective Than IV Administration.

PURPOSE OF THE STUDY: Our aim was to compare the effects of intraarticular and intravenous (IV) tranexemic acid (TXA) application on bleeding and complication rates in patients who underwent total knee arthroplasty (TKA). MATERIAL AND METHODS: Between 2017 and 2021, 406 patients who underwent TKA with 2 g of IV TXA and retrograde 1.5 g of TXA applied through the drain were included in the study. Of the patients, 206 were in the IV TXA group. Preoperative and postoperative hemoglobin levels, drain output, BMI, ASA score, blood loss, and the number of transfused patients were recorded. Complications such as symptomatic venous thromboembolism were also recorded. RESULTS: There was no significant difference between the two groups in terms of age, sex, American Society of Anesthesiologists (ASA) score, or BMI (p = 0.68, 0.54, 0.28, 0.45). Total drain output and blood loss were significantly higher in the IV TXA group than in the intraarticular TXA group (p < 0.0001, p < 0.0001). Eighteen patients in the IV TXA group and 1 patient in the intraarticular TXA group received a blood transfusion (p < 0.0001). There was no difference between the two groups in terms of preoperative hemoglobin or platelet count (p = 0.24). However, postoperative hemoglobin level was higher in the patients who received intraarticular TXA (p=0.0005). More thromboembolism events were seen in the IV TXA group (p < 0.0001). CONCLUSIONS: Intraarticular TXA application reduces blood loss more than IV application, reduces the blood transfusion rate, and causes fewer complications. KEY WORDS: tranexemic acid, total knee arthroplasty, intraarticular injection, blood loss, blood transfusion.

Clinical application of tranexamic acid in arthroscopic rotator cuff repair surgery: A randomized controlled trial.

BACKGROUND: To investigate whether intravenous administration of tranexamic acid (TXA) prior to arthroscopic rotator cuff repair improves operative blood loss, postoperative fibrinolytic index, inflammatory response, and postoperative pain. METHODS: This was a prospective, double-blind, randomized controlled study. From January 2023 to February 2024, 64 patients who required arthroscopic rotator cuff repair were included and divided into tranexamic acid group (T group) group and control group (C group) according to the random number table method. In T group, 1000 mg TXA was administered intravenously 10 minutes before surgery, and an equivalent dose of normal saline was administered intravenously 10 minutes before surgery in C group. Intraoperative bleeding, postoperative fibrinolytic indexes, inflammatory indexes, pain scores, and occurrence of adverse effects were compared between the 2 groups. RESULTS: Intraoperative bleeding in T group was lower than that in C group (P < .05); D-D and FDP in T group were significantly lower than those in C group (P < .05); postoperative TNF-α and IL-6 in 2 groups was higher than that before operation and T group was lower than C group (P < .05); The pain scores of the 2 groups after operation were lower than those before operation (P < .05), and there was no difference between the 2 groups (P > .05). CONCLUSION SUBSECTIONS: TXA is able to reduce blood loss and inflammatory reactions, modulate fibrinolytic function, and promote postoperative recovery in patients undergoing arthroscopic rotator cuff repair, with no elevated risk of complications.

Clinical Efficacy of Intra-articular Tranexamic Acid Injection in the Management of Hemophilia with Total Hip Arthroplasty: A 24-month Retrospective Cohort Study.

