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.

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.

The effect of preoperative use of anticoagulants on the hemostatic effect of intravenous application of tranexamic acid in PLIF: a case control study.

Intravenous application of tranexamic acid (TXA) in posterior lumbar interbody fusion (PLIF) can effectively reduce blood loss without affecting coagulation function. However, it has not been reported whether preoperative use of anticoagulants may affect the efficacy of TXA in PLIF. The purpose of this study is to observe the effect of preoperative use of anticoagulants on coagulation indicators and blood loss after PLIF receiving intravenous unit dose TXA. A retrospective analysis was conducted on data from 53 patients with PLIF between 2020.11 and 2022.9, who received intravenous application of a unit dose of TXA (1 g/100 mL) 15 min before the skin incision after general anesthesia. Those who used anticoagulants within one week before surgery were recorded as the observation group, while those who did not use anticoagulants were recorded as the control group. The main observation indicators include surgical time, intraoperative blood loss, postoperative drainage volume, blood transfusion, and red blood cell (RBC), hemoglobin (HB), and hematocrit (HCT) measured on the 1st, 4th, 7th, and last-test postoperative days. Secondary observation indicators included postoperative incision healing, deep vein thrombosis of lower limbs, postoperative hospital stay, and activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), and platelets (PLT) on the 1st and 4th days after surgery. The operation was successfully completed in both groups, the incision healed well after operation, and no lower limb deep vein thrombosis occurred. There was no significant difference in surgical time, intraoperative blood loss, postoperative drainage volume, and blood transfusion between the two groups (p > 0.05). There was no significant difference in the RBC, HB, and HCT measured on the 1st, 4th, 7th, and last-test postoperative days between the two groups (p > 0.05). There was no statistically significant difference in APTT, PT, TT, FIB and PLT between the two groups on the 1st and 4th postoperative days (p > 0.05). There was no significant difference in postoperative hospital stay between the two groups (p > 0.05). The use of anticoagulants within one week before surgery does not affect the hemostatic effect of intravenous unit dose TXA in PLIF.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Efficacy and safety of intravenous tranexamic acid in microscopic modified radical mastoidectomy: a study protocol for a prospective, randomised, double-blind controlled trial.

INTRODUCTION: Radical mastoidectomy is a common procedure for chronic suppurative otitis media, typically performed under a microscope. The smooth operation is closely related to the clarity of the operative field. Our trial is designed to investigate whether the intravenous administration of tranexamic acid (TXA) can improve the clarity of the operative field, reduce the operative time, and increase surgeon satisfaction. METHODS AND ANALYSIS: This study is a prospective, randomised, double-blinded, controlled trial that aims to investigate the effects of TXA on patients with otitis media. The trial will include patients between the ages of 18 and 65 who will be randomly assigned to either the TXA group or the control group. In the TXA group, patients will receive 1 g of TXA diluted to 20 mL of normal saline before anaesthesia induction while the control group will receive 20 mL of normal saline. The primary outcome measure will be the Modena Bleeding Score, which will assess the clarity of the surgical field. Secondary outcomes will include the surgeon's satisfaction with surgical conditions, operation time, laboratory measurements (prothrombin time, activated partial thromboplastin time, fibrin degradation products, D-dimer) and levels of inflammatory factors (such as IL-6) at 24 hours postoperatively. In addition, the incidence of general adverse reactions such as postoperative nausea, vomiting and dizziness; serious adverse events such as arterial and venous thromboembolism, myocardial infarction and epilepsy within 90 days will be compared between the two groups. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee of Peking University People's Hospital (2021PHB173-001), on 19 July 2021. The trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100049183.

Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.

Effect of Intense Pulsed Light versus Intradermal Tranexamic Acid for the Management of Melasma.

