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.

Peroperative administration of tranexamic acid in Roux-en-Y and one-anastomosis gastric bypass to reduce haemorrhage in patients with morbid obesity: protocol for randomised controlled trial (PATRY trial).

INTRODUCTION: By implementation of Enhanced Recovery After Bariatric Surgery protocols and day-care surgery, early discharge poses a challenge if excessive bleeding occurs after bariatric surgery. Tranexamic acid (TXA) has demonstrated efficacy in other surgical fields and in bariatric pilot studies. This trial aims to assess the efficacy of peroperative administration of TXA in reducing haemorrhage in patients undergoing gastric bypass surgery. METHOD AND ANALYSIS: This is a multicentre, phase III, double-blind randomised controlled trial in six high-volume bariatric centres in the Netherlands. A total of 1524 eligible patients, aged 18 years or older, undergoing primary gastric bypass surgery (either Roux-en-Y gastric bypass or one-anastomosis gastric bypass) will be randomised between TXA and placebo (1:1, variable block, stratified for centre, day-care/overnight stay and type of surgery) after obtaining informed consent (2.5% less haemorrhage, power 80%, 2-sided-α 0.05 and 10% dropout). Exclusion criteria are pregnancy, amedical history of acute bleeding (without cause), venous thrombotic events (VTEs), epilepsy, anticoagulant use and iatrogenic bleeding during surgery (aside from staple line). The primary outcome is postoperative haemorrhage requiring intervention within 30 days postoperatively. Secondary outcome measures are staple line reinforcement, blood loss, duration of surgery, postoperative haemoglobin, vital parameters, minor and major complications, side effects of TXA (nausea, hypotension and VTE), length of hospital stay and directly made costs. ETHICS AND DISSEMINATION: Written informed consent will be obtained from all participants. The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 7 February 2023 (registration number: R22.102). Results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT05464394.

Tranexamic Acid and Tourniquet: Which Combination Reduces Blood Loss Most Effectively?

BACKGROUND: Blood loss during and after total knee arthroplasty (TKA) can lead to substantial morbidity and the need for blood transfusions. There are several methods to minimize blood loss and decrease transfusion rates in patients undergoing TKA. Tranexamic acid, an antifibrinolytic agent with known efficacy for achieving these goals, is combined with tourniquets to reduce bleeding in arthroplasty surgeries. Our study investigated the effects of various combinations of tranexamic acid and tourniquet use on bleeding in knee arthroplasty in 558 patients. AIM: We aimed to determine the method that would provide the least blood loss and transfusion need in knee arthroplasty surgery. METHODS: Between January 2018 and December 2022, 558 patients aged between 55 and 85 years underwent TKA surgery for grade 4 gonarthrosis in our clinic, and their decrease in hemoglobin value and whether they were transfused or not were analyzed. The patients were divided into four groups based on use of tranexamic acid and tourniquet. Demographic variables and patient data (body mass index, INR values, and preoperative hemoglobin values) were recorded. RESULTS: There were 558 patients with a mean age of 68.19 (67 ± 6.949) years. In group 1, tranexamic acid was not used in 128 patients and tourniquet was used only during cementation; in group 2, in 132 patients, tranexamic acid was not used and tourniquet was used throughout the surgery; in group 3, in 158 patients, tranexamic acid was used and tourniquet was used throughout the surgery; in group 4, in 140 patients, tranexamic acid was used and tourniquet was used only during cementation. The decrease in hemoglobin value and transfusion rate was lowest in group 3 and highest in group 1. Besides, there was a greater decrease in hemoglobin value in group 2 than in group 4 and the transfusion rate was similar. CONCLUSIONS: This clinical study showed that using tranexamic acid and a tourniquet throughout surgery significantly reduced the decrease in hemoglobin value and the need for transfusion.

Point-of-care testing for tranexamic acid efficacy: a proof-of-concept study in cardiac surgical patients.

BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.

Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair.

