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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.
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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3.
Local administration of epsilon-aminocaproic acid reduces post-operative blood loss from surgery for closed, Sanders III-IV calcaneal fractures
Zhong L, Xu Y, Wang Y, Liu Y, Huang Q
International orthopaedics. 2022
Abstract
PURPOSE To investigate whether local administration of epsilon-aminocaproic acid (EACA) is effective and safe in reducing the post-operative blood loss in surgery for Sanders III-IV calcaneal fractures. METHODS Patients with Sanders III-IV calcaneal fractures who were hospitalized in our hospital from January 2016 to February 2021 and underwent open reduction internal fixation (ORIF) via lateral approach with an L-shaped incision were included in the current study. Eighty five patients were randomly divided into two groups, EACA group (43) and control group (42). Twenty milliliters of 5% EACA solution or normal saline was perfused into the incision of patients in EACA group and control group, respectively. The volume of post-operative drainage was investigated as the primary outcome. Post-operative blood test, coagulation test, and wound complications were analyzed as the secondary outcomes. RESULTS The volume of post-operative drainage at 24 and 48 h was 164.8 ± 51.4 ml, 18.9 ± 3.8 ml for patients in EACA group, and 373.0 ± 88.1 ml, 21.2 ± 4.4 ml for patients in the control group, respectively. EACA greatly reduced the post-operative blood loss compared to the control (normal saline). The difference between the two groups was statistically significant. No statistically significant difference was found between EACA group and control group with regard to the pre-operative, baseline characteristics. Post-operative blood test results demonstrated that haemoglobin and hematocrit were significantly higher in EACA compared to those of control group. No significant difference was found between EACA group and control group in terms of the platelet counts, prothrombin time (P.T.), activated partial prothrombin time (APTT), and wound complications. CONCLUSION Local administration of EACA is effective in post-operative blood loss reduction in ORIF surgeries for Sanders III-IV types of calcaneal fractures without increasing the incidence of periwound complication.
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4.
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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5.
Efficacy and incidence of treatment related adverse events of thrombopoietin receptor agonists in adults with immune thrombocytopenia: a systematic review and network meta-analysis of randomized controlled study
Liu Y, Zhang HX, Su J, Geng QC, Lin X, Feng CX
Acta haematologica. 2022
Abstract
INTRODUCTION To conduct a network meta-analysis to assess the efficacy and incidence of treatment related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO) and hetrombopag for adult immune thrombocytopenia (ITP). METHODS Randomized controlled trails (RCTs) of the five therapies from inception to June 1, 2022 were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 x 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were caculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome. RESULTS In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI, 1.74-31.69) and rhTPO (OR, 3.86; 95%CI, 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0. CONCLUSIONS These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy of adult ITP.
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6.
Peri-Articular Injection of Tranexamic Acid Reduce Blood Loss and Transfusion Requirement During Total Knee Arthroplasty: A Meta-analysis
Liu Y, Shan D, Tian P, Li ZJ, Xu GJ, Fu X
Geriatric orthopaedic surgery & rehabilitation. 2022;13:21514593221101264
Abstract
BACKGROUND The aim of this meta-analysis was to evaluate the efficacy and safety of peri-articular injection of tranexamic acid (TXA) during total knee arthroplasty (TKA) from clinical controlled trials. METHOD Eligible scientific articles published prior to October 2021 were retrieved from the PubMed, Springer, ScienceDirect and Cochrane Library databases. The statistical analysis was performed with RevMan 5.1. RESULT 2 RCTs and 3 non-RCTs met the inclusion criteria. Meta-analysis showed significant differences in terms of hemoglobin reduction (MD = -1.04, 95% CI: -1.33 to -.76, P < .00001), total blood loss (MD = -342.80.70, 95% CI: -437.52 to -248.08, P < .00001), drainage volume (MD = -297.24, 95% CI: -497.26 to -97.23, P = .004) and blood transfusion rate (OR = .30, 95% CI: .14 to .62, P = .001) were found in the control group. No postoperative infection and deep venous thrombosis were found between 2 groups. CONCLUSION Peri-articular injection of TXA can effectively decrease perioperative blood loss and blood transfusion rate without increasing the incidence of postoperative complications during TKA.
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7.