OBJECTIVE: To compare the effectiveness of intense pulsed light (IPL) and intradermal tranexamic acid (TXA) in treating melasma. STUDY DESIGN: A cross-sectional analytical study. Place and Duration of the Study: Department of Dermatology, Dow International Medical College, Dow University Hospital, Karachi, Pakistan, from 15th January to 15th July 2023. METHODOLOGY: A total of 62 patients with melasma, aged 20-50 years, were divided into two groups. Group A (32 patients) received IPL (560 nm filter was used) treatment, and Group B (30 patients) received intradermal TXA. Each group underwent four treatment sessions with varying intervals. Melasma area and severity index (MASI) scores were used to compare the effects of treatment. RESULTS: After a 3-month treatment period, both groups showed reduced mMASI scores compared to baseline with a significant initial difference between Group A (8.6 ± 4.2) and Group B (5.4 ± 2.7, p <0.001). However, post-treatment, there was no significant difference in mMASI scores (Group A: 3.8 ± 2.6; Group B: 3.2 ± 2.0, p = 0.29). IPL treatment (Group A) demonstrated a significant reduction in mMASI scores (57.1 ± 19.7) compared to intradermal TXA treatment (Group B, 42.2 ± 18.8, p = 0.0034). CONCLUSION: Both IPL and intradermal TXA treatments effectively reduced melasma, with IPL exhibiting superior results. However, post-treatment outcomes converged, emphasising the need for personalised approaches considering the unique characteristics of South East Asian skin. KEY WORDS: Intense pulsed light, Melasma, Intradermal tranexamic acid.

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.

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.

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.

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.

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 placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial.

BACKGROUND: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. METHODS: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. FINDINGS: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). INTERPRETATION: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. FUNDING: Australian Government Medical Research Future Fund.

The Statistical Fragility of Tranexamic Acid Use in the Orthopaedic Surgery Literature: A Systematic Review of Randomized Controlled Trials.

INTRODUCTION: Randomized controlled trials (RCTs) represent the highest level of evidence in orthopaedic surgery literature, although the robustness of statistical findings in these trials may be unreliable. We used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate the statistical stability of outcomes reported in RCTs that assess the use of tranexamic acid (TXA) across orthopaedic subspecialties. METHODS: PubMed, EMBASE, and MEDLINE were queried for RCTs (2010-present) reporting dichotomous outcomes with study groups stratified by TXA administration. The FI and rFI were defined as the number of outcome event reversals needed to alter the significance level of significant and nonsignificant outcomes, respectively. FQ was determined by dividing the FI or rFI by sample size. Subgroup analyses were conducted based on orthopaedic subspecialty. RESULTS: Six hundred five RCTs were screened with 108 studies included for analysis comprising 192 total outcomes. The median FI of the 192 outcomes was 4 (IQR 2 to 5) with an associated FQ of 0.03 (IQR 0.019 to 0.050). 45 outcomes were reported as statistically significant with a median FI of 1 (IQR 1 to 5) and associated FQ of 0.02 (IQR 0.011 to 0.034). 147 outcomes were reported as nonsignificant with a median rFI of 4 (IQR 3 to 5) and associated FQ of 0.04 (IQR 0.023 to 0.051). The adult reconstruction, trauma, and spine subspecialties had a median FI of 4. Sports had a median FI of 3. Shoulder and elbow and foot and ankle had median FIs of 6. DISCUSSION: Statistical outcomes reported in RCTs on the use of TXA in orthopaedic surgery are fragile. Reversal of a few outcomes is sufficient to alter statistical significance. We recommend reporting FI, rFI, and FQ metrics to aid in interpreting the outcomes reported in comparative trials.

[Case series of hereditary angioedema patients and use of tranexamic acid treatments in prophylaxis and acute crisis, experience in Perú]. / Serie de casos de pacientes con angioedema hereditario y uso de ácido tranexámico como tratamiento profiláctico, y en crisis agudas: experiencia en Perú.

BACKGROUND: Hereditary Angioedema (HAE) is a rare disease characterized by episodes of swelling, HAE crisis could cause death by suffocation, and also affect the quality of life in these patients. There exists an important disparity of HAE specific treatments between countries, inclusive in the same region, currently in Perú we use moderate and high doses of Tranexamic Acid (TA) in prophylaxis therapy and in acute HAE crisis respectively. OBJECTIVE: To report our experience with TA in three types of HAE patients and be a guide to other countries with this therapy, where HAE specific treatments are not registered. CASE REPORT: Patient 1: Woman. 49 years old. HAE-1. Symptoms began at the age of 12. Her final diagnosis was at age 45. Usually presents an acute crisis every two months approximately, she receives 2 g IV of TA when lips, tongue, facial episodes is beginning, eventually she needed other 1 - 2 g IV (after 4 hours). She receives Long-Term Prophylaxis (LTP) with TA (500 - 750 mg)/12 h. Patient 2: Woman 47 years old, HAE nC1INH-FXII. Symptoms began at the age of 19, during her first pregnancy, her definitive diagnosis was at the age of 41 years. She maintains a prophylaxis treatment of TA (750 mg-1,5 g)/daily; upper airway attacks are treated immediately with TA doses (1 - 2 g) when the crisis is beginning. Patient 3: Woman 43 years old, HAE-nC1INH-U. Genetic study did not recognize SERPING1, PLG1, ANGPT1, KNG1, FXII, mutations. Symptoms began at age 4, and her final diagnosis was at age 36. When the attack is beginning, she immediately receives TA (500 - 750 mg) orally / 12 hours during 2 to 3 days with acceptable tolerance and control of the HAE episodes. While the patients receive TA prophylaxis treatment doses (500 - 750 mg) every 8 or 12 hours respectively, the HAE episodes are less symptomatic and resolve in a few days. CONCLUSIONS: We found this systematic review, used TA orally, on-demand and prophylaxis therapy, maximum cumulative dose 3 g/24 h1. In our HAE patients, we used TA up to 4 g (2 g - 2 g) intravenous for control of acute crisis in a interval of 4 hours, when decreases the reaction, the orally maintenance dose should be prescribed, 1 g/8 h with a progressive decrease of the dose in the next days. Tranexamic Acid treatment was useful in our different types of HAE patients. Most of our patients use high doses of TA to slow down and stop slowly the HAE crisis. TA is probably an option in countries where specific treatments are not registered, it could be administered orally and/or intravenous. High doses of TA were well tolerated and with acceptable response in HAE attacks.