BACKGROUND: The role of aprotinin in modern cardiac surgery is not well defined. While licensed for use in isolated coronary artery bypass grafting it is more commonly used for cases deemed to be at an increased risk of bleeding. The relative efficacy, and safety profile, of aprotinin as compared to other antifibrinolytics in these high-risk cases is uncertain. STUDY DESIGN AND METHODS: A retrospective observational study with propensity matching to determine whether aprotinin versus tranexamic acid reduced bleeding or transfusion requirements in patients presenting for surgical repair of type A aortic dissection (TAD). RESULTS: Between 2016 and 2022, 250 patients presented for repair of TAD. A total of 231 patients were included in the final analysis. Bleeding and transfusion were similar between both groups in both propensity matched and unmatched cohorts. Compared to tranexamic acid, aprotinin use did not reduce transfusion requirements for any product. Rates of bleeding in the first 12 h, return to theater and return to intensive care unit with an open packed chest were similar between groups. There was no difference in rates of renal failure, stroke, or death. CONCLUSION: Aprotinin did not reduce the risk of bleeding or transfusion requirements in patients undergoing repair of type A aortic dissections. Efficacy of aprotinin may vary depending on the type of surgery performed and the underlying pathology.

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

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

Tranexamic acid versus adrenaline-soaked pledgets for the reduction of intraoperative bleeding in functional endoscopic sinus surgery.

OBJECTIVE: Aim: To examine the impact of locally applied tranexamic acid and adrenaline, separately and in combination, on intraoperative blood loss and surgical field quality during functional endoscopic sinus surgery. PATIENTS AND METHODS: Materials and Methods: The study involved 40 patients with chronic rhinosinusitis. They were divided into two groups. Group I received adrenaline alone in one side and a mixture of adrenaline and tranexamic acid in the other side. Group II received adrenaline alone in one side and tranexamic acid in the otherside. Parameters like surgery time, blood loss, and surgical field quality were studied. RESULTS: Results: In Group I, the combination of adrenaline and tranexamic acid significantly reduced blood loss and enhanced surgical field quality compared to adrenaline alone. In Group II, adrenaline outperformed tranexamic acid in shortening surgery duration and improving surgical field quality. However, there was no significant difference in blood loss reduction between adrenaline and tranexamic acid. CONCLUSION: Conclusions: The study concluded that tranexamic acid is less effective than adrenaline when introduced as topical intranasal pledgets in both decreasing the time needed for the surgery and improving the subjective satisfaction of the surgeon while there is no significant difference regarding decreasing intraoperative blood loss. The mixture of adrenaline and tranexamic acid pledgets are more effective than adrenaline-only pledgets in terms of decreasing the intraoperative blood loss and improving the surgeon's satisfaction with no significant difference regarding the time needed for the surgery.

Optimised fast-track protocols in total knee arthroplasty determine shorter hospitalisation time and lower perioperative/postoperative complications.

PURPOSE: This literature review aims to present evidence-based clinical recommendations for the eight most debated topics related to perioperative management in total knee arthroplasty: counselling, prehabilitation, transfusion risk, tranexamic acid, drainage, analgesia, urinary catheter and compression stockings. METHODS: A multidisciplinary team conducted a systematic review on these topics. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the literature review and result presentation. The research encompassed articles from 1 January 2009 to 28 February 2023, retrieved through the MEDLINE database via PubMed, Embase database and Cochrane Library. RESULTS: Forty-five articles were selected. Preoperative counselling has limited evidence for its impact on postoperative outcomes; yet, it can help alleviate surgery-related anxiety and manage postoperative symptoms. Prehabilitation can also prepare patients for surgery, reducing hospital stays and improving postsurgery functionality. Numerous studies suggest that preoperative Hb levels are independently linked to transfusion risk, with a recommended level of 13 g/dL. Combining intravenous and local tranexamic acid administration is strongly advised to reduce perioperative blood loss, while drainage after primary total knee arthroplasty offers no functional advantages. Employing a multimodal analgesia approach yields better results with reduced opioid usage. Indwelling urinary catheters provide no benefit and avoiding them can lower the risk of urinary tract infections. As for compression stockings, there is insufficient evidence in the literature to support their efficacy in preventing venous thromboembolism. CONCLUSION: The best-track protocol has demonstrated its efficacy in reducing hospitalisation time and perioperative/postoperative complications. It is success relies on a collaborative, resource-adaptive approach led by a multidisciplinary team. Both patients and hospitals benefit from this approach, as it enhances care quality and lowers costs. Several studies have highlighted the significance of a patient-centred approach in achieving high-quality care. Creating a novel treatment protocol could be a prospective goal in the near future. LEVEL OF EVIDENCE: Level III.

