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OBJECTIVE Tranexamic acid (TXA) is an antifibrinolytic agent associated with reduced blood loss and mortality in a wide range of procedures, including spine surgery, traumatic brain injury, and craniosynostosis. Despite this wide use, the safety and efficacy of TXA in spine surgery has been considered controversial due to a relative scarcity of literature and lack of statistical power in reported studies. However, if TXA can be shown to reduce blood loss in laminectomy with fusion and posterior instrumentation, more surgeons may include it in their armamentarium. The authors aimed to conduct an up-to-date systematic review and meta-analysis of the efficacy of TXA in reducing blood loss in laminectomy and fusion with posterior instrumentation. METHODS A systematic review and meta-analysis, abiding by PRISMA guidelines, was performed by searching the databases of PubMed, Web of Science, and Cochrane. These platforms were queried for all studies reporting the use of TXA in laminectomy and fusion with posterior instrumentation. Variables retrieved included patient demographics, surgical indications, involved spinal levels, type of laminectomy performed, TXA administration dose, TXA route of administration, operative duration, blood loss, blood transfusion rate, postoperative hemoglobin level, and perioperative complications. Heterogeneity across studies was evaluated using a chi-square test, Cochran’s Q test, and I2 test performed with R statistical programming software. RESULTS A total of 7 articles were included in the qualitative study, while 6 articles featuring 411 patients underwent statistical analysis. The most common route of administration for TXA was intravenous with 15 mg/kg administered preoperatively. After the beginning of surgery, TXA administration patterns were varied among studies. Blood transfusions were increased in non-TXA cohorts compared to TXA cohorts. Patients administered TXA demonstrated a significant reduction in blood loss (mean difference −218.44 mL; 95% CI −379.34 to −57.53; p = 0.018). TXA administration was not associated with statistically significant reductions in operative durations. There were no adverse events reported in either the TXA or non-TXA patient cohorts. CONCLUSIONS TXA can significantly reduce perioperative blood loss in cervical, thoracic, and lumbar laminectomy and fusion procedures, while demonstrating a minimal complication profile.

Several drugs that reduce functional levels of the plasma protease zymogen factor XI (FXI), or that inhibit its activated form (FXIa), are being evaluated as treatments to prevent thrombosis. Based on the observation that individuals with inherited FXI deficiency have a relatively mild bleeding disorder, it is anticipated that therapeutic FXI(a) inhibitors will have a smaller impact on hemostasis than anticoagulants targeting thrombin or factor Xa. However, even if FXI(a) inhibitors are determined to be safer than currently used anticoagulants, some patients on these drugs will experience abnormal bleeding or require emergent surgery. Strategies for dealing with such situations are required. Treatment with antifibrinolytic agents and low doses of recombinant factor VIIa effectively prevent abnormal bleeding in FXI-deficient patients with alloantibody inhibitors to FXI who undergo surgery. We propose that a similar strategy can be used for patients on therapeutic FXI(a) inhibitors who are bleeding or require invasive procedures.

Background and Aim Multilevel posterior spinal fusion surgery in adults is associated with significant intra- and postoperative blood loss. Tranexamic acid (TXA) is an antifibrinolytic agent for reducing blood loss and allogenic blood transfusion. The purpose of this study was to evaluate the efficiency of TXA in reducing blood loss and improving hematologic parameters in adult patients undergoing posterior thoracic/lumbar instrumented spinal fusion surgery. Patients and Methods This is a retrospective observational study comparing the intra- and postoperative hemodynamic findings of two groups treated with and without TXA. The study included 112 adult patients receiving elective posterior thoracic/lumbar instrumented spinal fusion surgery. The patients were evaluated in terms of age, gender, type of surgery, intraoperative blood loss, pre- and postoperative hemoglobin (Hb) and hematocrit values, postoperative systemic anticoagulant use, intra- and postoperative use of blood products, and the volume of the drainage fluid as an indicator of postoperative blood loss. The TXA group received preoperative 10 mg/kg intravenous TXA, another dose of 10 mg/kg/h in isotonic solution during the operation, and local administration of TXA before the closure of the surgical site (1g in patients undergoing surgery in ≤3 segments, and 2g in patients undergoing surgery in ≥4 segment group). Results Intra- and postoperative blood loss and need for transfusion were significantly lower in the TXA group. Fifty-three of 112 patients required intra- and postoperative transfusion, and postoperative anticoagulants were given to 25/112 patients. The postoperative Hb level was lower, and the difference of pre- and postoperative Hb values was higher in the non-TXA group (not significant). Conclusion Simultaneous systemic and topical application of TXA is a safe and efficient blood conservation strategy for adult patients undergoing major multilevel spinal surgery.