ANTECEDENTES: El Angioedema Hereditario (AEH) se caracteriza por episodios de hinchazón a niveles cutáneo y submucoso, una crisis podría causar muerte por asfixia. Además, afecta la calidad de vida de las personas que la padecen. Existe una disparidad importante de medicamentos específicos para el AEH entre países, inclusive en nuestra misma región. En Perú donde no son viables estos tratamientos, se utiliza el Ácido Tranexámico (AT) para las Profilaxis de Largo y Corto Plazo (PLP / PCP), y para las crisis agudas de AEH. OBJETIVO: Reportar la experiencia con el tratamiento de AT en tres tipos de pacientes con AEH, para que pueda ser usada como referencia en otros países en los que aún no se cuenta con medicamentos específicos para la enfermedad. REPORTE DE CASO: Paciente 1: Mujer de 49 años, AEH Tipo 1. Inició síntomas a los 12 años de edad. Diagnóstico definitivo a los 45 años. Actualmente, presenta crisis cada dos meses. Se le administran dosis de 2 g por IV de AT, cuando empieza crisis en cara, lengua y labios. Eventualmente ha necesitado entre 1 y 2 g por IV (después de cuatro horas), ella recibe PLP con AT (500 ­ 750 mg) cada 12 horas. Paciente 2: Mujer de 47 años, AEH-nC1INH-FXII. Inició síntomas a los 19 años durante su primer embarazo. Diagnóstico definitivo a los 41 años. Ella mantiene PLP con AT (750 mg ­ 1,5 g) diariamente. Los ataques de vía respiratoria alta son tratados inmediatamente con AT cuando la crisis inicia, con dosis de 1 a 2 g por IV. Paciente 3: Mujer de 43 años, AEH-nC1INH-D. Estudio genético no detecta mutación en SERPING1, PLG1, ANGPT1, KNG1 y FXII. Inició síntomas a los 4 años. Diagnóstico definitivo a los 36 años. Al iniciar las crisis, se administra AT por VO, entre 500 a 750 mg/12 horas durante dos o tres días con aceptable respuesta y tolerancia a los episodios de AEH. Mientras las pacientes reciban dosis de mantenimiento de AT, entre 500 y 750 mg cada 8 o 12 horas, las crisis suelen ser de menor intensidad y se resuelven en menos días. CONCLUSIONES: En esta revisión sistemática, utilizaron AT vía oral, a demanda y en tratamiento profiláctico, dosis máxima acumulada 3 g/24 h1. En nuestros pacientes con AEH, hemos utilizado AT hasta 4 g vía intravenosa en un intervalo de cuatro horas (2 g - 2 g); para el control de crisis agudas, cuando la reacción está cediendo, prescribimos la dosis de mantenimiento, 1 g/8 h con disminución progresiva de la dosis en los días siguientes. El tratamiento con ácido tranexámico ha sido de utilidad en nuestros pacientes con los distintos tipos de AEH. La mayoría de ellos utilizan altas dosis de AT para disminuir lentamente las crisis agudas de AEH. Se puede administrar vía oral o intravenosa. Es un medicamento que puede ser de ayuda en países donde no se tiene registro de tratamientos específicos para la enfermedad. Las dosis de AT han sido bien toleradas y con una respuesta aceptable en las crisis de estos pacientes con AEH.