Comparison of blood loss between intra-articular microporous polysaccharide hemospheres powder and tranexamic acid following primary total knee arthroplasty.

Total knee arthroplasty (TKA) is associated with substantial blood loss and tranexamic acid (TXA) effectively reduces postoperative bleeding. Although it is known that there is no difference between intravenous or intra-articular (IA) injection, the general interest is directed towards topical hemostatic agents regarding thromboembolic events in high-risk patients. This study aimed to compare the blood conservation effects of IA MPH powder and TXA in patients undergoing primary TKA. We retrospectively analyzed 103 patients who underwent primary TKA between June 2020 and December 2021. MPH powder was applied to the IA space before capsule closure (MPH group, n = 51). TXA (3 g) was injected via the drain after wound closure (TXA group, n = 52). All patients underwent drain clamping for three postoperative hours. The primary outcome was the drain output, and the secondary outcomes were the postoperative hemoglobin (Hb) levels during the hospitalization period and the perioperative blood transfusion rates. An independent Student's t-test was used to determine differences between the two groups. The drain output in the first 24 h after surgery was significantly higher in the MPH group than in the TXA group. The postoperative Hb levels were significantly lower in the MPH group than in the TXA group. In patients with simultaneous bilateral TKA, there was a significant difference in the blood transfusion volumes and the rates between groups. It is considered that IA MPH powder cannot replace IA TXA because of an inferior efficacy in reducing blood loss and maintaining postoperative Hb levels in the early postoperative period after primary TKA. Moreover, in the case of simultaneous bilateral TKA, we do not recommend the use of IA MPH powder because it was notably less effective in the field of transfusion volume and rate.

Impact of intraosseous regional administration of tranexamic acid in total knee arthroplasty on perioperative blood loss: a protocol for a randomised controlled trial.

INTRODUCTION: Total knee arthroplasty (TKA) is a common surgical intervention to treat joint diseases. However, TKA is associated with significant blood loss. Tranexamic acid (TXA) has been used to reduce perioperative bleeding and postoperative blood transfusion. This study aims to explore the effectiveness and safety of intraosseous regional administration (IORA) of TXA in TKA and compare differences in perioperative blood loss between IORA of TXA, intravenous infusion of TXA, and combined IORA and intravenous infusion of TXA. METHODS AND ANALYSIS: This randomised controlled trial will enrol 105 patients with osteoarthritis who meet the inclusion criteria for unilateral TKA. Patients were randomly divided into three groups using the random number table method. Group A received 1.0 g of TXA via IORA, group B received 1.0 g of TXA via intravenous infusion 15 min prior to the tourniquet release, and group C received both IORA of 1.0 g of TXA and intravenous infusion of 1.0 g of TXA. The primary outcome measure is perioperative total blood loss. Secondary outcomes include bleeding events, venous thromboembolism events, inflammation reactions, other complications and knee function assessments. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Peking Union Medical College Hospital and registered in the Chinese Clinical Trial Registry. Informed consent will be obtained from all the patients before enrolment. The trial will be conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The results of this study will be disseminated through peer-reviewed publications, conference presentations and social media platforms. The findings will provide valuable insights into the use of IORA of TXA in TKA and may lead to the development of new strategies for perioperative blood management in joint replacement surgery. TRIAL REGISTRATION NUMBER: The Ethics Committee of Peking Union Medical College Hospital (approval number: K2371); Chinese Clinical Trial Registry (trial registration number: ChiCTR2200066293).

Prophylactic tranexamic acid for reducing intraoperative blood loss during cesarean section in women at high risk of postpartum hemorrhage: A double-blind placebo randomized controlled trial.