Children and adolescents undergoing posterior spinal fusion for scoliosis experience high rates of bleeding and blood product transfusion. Antifibrinolytic therapy is one key strategy to decrease blood loss and transfusion in pediatric scoliosis surgery. Here we review 172 pediatric scoliosis patients (birth to 21 y) who underwent posterior spinal fusion at our institution from 2017 to 2018. We reported rates of blood loss and transfusion, compared patients receiving tranexamic acid to a e-aminocaproic acid, and evaluated antifibrinolytic agent and laboratory parameters as predictors of blood loss and transfusion. Intraoperatively, 62% received tranexamic acid and 38% received e-aminocaproic acid. Overall, blood loss (mean intraoperative estimated blood loss=14.9±9.7 mL/kg, 22% with clinically significant blood loss [>20 mL/kg], and mean calculated hemoglobin mass loss=175.9±70.1 g) and transfusion rates (15% with intraoperative allogeneic red blood cell transfusion and mean intraoperative allogeneic red blood cell transfusion volume=12.5±7.1 mL/kg) were similar to previous cohorts studying intraoperative antifibrinolytics. There was no difference in intraoperative estimated blood loss, clinically significant blood loss, calculated hemoglobin mass loss, or transfusion rates between the antifibrinolytic groups. Antifibrinolytic choice was not predictive of blood loss or transfusion. Routine hematologic laboratory parameters and antifibrinolytic choice were insufficient to predict blood loss or other outcomes. Future prospective laboratory-based studies may provide a more comprehensive model of surgical-induced coagulopathy in scoliosis surgery and provide a better tool for predicting blood loss and improving outcomes.

Blood loss is a potential cause of morbidity and mortality in craniosynostosis surgery. Recent reports have suggested that the use of tranexamic acid (TXA), an antifibrinolytic agent, mitigates this blood loss. A retrospective cohort study of patients undergoing craniosynostosis surgery at a tertiary craniofacial hospital in Sydney was undertaken. Primary outcomes were blood loss and transfusion requirements. Two groups were compared: those who received intravenous prophylactic TXA and those who underwent surgery without TXA. Statistical analysis was performed with Student t test and the Mann-Whitney U test for nonparametric results. We identified 206 patients who underwent craniosynostosis surgery over an 8 year period; 78 control patients and 128 patients that received TXA. Tranexamic acid was found to result in a weight-adjusted calculated blood loss mean difference of 9.6 ml/kg across all procedures (P = 0.0332 95% confidence interval 0.7734-18.4266). The actual blood loss reduction achieved with TXA was 6.7 ml/kg in spring cranioplasties, compared to 15.2 ml/kg in fronto-orbital remodeling procedures. There was a statistically and clinically significant reduction in postoperative transfusion incidence, with transfusions required in 27% of controls and 6% of TXA patients (P

Blood loss is a potential cause of morbidity and mortality in craniosynostosis surgery. Recent reports have suggested that the use of tranexamic acid (TXA), an antifibrinolytic agent, mitigates this blood loss. A comprehensive systematic review and subsequent meta-analysis was undertaken, with the view to clarify the effectiveness of TXA in reducing blood loss and transfusion requirements in craniosynostosis surgery. Medline and PubMed databases were searched using the preferred reporting items for systematic reviews and meta-analyses technique, and 7003 articles were assessed based on predefined selection criteria. Seven trials were identified, of which 2 were randomized controlled trials and the remainder retrospective cohort studies. All trials were assessed using the Jadad and strengthening the reporting of observational studies in epidemiology scores. The meta-analysis found a clear statistical reduction in blood loss in those patients who received TXA perioperatively, with a combined blood loss reduction of 7.06 ml/kg (95% confidence interval -8.97 to -5.15, P

Liposuction remains one of the most frequently performed cosmetic surgical procedures and its popularity is increasing every year. However, since its inception, justified concerns regarding patient safety have placed limits on the volume of fat that can be aspirated, influenced by hemodynamic fluctuations and blood loss during liposuction. Tranexamic acid (TXA) is an antifibrinolytic agent that competitively inhibits the conversion of plasminogen to plasmin, thus preventing the binding and degradation of fibrin. Despite the existence of evidence of the effectiveness of TXA in orthopedic and cardiac surgeries, there is little evidence of its use in liposuction. The objective of this study was to evaluate the efficacy and safety of tranexamic acid in the control of surgical bleeding in patients undergoing liposuction, through a prospective, open, randomized and controlled clinical trial. Two groups of 25 participants each were formed to whom the application of TXA in a tumescent solution prior to liposuction or liposuction with the traditional technique was randomly assigned. The results showed a decrease in blood loss reflected by the differences in the final hematocrit values, as well as decrease in the same per aspirated volume (p = 0.003). No adverse events were found related with the TXA application and no blood transfusions were required in this group, in contrast to the control group where the need for blood transfusion was present in 20% of the intervened participants. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

BACKGROUND This study aimed to investigate the effect of intravenous tranexamic acid (TXA) on blood loss and transfusion rates in children who underwent resection and endoprosthetic reconstruction of distal femoral osteosarcomas. METHODS The medical records of 56 patients who underwent resection and endoprosthetic reconstruction for distal femoral osteosarcomas between 2017 and 2019 were retrospectively reviewed. Patients were divided into 2 groups: group 1 consisted of 25 patients (11 male and 14 female, mean age 15.2±3 y) who received preoperative 15 mg/kg intravenous TXA, and group 2 consisted of 31 control patients (18 male and 13 female, mean age 14.3±2.6 y) who did not receive TXA. The groups were compared based on their total blood loss, intraoperative blood loss, hidden blood loss, postoperative drain output, transfusion requirements, preoperative and postoperative hemoglobin (Hb) and hematocrit (Htc) difference, length of hospital stays, operative time, and complications. RESULTS The mean total blood loss was lower in intravenous TXA group (1247.5±300.9 mL) when compared with control group (1715.7±857.0 mL) (P=0.018). The mean intraoperative blood loss in intravenous TXA group (386±109 mL) was lower than that in control group (977.4±610.7 mL) (P

Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure‐related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post‐procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis.

