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.

Efficacy and safety of topical application of tranexamic acid in patients undergoing reconstructive plastic surgery after excision of facial skin cancers: a randomised clinical trial.

INTRODUCTION: Tranexamic acid (TA) has attracted increased attention among surgical specialties, but its use in plastic surgery is limited. The aim of this study was to assess the efficacy and safety of topical administration of 3% TA solution in reconstructive surgery of the face and scalp after excision of skin cancers. METHODS: a randomized, double-blind, parallel-group clinical trial was conducted in patients aged 18 years or older with malignant skin neoplasms in the face or scalp region (ICD-10 C44.9). The primary outcome was volume of blood loss in the intraoperative and immediate postoperative period. Secondary outcomes included difficult-to-control intraoperative haemorrhage, hematoma, ecchymosis, and other adverse events. RESULTS: of the 54 included patients, 26 were randomised to TA group and 28 to placebo group. The mean blood loss was 11.42ml (SD 6.40, range 8.83-14.01) in the TA group, and 17.6ml (SD 6.22, range 15.19-20.01) in the placebo group, representing a mean decrease of 6.18ml (35.11%) (p=0.001). TA significantly reduced the risk of ecchymosis (RR = 0.046; 95% CI: 0.007-0.323). Only two patients in the placebo group experienced ischemia in the flaps, and one patient in the placebo group experienced tissue necrosis requiring surgical reintervention. There were no surgical wound infections, thromboembolic phenomena, or other adverse events related to TA. CONCLUSIONS: topical TA may reduce intraoperative and immediate postoperative bleeding, with a significantly decreased risk of ecchymosis. There is no evidence of ischemic damage of flaps, systemic thromboembolic complications, or other adverse events.

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.

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.

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.

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.

Evaluation of the prehospital administration of tranexamic acid for injured patients: a state-wide observational study with sex and age-disaggregated analysis.

BACKGROUND: Tranexamic acid (TXA) decreases mortality in injured patients and should be administered as soon as possible. Despite international guidelines recommending TXA in the prehospital setting, its use remains low. The aim of this study was to assess the prehospital administration of TXA for injured patients in a Swiss region. METHODS: We conducted a retrospective observational study in Switzerland between 2018 and 2021. Inclusion criteria were injured patients ≥18 years for whom an ambulance or helicopter was dispatched. The exclusion criterion was minor injury defined by a National Advisory Committee for Aeronautics score <3. The primary outcome was the proportion of patients treated with TXA according to guidelines. The European guidelines were represented by the risk of death from bleeding (calculated retrospectively using the Bleeding Audit for Trauma and Triage (BATT) score). Factors impacting the likelihood of receiving TXA were assessed by multivariate analysis. RESULTS: Of 13 944 patients included in the study, 2401 (17.2%) were considered at risk of death from bleeding. Among these, 257 (11%) received prehospital TXA. This represented 38% of those meeting US guidelines. For European guidelines, the treatment rate increased with the risk of death from bleeding: 6% (95% CI 4.4% to 7.0%) for low risk (BATT score 3-4); 13% (95% CI 11.1% to 15.9%) for intermediate risk (BATT score 5-7); and 21% (95% CI 17.6% to 25.6%) for high risk (BATT score ≥8) (p<0.01). Women and the elderly were treated less often than men and younger patients, irrespective of the risk of death from bleeding and the mechanism of injury. CONCLUSION: The proportion of injured patients receiving TXA in the prehospital setting of the State of Vaud in Switzerland was low, with even lower rates for women and older patients. The reasons for this undertreatment are probably multifactorial and would require specific studies to clarify and correct them.

The effectiveness and safety of 3% tranexamic acid cream vs. 4% hydroquinone cream for mixed-type melasma in skin of color: a double-blind, split-face, randomized controlled trial.

INTRODUCTION: Melasma, a chronic acquired skin pigmentation disorder, is characterized by the presence of irregular-edged brown to gray-brown patches with a symmetrical distribution, primarily on sun-exposed areas such as the face. Topical hydroquinone (HQ) is the gold standard for melasma treatment but has numerous side effects. This study assesses the effectiveness of topical tranexamic acid (TA) as an alternative for melasma treatment. METHODS: In a double-blind, split-face, randomized controlled trial involving 20 subjects, the effectiveness of 3% TA versus 4% HQ cream was evaluated over 8 weeks. The modified melasma area and severity index (mMASI), melanin index, erythema index, and side effects were assessed. Subjective improvement was measured using the patient global assessment (PtGA). RESULTS: A significant decline in the mMASI score was observed at weeks 4 and 8 in both groups compared to baseline. There were no statistically significant differences in PtGA scores between the 3% TA group and the 4% HQ group. CONCLUSIONS: Topical 3% TA is as effective and safe as 4% HQ for treating melasma in the Indonesian population, with potential advantages in terms of side-effect profiles.

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.

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.

Improved outcome with individualised antifibrinolytic therapy: what is the evidence?

Viscoelastic haemostatic testing (VHT) has been used to determine hyperfibrinolysis and hypofibrinolysis. When modified by addition of tissue plasminogen activator (tPA), VHT has been suggested to assess responses to antifibrinolytic therapy and to estimate the concentration of tranexamic acid in patients undergoing cardiac surgery. Despite some evidence that tPA-modified VHT might allow individualisation of antifibrinolytic therapy, further studies are warranted to prove its clinical benefit for postsurgical bleeding, transfusion of blood products, and thromboembolic events.

Effect of tranexamic acid on postoperative blood loss.

The aim of this article was to evaluate the efficacy of tranexamic acid (TXA) to reduce blood loss after maxillofacial fracture surgery. Clinical data were collected retrospectively on patients with unilateral fractures of the zygomaticomaxillary complex (ZMC) or mandibular condyle. Patients were then further divided into TXA and control groups according to whether or not TXA was used after surgery. The amount of postoperative blood loss was evaluated by negative pressure drainage volume. Data were statistically analysed. In patients with unilateral ZMC fractures, total postoperative blood loss in the TXA group was about 30 ml less than that in the control group (p = 0.006). It was significantly less on the first and second postoperative days. However, in patients with unilateral mandibular condylar fractures, there was no significant difference between the TXA and control groups (p = 0.917). TXA can reduce postoperative bleeding in patients with ZMC fractures, and the optimal usage time is on the first and second postoperative days. For patients with mandibular condylar fractures, TXA may not be used.

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.

Strategies for optimising early detection and obstetric first response management of postpartum haemorrhage at caesarean birth: a modified Delphi-based international expert consensus.

OBJECTIVE: There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert's consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth. DESIGN: Systematic review and three-stage modified Delphi expert consensus. SETTING: International. POPULATION: Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance. OUTCOME MEASURES: Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth. RESULTS: Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman's haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman's haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach. CONCLUSION: These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step.