BACKGROUND: Postpartum hemorrhage remains a leading cause of maternal mortality especially in developing countries. The majority of previous trials on the effectiveness of tranexamic acid in reducing blood loss were performed in low-risk women for postpartum hemorrhage. A recent Cochrane Systematic Review recommended that further research was needed to determine the effects of prophylactic tranexamic acid for preventing intraoperative blood loss in women at high risk of postpartum hemorrhage. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of tranexamic acid in reducing intraoperative blood loss when given prior to cesarean delivery in women at high risk of postpartum hemorrhage. STUDY DESIGN: The study is a double-blind randomized controlled trial. METHODS: The study consisted of 200 term pregnant women and high-risk preterm pregnancies scheduled for lower-segment cesarean delivery at Enugu State University of Science and Technology, Teaching Hospital, Parklane, Enugu, Nigeria. The participants were randomized into two arms (intravenous 1 g of tranexamic acid or placebo) in a ratio of 1:1. The participants received either 1 g of tranexamic acid or placebo (20 mL of normal saline) intravenously at least 10 min prior to commencement of the surgery. The primary outcome measures were the mean intraoperative blood loss and hematocrit change 48 h postoperatively. RESULTS: The baseline sociodemographic characteristics were similar in both groups. The tranexamic acid group when compared to the placebo group showed significantly lower mean blood loss (442.94 ± 200.97 versus 801.28 ± 258.68 mL; p = 0.001), higher mean postoperative hemoglobin (10.39 + 0.96 versus 9.67 ± 0.86 g/dL; p = 0.001), lower incidence of postpartum hemorrhage (1.0% versus 19.0%; p = 0.001), and lower need for use of additional uterotonic agents after routine management of the third stage of labor (39.0% versus 68.0%; p = 0.001), respectively. However, there was no significant difference in the mean preoperative hemoglobin (11.24 ± 0.88 versus 11.15 ± 0.90 g/dL; p = 0.457), need for other surgical intervention for postpartum hemorrhage (p > 0.05), and reported side effect, respectively, between the two groups. CONCLUSION: Prophylactic administration of tranexamic acid significantly decreases postpartum blood loss, improves postpartum hemoglobin, decreases the need for additional uterotonics, and prevents postpartum hemorrhage following cesarean section in pregnant women at high risk of postpartum hemorrhage. Its routine use during cesarean section in high-risk women may be encouraged.The trial was registered in the Pan-African Clinical Trial Registry with approval number PACTR202107872851363.

Closed Suction Drainage after Total Knee Arthroplasty with Concomitant Intravenous Tranexamic Acid Administration.

Drain use in total knee arthroplasty (TKA) remains controversial. Use has been associated with increased complications, particularly postoperative transfusion, infection, increased cost, and longer hospital stays. However, studies examining drain use were performed before widespread adoption of tranexamic acid (TXA), which markedly reduces transfusion without increasing venous thromboembolism events. We aim to investigate incidence of postoperative transfusion and 90-day return to the operating room (ROR) for hemarthrosis in TKA with use of drains and concomitant intravenous (IV) TXA. Primary TKAs from a single institution were identified from August 2012 to December 2018. Inclusion criteria were primary TKA, age 18 years and over where use of TXA, drains, anticoagulant, and pre- and postsurgical hemoglobin (Hb) were documented during the patient's admission. Primary outcomes were 90-day ROR specifically for hemarthrosis and rate of postoperative transfusion. A total of 2,008 patients were included. Sixteen patients required ROR, three of which were due to hemarthrosis. Drain output was statistically higher in the ROR group (269.3 vs. 152.4 mL, p = 0.05). Five patients required transfusion within 14 days (0.25%). Patients requiring transfusion had significantly lower presurgical Hb (10.2 g/dL, p = 0.01) and 24-hour postoperative Hb (7.7 g/dL, p < 0.001). Drain output between the transfusion and no transfusion groups varied significantly (p = 0.03), with transfusion patients having higher postoperative day 1 drain output of 362.6 mL and total drain output of 376.6 mL. In this series, postoperative drain use with concomitant weight-based IV TXA is shown to be safe and efficacious. We observed exceedingly low risk of postoperative transfusion compared with prior reports of drain use alone as well as preserved low rate of hemarthrosis that has previously been positively linked to drain use.