Hereditary hemorrhagic telangiectasia (HHT) management is evolving because of the emergence and development of antiangiogenic therapies to eliminate bleeding telangiectasias and achieve hemostasis. This progress is reflected in recent clinical recommendations published in the Second International Guidelines for the Diagnosis and Treatment of HHT, in which systemic therapies including antiangiogenics and antifibrinolytics are now recommended as standard treatment options for bleeding. This review highlights the new recommendations especially relevant to hematologists in managing bleeding, anticoagulation, and anemia in patients with HHT.

Tranexamic acid (TXA) is a lysine analogue that inhibits plasmin generation and has been used for decades as an antifibrinolytic agent to reduce bleeding. Recent reports have indicated that TXA can paradoxically promote plasmin generation. Blood was obtained from 41 cardiac surgical patients randomly assigned to TXA or placebo before start of surgery (preOP), at the end of surgery (EOS), then again on postoperative day 1 (POD-1) as well as POD-3. Plasma levels of tissue-type plasminogen activator (t-PA), urokinase (u-PA), the plasmin-antiplasmin (PAP) complex, as well as t-PA and u-PA-induced clot lysis assays were then determined. Clot lysis and PAP complex levels were also assessed in healthy volunteers before and at various time points after taking 1 g TXA orally. Surgery induced an increase in circulating t-PA, yet not u-PA at EOS. t-PA levels were unaffected by TXA; however, u-PA levels were significantly reduced in patients on POD-3. t-PA and u-PA-induced clot lysis were both inhibited in plasma from TXA-treated patients. In contrast, PAP complex formation, representing plasmin generation, was unexpectedly enhanced in the plasma of patients administered TXA at the EOS time point. In healthy volunteers, oral TXA effectively blocked fibrinolysis within 30 min and blockade was sustained for 8 h. However, TXA also increased PAP levels in volunteers 4 h after administration. Our findings demonstrate that TXA can actually augment PAP complex formation, consistent with an increase in plasmin generation in vivo despite the fact that it blocks fibrinolysis within 30 min. This may have unanticipated consequences in vivo.

Tranexamic acid (TXA) has become a commonly used perioperative intervention in total joint arthroplasty, shoulder and knee arthroscopy, and spinal procedures in order to minimize blood loss, hematoma formation, hemarthrosis, and wound healing complications. There is a potential role for TXA use in foot and ankle procedures, with limited studies suggesting a potential benefit in minimizing postoperative wound complications and blood loss without an increased risk of thromboembolic events. In light of the profound clinical and financial impact of TXA use in other orthopaedic subspecialties and the early successes in foot and ankle surgery, we aim to provide more information about TXA and its use in foot and ankle surgery. Therefore, the purpose of this review is to perform a comprehensive literature review on the topic of TXA use in foot and ankle procedures in order to describe the pertinent available literature on the use of TXA in orthopaedic surgery and its implications specifically in foot and ankle surgery. It is our aim to identify potential benefits and shortcomings in the available evidence on TXA use for foot and ankle surgery in hopes to (1) best inform foot and ankle surgeons where beneficial and safe and (2) inspire further research on this topic as it relates to clinical management for foot and ankle patients. Levels of Evidence: Level IV

Introduction and objectives The role of the anesthesiologist in the perioperative management of hemostasis has attracted increasing attention. The fibrinolytic system participates in hemostasis, removing clots after repair of the vascular injury. Over the past two decades, several studies have assessed the efficacy and safety of antifibrinolytic agents in reducing perioperative bleeding and transfusion requirements. Some of the conditions that seem to benefit from antifibrinolytic drugs involve trauma, postpartum hemorrhage, cardiac surgery, spine surgery, knee or hip arthroplasty, urological and gynecological surgery, among others. However, there are currently few publications focusing on the perioperative features of fibrinolytic system, which will be the subject of the present review. Content and conclusions Fibrinolytic physiology, its relationship with the clot structure and its perioperative behavior are described. Pathophysiological mechanisms related to anesthesiology clinical practice and their possible perioperative scenarios are addressed according to a suggested classification. This article aims to provide anesthesiologists with a broader understanding of the normal functioning of fibrinolysis, the mechanisms of possible deviations from normality in the perioperative period, the pathophysiological rationale supporting the current indications of antifibrinolytics, and some recent outcomes obtained with their use.

