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1.
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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2.
The optimal regimen, efficacy and safety of tranexamic acid and aminocaproic acid to reduce bleeding for patients after total hip arthroplasty: A systematic review and Bayesian network meta-analysis
Zheng C, Ma J, Xu J, Wu L, Wu Y, Liu Y, Shen B
Thrombosis research. 2022;221:120-129
Abstract
OBJECTIVES We aimed to evaluate the optimal regimen, efficacy and safety of tranexamic acid (TXA) and aminocaproic acid (EACA) for patients after total hip arthroplasty (THA). METHODS The network meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. The outcomes were total blood loss, transfusion rates, hemoglobin (HB) drop, and risk for pulmonary embolism (PE) or deep vein thrombosis (DVT). Subgroup analyses were performed among most effective regimens to determine the influences of timing and number of doses. RESULTS A total of 56 eligible RCTs with different regimens were assessed. For reducing total blood loss, all high doses of TXA and EACA except high dose of intra-articular (IA) TXA, as well as medium dose of combination of intravenous and intra-articular (combined IV/IA) TXA were most effective. All high doses of TXA, as well as medium dose of combined IV/IA TXA did not show inferiority in reducing transfusion rates and HB drop compared with other regimens. No regimens showed higher risk for PE or DVT compared with placebo, and no statistical differences were seen among most effective regimens in subgroup analyses. CONCLUSIONS As effective as high doses of EACA and TXA, medium dose (20-40 mg/kg or 1.5-3.0 g) of combined IV/IA TXA was enough to control bleeding for patients after THA without increasing risk for PE/DVT. TXA was at least 5 times more potent than EACA. Timing and number of doses had few influences on blood conserving efficacy. LEVEL OF EVIDENCE Level I.
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3.
The efficacy and safety of combined administration of intravenous and topical tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized controlled trials
Xiong H, Liu Y, Zeng Y, Wu Y, Shen B
Bmc Musculoskeletal Disorders. 2018;19((1)):321.
Abstract
BACKGROUND The combined administration of intravenous (IV) and topical tranexamic acid (TXA) in primary total knee (TKA) knee remains controversial. The purpose of this meta-analysis was to assess the efficacy and safety of combined administration of IV and topical TXA in primary TKA. METHODS PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Google Search Engine and China National Knowledge Infrastructure databases were searched for randomized controlled trials (RCTs) were comparing the combined administration of IV and topical TXA following primary TKA. The primary outcomes were total blood loss, maximum hemoglobin drop, and deep venous thrombosis (DVT) and/or pulmonary embolism (PE). The second outcomes were drainage volume and transfusion requirements. Data were analyzed using RevMan 5.3. RESULTS A total of 6 RCTs involving 701 patients were included in the meta-analysis. The combined group provided lower total blood loss (MD - 156.34 mL, 95% CI, - 241.51 to - 71.18; P = 0.0003), drainage volume (MD - 43.54 mL, 95% CI, - 67.59 to - 19.48; P = 0.0004), maximum hemoglobin drop (MD - 0.56 g/dl, 95% CI, - 0.93 to - 0.19; P = 0.003) than IV TXA alone. No significant difference were found in terms of transfusion requirements (RR 0.48, 95% CI, 0.16 to 1.44; P = 0.19), DVT (RR 1.01, 95% CI, 0.14 to 7.12; P = 0.99) and PE (RR 0.33, 95% CI, 0.01 to 7.91; P = 0.49) between the two group. Subgroup analyses shows that the combined group was less total blood loss in non-tourniquet (P = 0.0008), topical TXA dose > 1.5 g (P < 0.00001) and number of IV TXA ≥ 2 doses (P = 0.005) of TXA compared with the IV group alone. CONCLUSIONS The available evidence indicates combined group were associated with lower total blood loss, drainage volume, and maximum hemoglobin drop. A similar transfusion requirement was found in both groups. Subgroup analyses demonstrates that total blood loss was less in patients with non-tourniquet, topical TXA dose > 1.5 g and number of IV TXA ≥ 2 doses of TXA. There was no increase the rates of DVT and PE.
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4.
