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The Optimal Dose, Efficacy and Safety of Tranexamic Acid and Epsilon-Aminocaproic Acid to Reduce Bleeding in TKA: A Systematic Review and Bayesian Network Meta-analysis
Zheng C, Ma J, Xu J, Li M, Wu L, Wu Y, Liu Y, Shen B
Orthopaedic surgery. 2023
Abstract
OBJECTIVE The optimal dose and efficacy of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in total knee arthroplasty (TKA) were under controversial, and we aimed to make comparisons between different doses of TXA and EACA in intravenous (IV) or intra-articular (IA) applications in patients undergoing TKA. METHODS This network meta-analysis was guided by the Priority Reporting Initiative for Systematic Assessment and Meta-Analysis (PRISMA). According to the administrations of antifibrinolytic agents, patients in eligible studies were divided into three subgroups: (i) IA applications of TXA and EACA; (ii) IV applications (g) of TXA and EACA; (iii) IV applications (mg/kg) of TXA and EACA. Total blood loss (TBL), hemoglobin (HB) drops and transfusion rates were the primary outcomes, while drainage volume, pulmonary embolism (PE) or deep vein thrombosis (DVT) risk were the secondary outcomes. A multivariate Bayesian random-effects model was adopted in the network analysis. RESULTS A total of 38 eligible trials with different regimens were assessed. Overall inconsistency and heterogeneity were acceptable. Taking all primary outcomes into account, 1.0-3.0 g TXA were most effective in IA applications, 1-6 g TXA and 10-14 g EACA were most effective in IV applications (g), while 30 mg/kg TXA and 150 mg/kg EACA were most effective in IV applications (mg/kg). None of the regimens showed increasing risk for pulmonary embolism (PE) or deep vein thrombosis (DVT) compared with placebo. CONCLUSION 0 g IA TXA, 1.0 g IV TXA or 10.0 g IV EACA, as well as 30 mg/kg IV TXA or 150 mg/kg IV EACA were most effective and enough to control bleeding for patients after TKA. TXA was at least 5 times more potent than EACA.
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Combination of Intravenous and Intra-Articular Application of Tranexamic Acid and Epsilon-Aminocaproic Acid in Primary Total Knee Arthroplasty: A Prospective Randomized Controlled Trial
Zheng C, Ma J, Xu J, Si H, Liu Y, Li M, Shen B
Orthopaedic surgery. 2022
Abstract
OBJECTIVE There were limited randomized controlled trials (RCTs) of epsilon-aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra-articular (IA) administration on reducing blood loss in patients following primary TKA. METHODS From January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n = 90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra-articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n = 91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra-articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi-square tests and Fisher's exact tests were utilized to compare categorical variables, while the independent-samples t-tests and Mann-Whitney tests were used to compare continuous variables. RESULTS The patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P = 0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P = 0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P = 0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81 day, which is longer than 2.62 ± 0.68 day in TXA group (P < 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P < 0.01). CONCLUSION Although the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.
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Early Tranexamic Acid in Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Jiao X, Li M, Li L, Hu X, Guo X, Lu Y
Frontiers in neurology. 2021;12:721125
Abstract
Objective: Intracranial hemorrhage (ICH) is a common complication of traumatic brain, in which tranexamic acid has been recommended as an additional therapy to prevent a second bleeding. However, the effect of early administration of tranexamic acid for ICH patients remains controversial. Methods: A systematic search was performed in Cochrane Library, Medline, Embase, and Web of Science. Poor outcome refers to significant hemorrhage growth, new intracranial hemorrhage, new focal cerebral ischaemic lesions, the need for neurosurgery, or death. Study heterogeneity and publication bias were estimated. Results: Seven randomized controlled trials involving 3,192 participants were included in our meta-analysis. Tranexamic acid administration in ICH patients was associated with better outcomes of hematoma expansion (odd ratios [OR] 0.79; 95% confidence interval (CI) CI, 0.67-0.93; I (2) = 0%; P = 0.006) and growth of hemorrhagic lesions (weighted mean difference [WMD], -1.97 ml; 95% CI, -2.94 to -1.00; I (2) = 14%; P < 0.001) than the placebo. No difference was found between the mortality, poor outcome, neurosurgical intervention, new bleeding, and the duration of hospital stay. Moreover, no publication bias was found. Conclusion: Our analysis reveals that the early treatment with tranexamic acid can significantly reduce the incidence of hematoma expansion and the volume of hemorrhagic lesion, but does not exert considerable effects on mortality, poor outcome, neurosurgery, rebleeding, and the duration of stay.