Background: Pediatric patients are at risk for bleeding after cardiac surgery. Administration of antifibrinolytic agents reduces postoperative blood loss. Objective: Evaluation of the efficacy of combined administration of tranexamic acid (TXA) and ethamsylate in the reduction of postoperative blood loss in pediatric cardiac surgery. Methods: This prospective randomized study included 126 children submitted for cardiac surgery, and they were allocated into three groups: control group (n = 42); TXA group (n = 42):- received only TXA; and combined ethamsylate TXA group (n = 42):- received a combination of TXA and ethamsylate. The main collected data included sternal closure time, the needs for intraoperative transfusion of blood and its products, the total amount of blood loss, and the amount of the whole blood and its products transfused to the patients in the first 24 postoperative hours. Results: Blood loss volume in the first 24 postoperative hours was significantly smaller in combined group than the TXA and control groups and was significantly smaller in the TXA group than the control group. The sternal closure time was significantly shorter in the combined group than the other 2 groups and significantly shorter in TXA than the control group. The amount of whole blood transfused to patients in the combined group during surgery and in the first postoperative 24 h was significantly smaller than the other 2 groups and smaller in TXA group than the control group during surgery. Conclusion: Combined administration of ethamsylate and TXA in pediatric cardiac surgery was more effective in reducing postoperative blood loss and whole blood transfusion requirements than the administration of TXA alone.

Functional endoscopic sinus surgery (FESS) requires good intraoperative surgical field visualization for better identification of structures. Among the many modalities for improving visibility, antifibrinolytic agent like Tranexamic acid has shown good results in many other surgeries. In this study, we have evaluated the effect of a single bolus dose of 15mg/kg intravenous Tranexamic acid when used as an adjunct. Materials and Methods: We have studied group T (n=30), who received Inj. Tranexamic acid against group C (n=30) i.e. control group. They were compared for surgical field using Boezaart scale, surgical duration and blood loss. Statistical analysis was done by unpaired t test and chi square test as was appropriate. Results: T group showed significantly lower values of Boezaart scale score i.e. better visualisation for surgical field (p Conclusion: We found that Tranexamic acid has a beneficial role in functional endoscopic sinus surgeries by improving the quality of surgical field when used as an adjunct. Keywords: Tranexamic acid, surgical field, functional endoscopic sinus surgery.

O angioedema familiar, desordem genética com produção exacerbada de bradicinina e edema generalizado, tem sintomas diversos que surgem sem nenhum fator causal. O tratamento consiste no uso de medicações de resgate durante as crises e na profilaxia a curto e longo prazo. Objetivo: relatar o caso de um paciente tratado com ácido tranexâmico, um agente antifibrinolítico, que apresentou elevação de ureia, creatinina e creatina fosfoquinase, recebendo o diagnóstico de injúria renal aguda por rabdomiólise. Após suspensão do medicamento, melhorou a função renal e diminuiu a enzima. Conclusão: a rabdomiólise é um efeito descrito com o uso do ácido épsilon-aminocaproico, mas não do ácido tranexâmico.

Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage.We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of7, intracerebral haemorrhage volume70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (33% relative or6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636).Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified.National Health and Medical Research Council, Royal Melbourne Hospital Foundation.

OBJECTIVE This was a retrospective, cohort study investigating the efficacy and safety of continuous low-dose postoperative tranexamic acid (PTXA) on drain output and transfusion requirements following adult spinal deformity surgery. METHODS One hundred forty-seven patients undergoing posterior instrumented thoracolumbar fusion of ≥ 3 vertebral levels at a single institution who received low-dose PTXA infusion (0.5-1 mg/kg/hr) for 24 hours were compared to 292 control patients who did not receive PTXA. The cohorts were propensity matched based on age, sex, American Society of Anesthesiologist physical status classification, body mass index, number of surgical levels, revision surgery, operative duration, and total intraoperative TXA dose (n = 106 in each group). Primary outcome was 72-hour postoperative drain output. Secondary outcomes were number of allogeneic blood transfusions. RESULTS There was no significant difference in postoperative drain output in the PTXA group compared to control (660 ± 420 mL vs. 710 ± 490 mL, p = 0.46). The PTXA group received significantly more crystalloid (6,100 ± 3,100 mL vs. 4,600 ± 2,400 mL, p < 0.001) and red blood cell transfusions postoperatively (median [interquartile range]: 1 [0-2] units vs. 0 [0-1] units; incidence rate ratio [95% confidence interval], 1.6 [1.2-2.2]; p = 0.001). Rates of adverse events were comparable between groups. CONCLUSION Continuous low-dose PTXA infusion was not associated with reduced drain output after spinal deformity surgery. No difference in thromboembolic incidence was observed. A prospective dose escalation study is warranted to investigate the efficacy of higher dose PTXA.