OBJECTIVE: Total hip arthroplasty (THA) effectively treats end-stage hemophilic hip arthropathy. Given hemophilia's unique characteristics, perioperative bleeding remains a significant risk for patients undergoing THA. Tranexamic acid (TXA), an efficient antifibrinolytic agent, may benefit the outcomes of THA for patients with hemophilia (PWH). This study aims to explore the clinical efficacy of intra-articular injection of TXA in treating perioperative bleeding in PWH and assess its additional clinical benefits. METHODS: The retrospective study comprised data of PWH who received THA from January 2015 to December 2021 in the research center. A total of 59 individuals were included in the study, divided into a TXA group (n = 31) and a non-TXA group (n = 28). We compared various parameters, including total blood loss (TBL), visible blood loss (VBL), occult blood loss (OBL), intraoperative coagulation factor VIII (FVIII) consumption, perioperative total FVIII consumption, hemoglobin (HB), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), length of hospital stay, hospitalization costs, length of surgery, total protein, activated partial thromboplastin time (APTT), D-dimer, rate of joint swelling, hip joint range of motion (ROM), visual analogue scale (VAS), and Harris hip joint function scale (HHS) between the two groups. Follow-up assessments were conducted for up to 24 months. A Student's t test was utilized for the statistical analysis. RESULTS: This study demonstrated that intra-articular TXA effectively reduced TBL (1248.19 ± 439.88 mL, p < 0.001), VBL (490.32 ± 344.34 mL, p = 0.003), and OBL (757.87 ± 381.48 mL, p = 0.004) in PWH who underwent THA. TXA demonstrated effectiveness in reducing VAS scores on POD1, POD7, and POD14 and joint swelling rates on POD1, POD7, POD14, and at discharge (p < 0.05). Additionally, the TXA group achieved higher HHS ratings at all follow-up time points (p < 0.05), showing superior hip joint mobility, lower postoperative inflammation levels, reduced factor VIII consumption during surgery, and less postoperative nutritional loss. No statistically significant differences were observed between the two groups in terms of hospital stay, hospitalization costs, surgery duration, and coagulation indicators. CONCLUSION: Intra-articular injection of TXA reduces perioperative bleeding in PWH undergoing THA while also improving joint mobility, post-operative rehabilitation, and quality of life. This may provide value for the future application of TXA in PWH.

Tranexamic acid as a therapeutic option for melasma management: meta-analysis and systematic review of randomized controlled trials.

Purpose: This study aimed to evaluate the efficacy of tranexamic acid (TXA) in treating melasma through a meta-analysis and systematic review of randomized controlled trials (RCTs). The study focused on identifying associated adverse effects and comparing TXA's effectiveness with other melasma treatments.Materials and methods: Following PROSPERO and PRISMA guidelines, an extensive electronic search was conducted across four databases for RCTs on TXA use in melasma. Inclusion criteria encompassed full-text English articles with specific outcome measures, while studies with high bias risk or non-English publications were excluded. Data were extracted from 22 relevant studies and analyzed using the RevMan software, with heterogeneity identified using I² statistics and forest plots.Results: A total of 22 studies with 1280 patients were included. TXA was administered orally, topically, or via injection, with treatment durations ranging from 8 weeks to nearly 2 years. TXA significantly reduced melasma severity, evidenced by reductions in MASI, mMASI, MI, and hemi-MASI scores. Oral TXA showed the most substantial decrease in MASI scores, followed by injections and topical applications. However, studies exhibited high heterogeneity, particularly in combined treatments. Adverse effects included gastrointestinal discomfort, skin irritation, and menstrual irregularities.Conclusions: TXA is effective in treating melasma, either alone or combined with other treatments. Despite significant reductions in melasma severity, further research is necessary to standardize TXA administration methods and address long-term effects. The high heterogeneity observed suggests a need for more consistent treatment protocols.

Perioperative Administration of Tranexamic Acid and Low Molecular Weight Heparin for Enhanced Blood Management in Intertrochanteric Fractures: A Randomized Controlled Study.

BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated with intramedullary nailing (IMN) using 3 regimens of combined tranexamic acid (TXA) and low molecular weight heparin (LMWH), proposing a novel therapy of 4-dose TXA. MATERIAL AND METHODS We recruited 79 patients and randomly divided them into 3 groups. The 4-dose TXA group (22 patients) received 1.0 g intravenous TXA 30 min before surgery and 1.0 g at intervals of 3, 6, and 9 h before surgery. The 1-dose TXA group (25 patients) received 1.0 g intravenous TXA 30 min before surgery, while the control group (32 patients) did not receive TXA. LMWH was applied 12 h after surgery in each group. The primary metrics evaluated included hidden blood loss (HBL), total blood loss (TBL), and the number and incidence rate of deep vein thrombosis (DVT). RESULTS Analysis of the HBL revealed that the 4-dose TXA group had the lowest average (583.13±318.08 ml), followed by the 1-dose TXA group (902.94±509.99 ml), and the control group showed the highest (1154.39±452.06 ml) (P<0.05). A similar result was observed for TBL (4-dose group: 640.86±337.22 ml, 1-dose group: 971.74±511.14 ml, control group: 1226.27±458.22 ml, P<0.05). Regarding DVT, the 4-dose TXA group had 5 cases (incidence rate 22.73%), the 1-dose TXA group had 6 cases (incidence rate 24.00%), and the control group had 8 cases (incidence rate 25.00%), with no significant difference among groups (P>0.05). CONCLUSIONS Treatment using 4-dose TXA and LMWH can effectively reduce PBL without increasing the DVT risk in IF patients with IMN.