Effect of knee flexion position and combined application of tranexamic acid on blood loss following primary total knee arthroplasty: a prospective randomized controlled trial
Zeng Y, Si H, Li C, Wu Y, Shen B
International Orthopaedics. 2018;42((3):):529-535
Abstract
PURPOSE The aim of this study was to demonstrate the association between tranexamic acid (TXA)-combined application and knee flexion in the first 24 hour post-operatively that could reduce total blood loss and transfusion need in patients undergoing total knee arthroplasty (TKA), without sacrificing safety. METHODS Ninety TKA patients were divided into three groups randomly: the flexion group: the knee was in 90 degrees flexion position for the first 12 hour post-surgery and kept at 60 degrees for the next 12 hour, combined with 1 g TXA topical and 1 g TXA intravenous application. The extension group: the knee was in fully extension position post-operatively, combined with topical and intravenous TXA application. The controlled group: the knee was in fully extension position post-operatively combined with single intravenous TXA application. The primary outcomes included blood loss variables and transfusion values. The secondary outcomes included post-operative hospital stay, knee flexion degree, complication rate, and hospital charge. RESULTS The total blood loss and transfusion needs in the flexion group were significantly reduced in comparison with that in the extension group and controlled group. The post-operative knee flexion motion was significant higher in the flexion group than the other two groups. There was no difference among the three groups with regard to the rates of complications. CONCLUSIONS Keeping the knee in flexion position combined with topical and intravenous TXA application in patients undergoing primary unilateral TKA significantly reduced post-operative bleeding and the transfusion rate compared with what was found after treatment with extension knee position or single intravenous TXA application. LEVEL OF EVIDENCE Therapeutic Level I.
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5.
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.
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6.
Efficacy and safety of limb position on blood loss and range of motion after total knee arthroplasty without tourniquet: A randomized clinical trial
Wu Y, Lu X, Ma Y, Zeng Y, Xiong H, Bao X, Shen B
International Journal of Surgery (London, England). 2018;60:182-187.
Abstract
BACKGROUND The purpose of this study was to investigate the effect of postoperative limb position on blood loss and knee function after primary total knee arthroplasty without tourniquet. MATERIAL AND METHODS One hundred patients were randomly assigned into 2 groups: Group A was given a knee flexion position at 60 degrees for 24h after surgery but without the tourniquet use. Patients in group B was received the tourniquet use the same flexion position as the Group A. All patients received intravenous (IV) tranexamic acid (TXA) 15mg/kg before skin incision and another 1g of IV-TXA after 3h. RESULTS The total blood loss was similar in the 2 groups. Group A had significantly less hidden blood loss and drainage volume (P=0.023, P<0.001), and higher intraoperative blood loss than the Group B (P<0.001). The visual analog scale and knee circumference in Group A were lower than the Group B on postoperative days 1, 3 and 5. The range of motion was also lowering in Group A than the Group B on postoperative days 1, 3, 5 and at the 1 month. No significant differences (P>0.05) were observed between the 2 groups regarding maximum hemoglobin drop, transfusion rate, postoperative hospital stay, DVT and/or PE, and wound-related complications. CONCLUSION Based on the current evidence, patients treated with postoperative limb positions without a tourniquet can effectively reduce hidden blood loss and drainage volume, as well as better early clinical benefits than those treated with a tourniquet. LEVEL OF EVIDENCE Therapeutic Level I.
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7.
Application of tranexamic acid and diluted epinephrine in primary total hip arthroplasty
Wu Y, Zeng Y, Bao X, Xiong H, Fan X, Shen B
Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2018;29((5):):451-457.
Abstract
Tranexamic acid (TXA) and diluted epinephrine (DEP) has been reported to be an efficient and well tolerated way for reducing blood loss in total hip arthroplasty (THA). This meta-analysis was designed to compare the effectiveness of combination application of TXA with DEP in primary THA. The following electronic databases were searched, including PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure and Google Search Engine, for published studies involving the TXA with DEP in primary THA. All randomized controlled trials (RCTs) were included. Statistical analysis was assessed using RevMan 5.3 software. Five independent RCTs were included, with a total sample size of 496 patients. The application of TXA with DEP can significantly reduce total blood loss (mean difference, 246.13; 95% CI, -369.95 to -122.32; P < 0.0001), hidden blood loss (mean difference, 299.98; 95% CI -433.61 to -166.35; P < 0.0001) and transfusion requirements (risk ratio, 0.50; 95% CI 0.28-0.90; P = 0.02) compared with the TXA alone. There were no significant differences in intraoperative blood loss (P = 0.46), drainage volume (P = 0.61), length of stay (P = 0.53) and the rate of DVT (P = 0.56) between the two groups. On the basis of current evidence, this meta-analysis showed that the application TXA with DEP is a well tolerated and efficacious treatment to reduce total blood loss, hidden blood loss and transfusion requirements in primary THA, without increasing the risk of DVT in primary THA.
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8.
Clamping drainage is unnecessary after minimally invasive total knee arthroplasty in patients with tranexamic acid: A randomized, controlled trial
Wu Y, Yang T, Zeng Y, Li C, Shen B, Pei F
Medicine. 2017;96((7)):e5804.