Background Tranexamic acid (TXA) is an antifibrinolytic agent. It has long been used to reduce the need for perioperative blood loss in various surgeries. Few studies have investigated the effects of local and intravenous administration of TXA on fracture healing. Thus, we aimed to evaluate if TXA influences hematoma volume and fracture healing in the rat tibia fracture model. Materials and methods A tibia fracture with intramedullary Kirschner wire fixation was created in all animals. Rats were randomly divided into three groups as local TXA, intravenous TXA, and control. A dose of 50 mg/kg local and intravenous TXA was administered to the study groups. Hematoma volume was measured on the first and third days of the study. The animals were sacrificed on the 14th and 21st days for radiological and histopathological examinations. Results There was no significant difference between the groups in terms of hematoma volume measured on Day 1 and the mean decrease of hematoma volume from Day 1 to Day 3 (p = 0.158 and p = 0.239, respectively). The total radiological scores of Day 14 and Day 21 were similar in all groups (p > 0.05 for all). There was also no significant difference between the histological staging of the fracture repair on Day 14 and Day 21 for all groups (p > 0.05 for all). Conclusion Our findings suggest that TXA's local and intravenous application makes no significant difference in fracture healing.

Surgical bleeding may lead to the need for blood transfusion and minimizing blood loss has been a basic principle followed by surgeons for generations. Antifibrinolytic agents are widely used to reduce perioperative haemorrhage. The present study sought to assess the efficacy of directly infiltrated tranexamic acid in ameliorating bruising in participants undergoing cosmetic plastic surgery (liposuction). The study employed a blinded, prospective, randomized, case control design. Thirty-three patients were studied. Tranexamic acid free infiltration tumescent solution (saline, bupivacaine lignocaine and adrenalin) was infiltrated to one flank of patients undergoing liposuction of flanks. The other flank was infiltrated with the same tumescent solution (saline, bupivacaine lignocaine and adrenalin) mixed with tranexamic acid (0.1%). Bruises were photographed one and seven days after surgery and measured for size. The surface area of the bruises was calculated using ImageJ software. We compared the bruised surface are between the tranexamic acid infiltrated flank and non-tranexamic acid infiltrated flank in the same patient. The model employed involved measuring the bruises on each flank of the same patient, with surgery by a single surgeon using the same infiltration and surgical techniques for both sides. The only variable was the difference in tranexamic acid concentration between study and control flanks. We found that use of tranexamic acid consistently resulted in a smaller bruise area on days one and seven after liposuction of flanks. Results were statistically significant. This is the first study examining addition of tranexamic acid to a tumescent infiltration solution—to produce a predictable local concentration of tranexamic acid—in order to maximize surgical site effect and minimize systemic effect. The authors recommend incorporation of tranexamic acid as a routine component along with adrenaline and local anaesthetics in tumescent field infiltration solution 10–15 min before commencement of the cosmetic surgery. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hematoma is the most common complication in facelift surgery. It has a reported incidence ranging from 0.2 to 8%. Tranexamic acid (TXA) is an antifibrinolytic agent capable of minimizing blood loss, and its use in plastic surgery is quite new. The literature review indicates that there are no formal guidelines for dosing and standardization of TXA use. We sought to evaluate the efficacy of intraoperative local irrigation of TXA in reducing the incidence of hematomas in patients undergoing facelift surgery. A prospective cohort observational comparative study was conducted between November 2018 and November 2019 with 30 patients undergoing primary facelift surgery at the Ivo Pitanguy Institute in Rio de Janeiro, Brazil. The participants were divided into two groups: group I, patients who underwent facelift with 2.5% topical TXA irrigation as a new routine of the service, and group II, patients who underwent facelift without topical TXA irrigation as a routine. Drainage output in the first 24 h, hematoma formation, and complication rate were evaluated. It was found that local intraoperative TXA irrigation reduces drainage output in the first 24 h by 71% compared with group II (median 10 ml (8–22 ml) versus 35 ml (19–50 ml); p = 0·009). The rate of postoperative complications (p = 0.1) and hematoma (p = 0.08) was lower in the group with intraoperative local irrigation with TXA. This was not statistically significant. Local TXA irrigation seems to decrease bleeding and has been shown to be effective in reducing drainage output in the first 24 h postoperatively. Level of evidence: Level III, risk / prognostic study.

Preoperative blood loss is common in total knee replacement. Tranexamic acid can reduce active bleeding. It is the most effective antifibrinolytic agent available. Our objective was to compare the efficacy of tranexamic acid in controlling perioperative blood loss in adult patients undergoing total knee replacement using intravenous versus intraarticular route. An analytical cross-sectional study was conducted on 95 patients who underwent total knee replacement surgery in our institution. Patients were selected for intravenous (group A) and intra articular (group B) by simple randomization. During the postoperative period, the amount of blood in the drain and post-operative hemoglobin at 48 hours were collected and total blood loss was calculated. Mean pre-operative hemoglobin in group A was 11.73 and in group, B was 11.86. Average blood loss in the drain was 305 ml and 293 ml in group A and group B respectively. Average total blood loss was 464ml and 438 ml in group A and B respectively. Average fall in Hb was 0.69 and 0.80 in group A and group B respectively at 48hours. One patient in each group was transfused with allogeneic blood. There were no clinically evident DVT cases in either group. In conclusion, both intraarticular and intravenous tranexamic acid were found to be equally effective in controlling perioperative blood loss in total knee arthroplasty patients with no significant increase in thromboembolic complications.