Pre-hospital tranexamic acid administration in patients with a severe hemorrhage: an evaluation after the implementation of tranexamic acid administration in the Dutch pre-hospital protocol.

PURPOSE: To evaluate the pre-hospital administration of tranexamic acid in ambulance-treated trauma patients with a severe hemorrhage after the implementation of tranexamic acid administration in the Dutch pre-hospital protocol. METHODS: All patients with a severe hemorrhage who were treated and conveyed by EMS professionals between January 2015, and December 2017, to any trauma-receiving emergency department in the eight participating trauma regions in the Netherlands, were included. A severe hemorrhage was defined as extracranial injury with > 20% body volume blood loss, an extremity amputation above the wrist or ankle, or a grade ≥ 4 visceral organ injury. The main outcome was to determine the proportion of patients with a severe hemorrhage who received pre-hospital treatment with tranexamic acid. A Generalized Linear Model (GLM) was performed to investigate the relationship between pre-hospital tranexamic acid treatment and 24 h mortality. RESULTS: A total of 477 patients had a severe hemorrhage, of whom 124 patients (26.0%) received tranexamic acid before arriving at the hospital. More than half (58.4%) of the untreated patients were suspected of a severe hemorrhage by EMS professionals. Patients treated with tranexamic acid had a significantly lower risk on 24 h mortality than untreated patients (OR 0.43 [95% CI 0.19-0.97]). CONCLUSION: Approximately a quarter of the patients with a severe hemorrhage received tranexamic acid before arriving at the hospital, while a severe hemorrhage was suspected in more than half of the non-treated patients. Severely hemorrhaging patients treated with tranexamic acid before arrival at the hospital had a lower risk to die within 24 h after injury.

Tranexamic acid is not associated with a higher rate of thrombotic-related reintervention after major vascular injury repair.

BACKGROUND: Tranexamic acid (TXA) is associated with lower mortality and transfusion requirements in trauma patients, but its role in thrombotic complications associated with vascular repairs remains unclear. We investigated whether TXA increases the risk of thrombosis-related technical failure (TRTF) in major vascular injuries (MVI). METHODS: The PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from 2013 to 2022 for MVI repaired with an open or endovascular intervention. The relationship between TXA administration and TRTF was examined. RESULTS: The TXA group (n = 297) had higher rates of hypotension at admission (33.6% vs. 11.5%, p < 0.001), need for continuous vasopressors (41.4% vs. 18.4%, p < 0.001), and packed red blood cell transfusion (3.2 vs. 2.0 units, p < 0.001) during the first 24 hours compared with the non-TXA group (n = 1941), although demographics, injury pattern, and interventions were similar. Cryoprecipitate (9.1% vs. 2%, p < 0.001), and anticoagulant administration during the intervention (32.7% vs. 43.8%, p < 0.001) were higher in the TXA group; there was no difference in the rate of factor VII use between groups (1% vs. 0.7%, p = 0.485). Thrombosis-related technical failure was not different between the groups (6.3% vs. 3.8 p = 0.141) while the rate of immediate need for reoperation (10.1% vs. 5.7%, p = 0.006) and overall reoperation (11.4% vs. 7%, p = 0.009) was significantly higher in the TXA group on univariate analysis. There was no significant association between TXA and a higher rate of immediate need for reintervention (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.75-1.88; p = 0.465), overall reoperation rate (OR, 1.33; 95% CI, 0.82-2.17; p = 0.249) and thrombotic events in a repaired vessel (OR, 1.07; 95% CI, 0.60-1.92; p = 0.806) after adjusting for type of injury, vasopressor infusions, blood product and anticoagulant administration, and hemodynamics. CONCLUSION: Tranexamic acid is not associated with a higher risk of thrombosis-related technical failure in traumatic injuries requiring major vascular repairs. Further prospective studies to examine dose-dependent or time-dependent associations between TXA and thrombotic events in MVIs are needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