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Early intravenous tranexamic acid intervention reduces post-traumatic hidden blood loss in elderly patients with intertrochanteric fracture: a randomized controlled trial
Ma H, Wang H, Long X, Xu Z, Chen X, Li M, He T, Wang W, Liu L, Liu X
Journal of orthopaedic surgery and research. 2021;16(1):106
Abstract
PURPOSE Elderly patients with intertrochanteric fractures exhibit post-traumatic hidden blood loss (HBL). This study aimed to evaluate the efficacy and safety of reducing post-traumatic HBL via early intravenous (IV) tranexamic acid (TXA) intervention in elderly patients with intertrochanteric fracture. METHODS A prospective randomized controlled study was conducted with 125 patients (age ≥ 65 years, injury time ≤ 6 h) who presented with intertrochanteric fracture from September 2018 and September 2019. Patients in the TXA group (n = 63) received 1 g of IV TXA at admission, whereas those in the normal saline (NS) group (n = 62) received an equal volume of saline. Hemoglobin (Hgb) and hematocrit (Hct) were recorded at post-traumatic admission (PTA) and on post-traumatic days (PTDs) 1-3. HBL was calculated using the Gross formula. Lower extremity venous ultrasound was performed to detect venous thrombosis. RESULTS Hgb on PTDs 2 and 3 was statistically higher in the TXA group than in the NS group. Hct and HBL on PTDs 1-3 were significantly less in the TXA group compared to the NS group. Preoperative transfusion rate was significantly lower in the TXA group compared with the NS group. There was no difference between the two groups with regard to the rates of complications. CONCLUSION Early IV TXA intervention could reduce post-traumatic HBL and pre-operative transfusion rate in elderly patients with intertrochanteric fractures without increasing the risk of venous thrombosis.
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Efficacy and safety of perioperative tranexamic acid in elderly patients undergoing trochanteric fracture surgery: a randomised controlled trial
Chen F, Jiang Z, Li M, Zhu X
Hong Kong medical journal = Xianggang yi xue za zhi. 2019
Abstract
INTRODUCTION Trochanteric fractures result in a high frequency of considerable blood loss, a high incidence of blood transfusions, and a high risk of perioperative morbidity and mortality in elderly patients. This study aimed to evaluate the efficacy and safety of a three-dose regimen of tranexamic acid on blood loss and transfusion rate in elderly patients with trochanteric fractures. METHODS Eligible patients with trochanteric fractures surgically treated by dynamic hip screw and proximal anti-rotating intramedullary nail between March 2016 and October 2017 were enrolled in the study. Patients were randomly assigned to receive 15 mg/kg intravenous tranexamic acid dissolved in 100 mL of saline (TXA group) or 100 mL of saline solution (placebo group) over 10 minutes before, during, and after surgery. Perioperative blood loss, obvious blood loss, and hidden blood loss in the two groups were calculated separately. Vascular events and patient mortality over 6 months' follow-up were noted. RESULTS In total, 176 patients were included. Compared with the placebo group (n=88), patients in the TXA group (n=88) had less blood loss: perioperative blood loss was 205.5 mL (P<0.001), obvious blood loss was 125 mL (P<0.001), and hidden blood loss was 76.5 mL (P<0.001); reduced incidence of blood transfusion (17% vs 35%, P=0.007); and shorter hospital stays (median [interquartile range], 7 [6-8] vs 8.5 [7.5-9] days, P<0.001). CONCLUSION Tranexamic acid significantly lowered perioperative blood loss and blood transfusion rate without an increased risk of venous thromboembolism or mortality in elderly patients with trochanteric fractures treated with dynamic hip screw or proximal anti-rotating intramedullary nail.
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Blood loss and cost-effectiveness of oral vs intravenous tranexamic acid in primary total hip arthroplasty: A randomized clinical trial
Wu Y, Zeng Y, Hu Q, Li M, Bao X, Zhong J, Shen B
Thrombosis Research. 2018;171:143-148.
Abstract
BACKGROUND To assess the blood loss and cost-effectiveness of the oral and intravenous (IV) administration of tranexamic acid (TXA) for the treatment of primary total hip arthroplasty (THA). METHODS From January 2017 to August 2017, 100 patients undergoing primary THA were enrolled and randomly divided into two groups. In the oral TXA group (N=50), 1g of TXA (2 tablets of 500mg) was given 2h before the incision, and the same dose was repeated 3h and 6h postoperatively. In the IV TXA group (N=50), 1g of TXA was administered 10min before the incision, and the same dose was repeated 3h and 6h postoperatively. The total follow-up period was 6months. RESULTS There were no statistically significant differences in total blood loss (863.3+/-272.5mL and 886.1+/-200.2mL, P=0.66), maximum Hb drop (2.9+/-0.6g/dl and 3.1+/-0.8g/dl, P=0.17), maximum Hct drop (7.4+/-2.1% and 7.7+/-1.8%, P=0.48), transfusion rates (1 and 2, P=1.00) and transfusion units (1.5 u and 3 u, P=0.56) between the two groups. However, the costs of TXA in the oral group were significantly lower than those in the IV TXA group ( yen600 and yen3150, P<0.01). There was no difference in the Hb levels on postoperative days 1 and 3. No significant differences were found for operating time, hospital length of stay, DVT and/or PE, and wound complications in the postoperative follow-up. CONCLUSIONS The study demonstrated that the oral and IV administration of TXA in patients undergoing THA was proved to be an equivalent and effective method in reducing blood loss and transfusion rates. However, oral TXA is more cost-effectiveness than IV TXA, and it may be an alternative to the IV form.