International audience; Fast acting topical hemostatic agents play a key role in hemorrhage control. Retarding fibrinolysis is also critical in improving coagulation, thereby expanding chances of survival. The purpose of the present work was to investigate the physical properties, loading capacity and hemostatic efficacy of newly developed nanoclay microsphere frameworks (NMFs) loaded with tranexamic acid (TA), as antifibrinolytic agent. Nanoclay compositions were prepared with increasing levels of TA. Results showed that TA was successfully incorporated into the nanoclay structure and released when solvated with ethanol. Both doped and undoped NMFs significantly decreased activated partial thromboplastin time and increased clot stiffness, which was attributed to significantly thinner fibrin fibers and a denser clot structure.

Background Tranexamic acid (TXA), an antifibrinolytic drug, is usually administered intravenously; however, intra-articular administration has recently been proven to be as effective as intravenous administration. Limited information regarding the pharmacokinetics (PK) of TXA after intra-articular administration has been reported. Aims The aim of this study was to develop a population PK model of TXA administered as a single intra-articular dose and as two intravenous doses, and to study the sources of interindividual variability (IIV) in the PK processes of TXA. The developed model was used to simulate PK profiles of TXA at different dosage regimens and in patients with renal impairment. Methods Patients who underwent primary unilateral total knee replacement (TKR) received 1 g/10 mL (concentration of 100 mg/mL) of TXA applied directly to the surgical field before wound closure, or 2 g (two doses of 1 g) of intravenous TXA. A population PK model was developed using a nonlinear mixed-effects approach and sources of IIV, such as sex, age, body weight, height, body mass index (BMI), preoperative haemoglobin, preoperative haematocrit, and creatinine clearance. Results Twenty-four patients were included, 12 in each group. Twenty patients were female, mean age (standard deviation) was 73.7 years (5.6). The disposition of TXA was best described as a two-compartment model with clearance dependent on creatinine clearance. Bootstrap results indicated that the model was stable and robust. The estimated bioavailability for intra-articular administration was 81%. Simulations indicated that 100% of patients would have plasma concentrations associated with partial fibrinolysis at 8 h post-administration with the dosages and routes of administration used in the present study. Intra-articular administration would produce complete inhibition of fibrinolysis in only 12% of patients compared with 72.5% with intravenous administration. No adverse events were reported. Conclusions This population PK model demonstrated that a single dose of high-concentration, low-volume intra-articular TXA can achieve antifibrinolytic plasma concentrations of the drug for 8 h, providing both local and systemic effects in patients undergoing TKR. TXA administration to the surgical field could be an alternative to the intravenous; route for patients undergoing TKR; however, clinical studies are needed to assess the toxic local effects of TXA.

RationaleHaematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.Methods and designStopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.HypothesisIn patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimatesA sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.InterventionParticipants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.Primary efficacy measureThe primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.DiscussionWe describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.

Background: Tranexamic acid (TXA) reduces blood loss and transfusion requirements during craniosynostosis surgery in small children. Possible interaction from TXA on the inflammatory system is unknown. Objective: To evaluate the effect of TXA on a wide range of inflammatory markers in children receiving TXA in a randomized, blinded, and placebo controlled study design. Methods: Thirty children undergoing craniosynostosis surgery with significant blood loss received TXA (bolus dose of 10 mg kg−1 followed by 8 hours continuous infusion of 3 mg kg−1 h−1) or placebo in a randomized, double-blinded study design. Using a new proximity extension assays employing a panel of inflammatory biomarkers samples was used for analysis of blood samples obtained pre-operatively, 4 and 24 hours after operation. Results: Ninety-two inflammatory parameters were measured. TXA did not affect any of the measured parameters as compared with placebo. Among 34 of the 92 pro- and antiinflammatory parameters investigated changes were observed between pre-operative, 4 or 24 hours, respectively, reflecting immune activation during surgical stress. Conclusion: TXA administration in a low-dose regimen including bolus followed by 8 hours infusion during craniosynostosis surgery did not change any of 92 inflammatory markers as compared with placebo.

Melasma, a common cause for seeking dermatologic care, is a chronic condition of skin hyperpigmentation. With a poorly understood pathogenesis, and no universal cure, melasma is a challenge for many dermatologists. For decades, there has been investigation into the role of oxidative stress in melasma. In this literature review, we introduce the role of oxidative stress in melasma and discuss the function of various topical and oral antioxidant therapies for patients suffering from melasma. Numerous studies have shown efficacy of various antioxidant therapies for treatment of hyperpigmentation, and in this review, we focus primarily on those with less widespread use. Vitamin E, niacinamide, polypodium leucotomos, pycnogenol, grape seed extract, amino fruit acids, phytic acid, zinc, silymarin, Korean red ginseng powder, plant extracts, and parsley all have well-demonstrated evidence of antioxidant properties, and these substances have been studied in the context of skin hyperpigmentation. Although there is conflicting evidence of their therapeutic efficacy, the use of these naturally occurring substances is promising for patients and medical providers seeking alternative therapeutic options.