The association of thromboembolic complications and the use of tranexamic acid during resection of intracranial meningiomas: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Antifibrinolytics, such as tranexamic acid (TXA), have been shown to decrease intraoperative blood loss across multiple surgical disciplines. However, they carry the theoretical risk of thromboembolic events secondary to induced hypercoagulability. Therefore, the aim of this study was to systematically review the available literature and perform a meta-analysis on the use of TXA in meningioma resection to assess thromboembolic risks. METHODS: The PubMed, Web of Science, and Google Scholar databases were reviewed for all randomized controlled trials presenting primary data on TXA use during resection of intracranial meningiomas. Data were gathered on operative duration, venous thromboembolic complications, deep venous thrombosis, use of allogeneic blood transfusion, estimated blood loss (EBL), and postoperative hemoglobin. Patients who received TXA were compared with controls who did not receive TXA intraoperatively using random-effects models. RESULTS: A total of 508 unique articles were identified, of which 493 underwent full-text review. Ultimately, 6 studies with 381 total patients (190 receiving TXA) were included in the final analysis. All 6 trials were randomized, blinded, and placebo controlled with a TXA administration rate of a 20-mg/kg load followed by a 1-mg/kg/hr infusion. All studies were performed in lower-middle-income countries. There were no reported instances of venous thromboembolism (VTE) in the TXA and non-TXA cohorts. Patients receiving TXA exhibited fewer allogeneic transfusions (21.5% vs 41.6% [OR 0.26, 95% CI 0.09-0.77], p = 0.02) and lower EBL (MD -282.48 mL [95% CI -367.77 to -197.20 mL], p < 0.001) compared with patients who did not receive TXA, and they also had lower rates of perioperative complications (10.7% vs 19.9% [OR 0.47, 95% CI 0.2-0.95], p = 0.04). CONCLUSIONS: Current literature suggests that TXA is not associated with increased risk for VTE when administered during resection of intracranial meningioma. TXA appears to decrease intraoperative blood loss and allogeneic transfusion requirements during meningioma resection and thus may improve the safety of surgical management of this pathology.

Intravenous Tranexamic Acid Significantly Improved Visualization and Shortened the Operation Time in Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis of Level I and II Studies.

PURPOSE: To further clarify the role of tranexamic acid (TXA) in arthroscopic rotator cuff repair (ARCR), especially visual field clarity and operation time. METHODS: We searched the PubMed, Cochrane Library, and Embase databases to find prospective randomized controlled clinical trials (RCTs) examining the use of TXA in ARCR. All included RCTs were evaluated for methodological quality using the Cochrane Collaboration's risk of bias tool. We used Review Manager 5.3 for meta-analysis and calculated the weighted mean difference (WMD) and 95% confidence interval (CI) of the related outcome indicators. The GRADE system was used to evaluate the strength of the clinical evidence provided by the included studies. RESULTS: Six RCTs (3 Level I, 3 Level II) from four countries or regions were included in this study: 2 studies used intra-articular (IA) TXA, and 4 studies used intravenous TXA. A total of 451 patients underwent ARCR, including 227 patients in the TXA group and 224 patients in the non-TXA group. In 2 RCTs evaluating good visualization, intravenous TXA achieved a better surgical field of view in ARCR compared to the control group (P =.036; P = .045). Meta-analysis showed that compared with non-TXA, intravenous TXA shortened the operation time (WMD = -12.87 min, 95% CI: -18.81 to -6.93). These two RCTs did not reveal a statistically significant difference in the impact of intravenous TXA and non-TXA on mean arterial pressure (MAP) (P = .306; P = .549). Compared with epinephrine (EPN), IA TXA had no significant effects on improving the visual field clarity under arthroscopy, shortening the operation time or reducing the total amount of irrigation fluid (P > .05). Compared with saline irrigation, IA TXA improved the surgical field of vision and shortened the operation time (P < .001). No adverse events were reported for either intravenous TXA or IA TXA. CONCLUSIONS: Intravenous TXA can shorten the operation time of ARCR, and the conclusions of existing RCTs suggest that intravenous TXA can improve visual field clarity during ARCR, thus supporting the application of intravenous TXA in ARCR. Compared with EPN, IA TXA was not better at improving the visual field clarity under arthroscopy and shortening the operation time, but it was better than saline irrigation. LEVEL OF EVIDENCE: Level II, systematic review and meta-analysis of Level I and II studies.