Abstract
BACKGROUND Drainage and tranexamic acid (TXA) have been widely used in total knee arthroplasty (TKA). However, it remains unclear whether it is necessary to clamp the drain after minimally invasive TKA (MIS-TKA) when TXA is used. We therefore conducted a randomized controlled trial to compare the effects of clamping versus not clamping drainage following MIS-TKA in patients in whom TXA was used. METHODS From January 2015 to December 2015, 121 patients undergoing unilateral primary MIS-TKA were enrolled and randomly divided into 2 groups. In the clamping group (N = 60), drainage was clamped for the 1st 4 postoperative hours. In the nonclamping group (N = 61), drainage was not clamped. All patients underwent a minimidvastus approach and received 10 mg/kg TXA intravenously before tourniquet deflation. We recorded the total blood loss, drainage volume, and transfusion requirements in the postoperative period. We also measured the hemoglobin (Hb) and hematocrit (Hct) levels on postoperative days 1, 3, and 5. Other factors, including range of motion (ROM), visual analog scale (VAS), and occurrence of wound-related complications, deep vein thrombosis (DVT), and pulmonary embolism (PE) were recorded at the time of discharge and 1 and 6 months postoperatively. No statistically significant differences were found between the 2 groups with regard to age, gender, weight, BMI, preoperative Hb and Hct levels, preoperative ROM, VAS, duration of surgery, anesthesia method, and the American Society of Anesthesiologists classification. RESULTS The clamping group experienced better drainage volume results than the nonclamping group (P < 0.001). There were no statistically significant differences in TBL and transfusion requirements (P = 0.105 and 0.276, respectively); Hb and Hct levels on postoperative days 1, 3, and 5 were similar between the 2 groups. No significant differences were found for ROM, VAS, DVT, PE, wound-related complications, and hospital length of stay in the postoperative follow-up. CONCLUSION Based on our findings, clamping drainage is unnecessary after routine MIS-TKA using TXA.
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9.
Tranexamic acid reduces blood loss and transfusion requirements in primary simultaneous bilateral total knee arthroplasty: a meta-analysis of randomized controlled trials
Wu Y, Yang T, Zeng Y, Si H, Li C, Shen B
Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2017;28((7):):501-508
Abstract
: The aim of this meta-analysis is to assess the effectiveness and safety of intravenous application tranexamic acid (TXA) in primary simultaneous bilateral total knee arthroplasty (TKA). We searched electronic databases including PubMed, Embase, the Web of Science, the Cochrane Library and the Google Scholar, for published studies involving the intravenous application TXA in primary simultaneous bilateral TKA. All randomized controlled trials were included. The focus of the meta-analysis was on the outcomes of total blood loss, drainage volume, transfusion requirements and deep venous thrombosis (DVT) and/or pulmonary embolism. The relevant data were analyzed using RevMan 5.2. Six high randomized controlled trials were included, with a total sample size of 394 patients. The intravenous application of TXA significantly reduced total blood loss [95% confidence interval (CI), -519.52 to -126.40; P = 0.001], drainage volume (95% CI, -551.76 to -138.57; P = 0.001) and transfusion requirements (risk ratio, 0.38; 95% CI, 0.21-0.68; P = 0.001) compared with the control group. In addition, there were no significant differences in the rate of DVT (P = 1.00) and/or pulmonary embolism between the two groups. Based on the current evidence, this meta-analysis showed that intravenous application of TXA is effective and a well tolerated treatment to reduce total blood loss, drainage volume and transfusion requirements without increasing the risk of DVT and/or pulmonary embolism in primary simultaneous bilateral TKA.
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10.
A systematic review and meta-analysis of the use of antifibrinolytic agents in total hip arthroplasty
Huang F, Wu Y, Yin Z, Ma G, Chang J
Hip International. 2015;25((6)):502-9.
Abstract
BACKGROUND Antifibrinolytic agents such as tranexamic acid (TXA), epsilon aminocaproic acid (EACA), and aprotinin are widely used to reduce bleeding and the need for transfusion in cardiac, orthopaedic, and hepatic surgery. We aimed to assess the efficacy and safety of antifibrinolytic agents in total hip arthroplasty (THA). METHODS A systematic literature search was performed using MEDLINE, PubMed, EMBASE, and Cochrane databases, as well as the reference lists of relevant articles. Only randomised controlled trials were eligible for this study. The weighted mean difference in blood loss, number of transfusions per patient, and the summary risk ratio of transfusion requirements and deep-vein thrombosis (DVT) were calculated in the antifibrinolytic agents-treated and control groups. RESULTS A total of 28 randomised controlled trials involving 2,131 patients were included. Patients receiving antifibrinolytic agents had a reduced total blood loss by a mean of 389.14 ml (95% CI, -483.05 to -295.23), and the number of blood transfusions per patient by 0.65 units (95% CI, -1.19 to -0.12). Antifibrinolytic agents led to a significant reduction in transfusion requirements (RR 0.55; 95% CI, 0.43 to 0.70) and no increase in the risk of DVT (RR 0.85; 95% CI, 0.51 to 1.42). CONCLUSIONS Our meta-analysis demonstrated that antifibrinolytic agents significantly reduce blood loss and blood transfusion requirements while not increasing the risk of DVT in patients undergoing total hip arthroplasty.