Background Hereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited disorder characterized by development of mucocutaneous telangiectases and visceral organ arteriovenous malformations, which can lead to recurrent, spontaneous bleeding and development of iron deficiency anemia. The primary objective of this study was to ascertain the relationship between epistaxis severity scores (ESS), laboratory values, genotype, and phenotype in HHT. Our secondary objective was to assess efficacy of systemic antifibrinolytic therapy in reducing ESS in HHT. Methodology We conducted a retrospective review of patients seen at the UNC HHT Center from January 1, 2009 to February 28, 2015. ESS, demographics, and results of genetic testing were abstracted from the medical record. Response to antifibrinolytic therapy was evaluated by comparing pre-post ESS. Results One hundred and forty nine patients were eligible with 116 having genetic testing and 33 without. Age, hemoglobin and ferritin levels were predictive of ESS. Of the 116 patients that underwent genetic testing: 63 had an ACVRL1 mutation, 40 had an ENG mutation, 2 had a SMAD4 mutation, and 11 patients had no pathologic HHT genetic variation detected. Compared to patients without a detectable HHT-associated genetic variation, patients with a HHT-associated genetic variation had higher ESS scores (p 4 were started on antifibrinolytic therapy (tranexamic acid or aminocaproic acid) and had a post-treatment ESS recorded. All patients had a decrease in ESS of > 0.71 (minimal meaningful difference), but patients taking antifibrinolytics displayed larger decreases. No patients on antifibrinolytics experienced a VTE with median follow up of 13 months. Conclusions We demonstrate that the ESS correlates with age, hemoglobin and ferritin. Additionally, we demonstrate that HHT patients with genetic mutations have higher ESS scores. Our data demonstrate that antifibrinolytics are effective in decreasing epistaxis severity and safe with long-term use in HHT patients.

Background: Total knee arthroplasty is associated with significant peri-operative blood loss. Various studies have shown that the use of tranexamic acid reduces post-operative blood loss and need for allogeneic blood transfusion in total knee arthroplasty. Objectives: To assess the effect of tranexamic acid in the reduction of the postoperative blood loss in total knee arthroplasty. Methodology: An analytical cross-sectional study was carried out in 14 patients who underwent primary total knee arthroplasty during the study period of 12 months at Kathmandu Medical College. Seven patients were allocated to the case group and received one gram (gm) of tranexamic acid thirty minutes prior to the incision and five hundred milligram (mg) orally three times a day till the drain was removed. Tranexamic acid was not given to the seven patients in control group. The haemoglobin of the patient was recorded on the day of surgery and the total amount of drain output was recorded on postoperative period until the drain was removed. Results: Out of 14 patients operated, it was found that the average amount of drain in the patients in case group was 628 ± 234 millilitre (ml) which was significantly lower than the control group 1028 ± 183 ml (p

Almost two-thirds of patients with severe traumatic brain injury (TBI) develop some form of hemostatic disturbance, which contributes to poor outcome. While the initial head injury often leads to impaired clot formation, TBI is also associated with an increased risk of thrombosis. Most likely there is a progression from early bleeding to a later prothrombotic state. In this paper, we systematically review the literature on the time course of hemostatic disruptions following TBI. A MEDLINE search was performed for TBI studies reporting the trajectory of hemostatic assays over time. The search yielded 5,049 articles, of which 4,910 were excluded following duplicate removal as well as title and abstract review. Full-text assessment of the remaining articles yielded 33 studies that were included in the final review. We found that the first hours after TBI are characterized by coagulation cascade dysfunction and hyperfibrinolysis, both of which likely contribute to lesion progression. This is then followed by platelet dysfunction and decreased platelet count, the clinical implication of which remains unclear. Later, a poorly defined prothrombotic state emerges, partly due to fibrinolysis shutdown and hyperactive platelets. In the clinical setting, early administration of the antifibrinolytic agent tranexamic acid has proved effective in reducing head-injury-related mortality in a subgroup of TBI patients. Further studies evaluating the time course of hemostatic disruptions after TBI are warranted in order to identify windows of opportunity for potential treatment options. Electronic supplementary material The online version of this article (10.1007/s12028-020-01037-8) contains supplementary material, which is available to authorized users.

Author(s): Boccio, Eric; Hultz, Kyle; Wong, Ambrose H. | Abstract: Introduction: Tranexamic acid (TXA) is an antifibrinolytic agent currently approved and utilized in the treatment of dysfunctional uterine bleeding, traumatic extracranial hemorrhage, anterior epistaxis, and dental procedures on patients with hemophilia. There is a paucity of literature evaluating the use of TXA for hemostasis in patients on direct oral anticoagulants (DOACs).Case Report: Our patient, a 72 year-old male on rivaroxaban, presented with persistent bleeding following a punch biopsy of the buccal mucosa. Given the site of bleeding, inability to effectively tamponade, patient’s anticoagulated state, and risk of impending airway compromise, a dressing was soaked with 500 milligram (mg) of TXA and was held in place with pressure using a makeshift clamp until a thrombus formed. Hemostasis was achieved preventing the need for acute ENTotolaryngologic intervention and/or intubation. The patient was observed in the medical setting overnight and discharged home without any recurrence of bleeding or adverse events.Discussion: This case report describes our experience achieving hemostasis for an otherwise uncontrollable oral bleed in an anticoagulated patient on a DOAC who could not be reversed. Intervention is simple to perform, cost-effective, and requires few resources which are readily available in most emergency departments.Conclusion: We report a novel application of TXA to control an oral mucosal bleed in an anticoagulated patient which was on a DOAC refractory to traditional measures.