Hospital policy of tranexamic acid to reduce transfusion in major non-cardiac surgery (TRACTION): protocol for a phase IV randomised controlled trial.

INTRODUCTION: Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic surgeries. While the use of TXA in these surgeries is routine, its efficacy and safety in other surgeries, including oncologic surgeries, with comparable rates of transfusion are uncertain. Our primary objective is to evaluate whether a hospital-level policy implementation of routine TXA use in patients undergoing major non-cardiac surgery reduces RBC transfusion without increasing thrombotic risk. METHODS AND ANALYSIS: A pragmatic, registry-based, blinded, cluster-crossover randomised controlled trial at 10 Canadian sites, enrolling patients undergoing non-cardiac surgeries at high risk for RBC transfusion. Sites are randomised in 4-week intervals to a hospital policy of intraoperative TXA or matching placebo. TXA is administered as 1 g at skin incision, followed by an additional 1 g prior to skin closure. Coprimary outcomes are (1) effectiveness, evaluated as the proportion of patients transfused RBCs during hospital admission and (2) safety, evaluated as the proportion of patients diagnosed with venous thromboembolism within 90 days. Secondary outcomes include: (1) transfusion: number of RBC units transfused (both at a hospital and patient level); (2) safety: in-hospital diagnoses of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism; (3) clinical: hospital length of stay, intensive care unit admission, hospital survival, 90-day survival and the number of days alive and out of hospital to day 30; and (4) compliance: the proportion of enrolled patients who receive a minimum of one dose of the study intervention. ETHICS AND DISSEMINATION: Institutional research ethics board approval has been obtained at all sites. At the completion of the trial, a plain language summary of the results will be posted on the trial website and distributed in the lay press. Our trial results will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT04803747.

The hemostatic and anti-inflammatory effects of intravenous single-dose of tranexamic acid in double-segment posterior lumbar interbody fusion: a case control study.

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.

Efficacy and Safety of Oral Tranexamic Acid vs. Other Routes in Total Joint Arthroplasty: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Total joint arthroplasty (TJA) is often associated with significant blood loss, leading to complications such as acute anemia and increased risk of infection and mortality. Tranexamic acid (TXA), an antifibrinolytic agent, has been recognized for effectively reducing blood loss during TJA. This systematic review and network meta-analysis aims to evaluate the efficacy and safety of oral TXA compared with other administration routes in TJA. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, Embase, and Web of Science, focusing on randomized clinical trials involving oral TXA in TJA. The studies were assessed for quality using the Cochrane risk assessment scale. Data synthesis involved network meta-analyses, comparing outcomes including hemoglobin drop, estimated blood loss (EBL), transfusion rate, and deep vein thrombosis (DVT) rate. RESULTS: Our comprehensive literature search incorporated 39 studies with 7,538 participants, focusing on 8 TXA administration methods in TJA. The combination of oral and intra-articular (oral + IA) TXA markedly reduced hemoglobin drop more effectively than oral, intravenous (IV), and IA alone, but the difference was not significant. Oral + IA TXA significantly reduced EBL more effectively than oral + IV, IA + IV, and oral, IV, and IA alone. Perioperative transfusion rates with oral + IA TXA was significantly lower than that of oral, IA, and IV alone. The DVT rate with oral + IA was significantly lower than that with all other routes, including oral + IV, IA + IV, and oral, IA, and IV alone. CONCLUSION: Oral TXA, particularly in combination with IA administration, demonstrates significantly higher efficacy in reducing blood loss and transfusion rates in TJA, with a safety profile comparable with that of other administration routes. The oral route, offering lower costs and simpler administration, emerges as a viable and preferable option in TJA procedures. LEVEL OF EVIDENCE: Level I. See Instructions for Authors for a complete description of levels of evidence.

Tranexamic Acid in Total Shoulder Arthroplasty: A Scoping Review of Current Practices and Future Directions.