Intravenous Application of Tranexamic Acid in Patients Undergoing Plastic Surgery: A Systematic Review and Meta-analysis with GRADE Quality Assessment.

BACKGROUND: Tranexamic acid (TXA) is a versatile antifibrinolytic agent that is widely used in modern surgeries. This review assessed the safety and efficacy of intravenous (IV) TXA in plastic surgery versus controls. METHODS: This review selected English-language Randomized controlled trials (RCTs) evaluating IV TXA effects in plastic surgery from four electronic databases, PubMed, Web of Science, Embase, and Cochrane Library up to April 9, 2023. Primary outcomes were blood loss volume (BLV) and transfusion occurrence, with operation time and surgical field assessment as secondary outcomes. IV TXA-related complications were also important indicators. Meta-analyses and qualitative analyses were conducted and the quality of the evidence was assessed. RESULTS: Thirty RCTs with 2150 patients were included. The total standard mean difference (SMD) of BLV and pooled relative risk of transfusion occurrence between the IV TXA and the control groups were - 1.11 (95% CI, - 1.42 to - 0.80) and 0.36 (95% CI, 0.23 to 0.55) respectively, indicating a significant blood loss reduction with IV TXA treatment, while an ambiguous outcome of operation time was observed, with an SMD of - 0.22 (95% CI, - 0.42 to - 0.02). The quality of evidence for BLV and transfusion occurrence was low and medium, respectively. A quantitative analysis of surgical field assessment was not performed because of the substantial heterogeneity in scoring methods. No IV TXA-related complications were observed. CONCLUSIONS: In plastic surgery, IV TXA administration results in less blood loss, reduced need for transfusion and better surgical fields but probably does not increase the risk of adverse events. LEVEL OF EVIDENCE I: 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 Table of Contents or online Instructions to Authors www.springer.com/00266 .

A comparative analysis of tranexamic acid dosing strategies in traumatic major hemorrhage.

INTRODUCTION: Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus, or bolus plus infusion. The aim of this study was to determine the effect of different TXA dosing strategies on clinical outcomes in bleeding trauma patients. METHODS: Secondary analysis of a perpetual cohort study from a UK Level I trauma center. Adult patients who activated the local major hemorrhage protocol and received TXA were included. The primary outcome was 28-day mortality. Secondary outcomes were 24-hour mortality, multiple organ dysfunction syndrome, venous thromboembolism, and rotational thromboelastometry fibrinolysis. RESULTS: Over an 11-year period, 525 patients were included. Three dosing groups were identified: 1 g bolus only (n = 317), 1 g bolus +1 g infusion over 8 hours (n = 80), and 2 g bolus (n = 128). Demographics and admission physiology were similar, but there were differences in injury severity (median Injury Severity Score, 25, 29, and 25); and admission systolic blood pressure (median Systolic Blood Pressure, 99, 108, 99 mm Hg) across the 1-g, 1 g + 1 g, and 2-g groups. 28-day mortality was 21% in each treatment group. The incidence of multiple organ dysfunction syndrome was significantly higher in the bolus plus infusion group (84%) vs. 1 g bolus (64%) and 2 g bolus (62%) group, p = 0.002, but on multivariable analysis was nonsignificant. Venous thromboembolism rates were similar in the 1-g bolus (4%), 2 g bolus (8%) and bolus plus infusion groups (7%). There was no difference in rotational thromboelastometry maximum lysis at 24 hours: 5% in both the 1-g and 2-g bolus groups vs. 4% in bolus plus infusion group. CONCLUSION: Clinical outcomes and 24-hour fibrinolysis state were equivalent across three different dosing strategies of TXA. Single bolus administration is likely preferable to a bolus plus infusion regimen. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.