Introduction Endoprosthetic reconstruction presents a significant risk of perioperative blood loss. Tranexamic acid (TXA) is an antifibrinolytic agent used to reduce blood loss in orthopaedic procedures. The safety and efficacy of TXA in arthroplasty are well documented. There is, however, a dearth of literature exploring the safety and efficacy of TXA in musculoskeletal oncology patients. This retrospective, comparative study explores the effects of TXA on perioperative blood loss, blood transfusion rates, venous thromboembolism (VTE) occurrence, and hospital stay in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction. Methods For the study, charts from a total of 90 patients who underwent resection of an aggressive bone tumor and endoprosthetic reconstruction were reviewed; of these patients, 34 were in the TXA group and 56 in the non-TXA group. Study participants composed of a heterogeneous group of patients with primary bone sarcoma and metastatic osseous disease. Patients in the TXA group received 1 g of topical TXA administered into the wound bed before closure. The Hemoglobin Balance method was used to calculate blood loss. Patients were followed for 6 weeks. Results Patients undergoing proximal femur replacement and distal femur replacement in the TXA group experienced a 796 and 687 mL reduction in 72-hour mean blood loss, respectively (P = 0.0003 and P = 0.006). Average blood transfusions decreased by 0.45 U of packed red blood cells per patient in the TXA group (P = 0.048) and transfusion incidence decreased by 21.1% compared with the non-TXA group (P = 0.04). Patients undergoing proximal femur replacement in the TXA group left the hospital 2.2 days earlier than those in the non-TXA group (P = 0.0004). No increase in VTE rate was observed with TXA use. Discussion This study found results similar to total joint arthroplasty with regard to TXA's effect on perioperative blood loss, transfusion rates, hospital stay, and VTE occurrence. It provides initial data to support the efficacy of topical TXA use in this patient cohort. Level of evidence Level III, retrospective cohort study.

Background and importance Superior cerebellar artery (SCA) perforator aneurysms are extremely rare, with only one other case published in the literature. There is no conclusive management strategy for these aneurysms, although endovascular treatment, open surgical treatment with clipping, and antifibrinolytic administration with spontaneous thrombosis have all been discussed. Clinical presentation A 61-yr-old male presented with intraventricular hemorrhage (IVH) primarily in the posterior fossa. He was found to have a dissecting left SCA perforator aneurysm lying on the floor of the fourth ventricle. The aneurysm was not amenable to endovascular treatment, and antifibrinolytic therapy failed to spontaneously thrombose the aneurysm. We performed a suboccipital craniotomy and used a supracerebellar transvermian approach to resect the aneurysm. There was total obliteration of the aneurysm on postoperative cerebral angiogram. Conclusion SCA perforator aneurysms represent an extremely uncommon subset of intracranial aneurysms. The best therapeutic strategy has yet to be definitively proven. When pursuing surgical treatment, the supracerebellar transvermian navigated approach can be a useful and safe option, as described and illustrated in this video.

Study design Retrospective cohort. Objective To evaluate the effectiveness and safety of antifibrinolytic (AF) agents in reducing perioperative blood transfusion in pediatric patients undergoing spinal fusion. Summary of background data The potential for AF to decrease bleeding and reduce exposure to allogenic transfusions has led to widespread off-label use in a number of major pediatric surgical procedures. Recent reviews call for improving the body of evidence for their effectiveness and safety in pediatric spinal fusion. Methods Children undergoing spinal fusion were identified in the American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP-P) 2016 and 2017 databases. Univariate analyses of patient and perioperative characteristics informed the creation of a propensity score model predicting treatment with AF, followed by 1:1 matching to allow comparison of allogenic red blood cell transfusion rates and secondary outcomes between treated and untreated patients. Results Of 6626 total patients, 5434 (81%) received AF and 1533 (23%) received a blood transfusion. Analysis of data for 1192 propensity score-matched pairs revealed that treatment with AF was associated with a statistically non-significant 16% reduction in perioperative transfusion (OR 0.84, 95% confidence interval 0.68-1.05, p = 0.119) and a statistically significant 43% reduction in postoperative transfusion (OR 0.57, 95% confidence interval 0.39-0.81, p = 0.002). No differences in the incidences of postoperative seizure or thrombosis were observed, with overall rates of 7.5 and 22.5 events per 10,000 patients, respectively. Conclusions AF agents appear to reduce postoperative allogenic transfusion in children undergoing spinal fusion surgery. Adverse drug effects such as thromboembolic complications and seizure were extremely rare and warrant continued monitoring, though this is the largest study to date providing evidence for the safety profile of these drugs. Level of evidence 3.