BACKGROUND: The effectiveness of tranexamic acid (TXA) as an antifibrinolytic agent in total shoulder arthroplasty (TSA) is well documented; however, there remains considerable practice variability concerning the optimal route of administration and dosing protocols concerning the medication's use. Our aim was to conduct a scoping review of the literature regarding the efficacy of various methods of TXA administration in TSA and to identify knowledge gaps that may be addressed. METHODS: A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. The PubMed and MEDLINE electronic databases were searched to identify all articles published before March 2023 investigating the administration of TXA in TSA. Randomized controlled trials and cohort studies were included, and data were extracted to capture information regarding intervention details and related outcomes such as blood loss, transfusion needs, and complication rates. RESULTS: A total of 15 studies were included in this review. All selected studies used either intravenous (IV) or topical TXA, with 1 study also including a combined approach of both topical and IV TXA. Of the studies that used an IV approach, the most commonly reported favorable outcomes were a reduction in blood volume loss, reduction in hemoglobin or hematocrit change, and decreased drain output. Dosing varied significantly between all identified studies because some used a standard dosing amount in grams or milligrams for all treatment group participants, whereas others used weight-based dosing amounts. All studies that used a weight-based dosing regimen as well as studies using a standard dosing amount between 1,000 and 5,000 mg reported favorable outcomes for postoperative blood loss. CONCLUSION: Both IV and topical TXA clearly demonstrate favorable perioperative hematologic profiles in TSA. Although both approaches have demonstrated a successful association with decreased blood loss and transfusion requirements, there is no definitive benefit to choosing one over the other. Furthermore, the use of oral TXA either in combination or isolation warrants further study in TSA because of its comparable efficacy profiles and significantly lower associated costs of application.

Topical Tranexamic Acid to Control Vaginal Laceration Bleeding after Sexual Assault.

BACKGROUND: Sexual assault survivors may sustain vaginal trauma that requires intervention in the emergency department, or operating room. CASE REPORT: We describe the case of a 16-year-old female who was referred to the emergency department for evaluation of continued bleeding from a vaginal laceration following sexual assault 38 h prior. The bleeding limited the medical forensic medical examination, but she was hemodynamically stable. After the application of tranexamic acid (TXA)-soaked gauze, the patient's bleeding was controlled and the wound was able to be evaluated and the examination completed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first case in the literature that describes the use of topical TXA in a patient to achieve hemostasis in a vaginal laceration sustained from sexual violence.

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.

Total blood loss and early clinical outcomes under different tranexamic acid regimes in total knee arthroplasty.

BACKGROUND: Many different regimes of intravenous and local tranexamic acid (TXA) reduce total blood loss (TBL) in patients undergoing total knee arthroplasty (TKA). However, the most effective TXA regime in reducing blood loss might not be most beneficial for the patient. The aim of the present study was to investigate the effect of commonly used TXA regimes on blood loss and on early clinical outcomes. METHODS: We performed this monocentric retrospective study in patients undergoing primary TKA. Primary outcome was the estimated TBL. Secondary outcomes were the rates of adverse events (AE) as well as the range of motion (ROM), mobility and pain intensity during the first three physiotherapy sessions (PTS). RESULTS: We analysed the data of 1250 TKAs. 5 different TXA regimes were applied. TBL (mean ± SE) was 953 ± 64 ml (2xiv), 999 ± 19 ml (2xiv + 1xlocal), 1075 ± 19 ml (1xiv + 1xlocal), 1191 ± 39 ml (1xlocal) and 1241 ± 48 ml (1xiv) (p < 0.01). In the linear regression model for TBL a lower number of TXA applications was a predictor for increased blood loss (p < 0.01). AE rates were lowest under 2xiv (0%) and 2xiv + 1xlocal (4.8%). Highest mobility and lowest pain intensity were observed under 1x iv and 2x iv. The largest portions of fully mobile patients on day three were observed under 1xiv (100%), 2xiv (100%) and 2xiv + 1local TXA (86.9%). CONCLUSION: Our results suggest that multiple applications of TXA are more effective in decreasing blood loss than excessive dosing of TXA. Interestingly, local use of TXA might be associated with higher pain intensity and decreased mobility on the first days after surgery.