The efficacy and safety of roxadustat treatment for anemia in patients with kidney disease: a meta-analysis and systematic review
Qie S, Jiao N, Duan K, Li J, Liu Y, Liu G
International urology and nephrology. 2021
Abstract
BACKGROUND Anemia is a common complication for patients with kidney disease. Roxadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), which is a newly approved oral drug for anemia. We performed this study to build evidence regarding efficacy and safety of roxadustat in kidney disease patients with or without dialysis. METHODS We searched the databases of PubMed, Embase, Cochrane library and clinicaltrials.gov from the inception to July 20, 2020. The randomized controlled trials (RCTs) which compared roxadustat with placebo or other therapies in the treatment of anemia in kidney disease patients were included. Data were extracted from eligible studies and pooled in a meta-analysis model using RevMan5.3 and stata13.0 software. RESULTS Eight RCTs with 1010 patients were included in our analysis. We found that roxadustat significantly increased hemoglobin (Hb) level (1.10 g/dL, 95% CI [0.52 g/dL, 1.67 g/dL], p = 0.0002), total iron-binding capacity (TIBC) (58.71 µg/dL, 95% CI [44.10 µg/dL, 73.32 µg/dL], p < 0.00001), iron level (9.28 µg/dL, 95% CI [0.11 µg/dL, 18.45 µg/dL], p = 0.05) compared with control group in kidney disease patients. In addition, our result showed that a significant reduction in hepcidin level (- 31.96 ng/mL, 95% CI [- 35.05 ng/mL, - 28.87 ng/mL], p < 0.00001), ferritin (- 44.82 ng/mL, 95% CI [- 64.42 ng/mL, - 25.23 ng/mL], p < 0.00001) was associated with roxadustat. No difference was found between roxadustat and control group in terms of oral iron supplementation, adverse events (AEs), serious adverse events (SAEs), infection, myocardial infraction, stroke, heart failure and death. CONCLUSIONS Roxadustat has higher mean Hb level than placebo or EPO. Due to the short follow-up period and the lack of critical data, more RCTs are needed to prove long-term safety and effectiveness of roxadustat in the future.
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8.
Effects of Local Administration of Tranexamic Acid on Reducing Postoperative Blood Loss in Surgeries for Closed, Sanders III-IV Calcaneal Fractures: A Randomized Controlled Study
Zhong L, Liu Y, Wang Y, Wang H
Indian journal of orthopaedics. 2021;55(Suppl 2):418-425
Abstract
PURPOSE To investigate whether local administration of tranexamic acid (TXA) is effective in postoperative blood loss reduction in surgeries for Sanders III-IV calcaneal fractures. METHODS Calcaneal fracture patients who were hospitalized in our hospital from August 2014 to April 2018 and underwent open reduction internal fixation (ORIF) via lateral approach with an L-shaped incision were included in the present study. 53 Patients were randomly divided into three groups, groups A (17), B (17) and C (19). Twenty milliliters of 10 mg/ml and 20 mg/ml TXA solution were perfused into the incision of patients in group A and group B, respectively. Twenty milliliters of saline were perfused into the incision of patients in group C as control. The volume of postoperative drainage, postoperative blood test, coagulation test, and wound complications were analyzed to evaluate the effectiveness of local administration of TXA on blood loss reduction. RESULTS The amount of drainage at 24 and 48 h after the procedure was 110 ± 170, 30 ± 10 ml and 130 ± 160, 20 ± 17 ml for patients in group A and group B, respectively. The corresponding numbers for patients in group C were 360 ± 320, 20 ± 10 ml. The difference between group A and group C was statistically significant, so was the difference between group B and group C. No statistically significant difference was found between group A and group B. Postoperative blood test results revealed that the levels of hemoglobin and hematocrit were significantly higher in group A and group B when each compared to that of group C. In contrast, no difference was found between group A and group B. No significant difference was found between each experimental group and the control group in terms of platelet counts, prothrombin time (P.T.), activated partial prothrombin time (APTT), and wound complications. CONCLUSION Local administration of TXA is effective in the reduction of postoperative blood loss in surgeries for Sanders III-IV types of calcaneal fractures without notably associated side effects.
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9.
Effects of Tourniquet Application on Faster Recovery after Surgery and Ischemia-Reperfusion Post-Total Knee Arthroplasty, Cementation through Closure versus Full-Course and Nontourniquet Group
Cao Q, Wu Q, Liu Y, He Z, Cong Y, Meng J, Zhao J, Bao N
The journal of knee surgery. 2021
Abstract
Pneumatic tourniquets are used in total knee arthroplasty (TKA) for surgical field visualization and improved cementation; however, their use is controversial. This study aimed to assess the effects of tourniquet application on faster recovery post-TKA. Our hypothesis was that inflammation and limb function would be similar with different tourniquet applications. A prospective randomized double-blinded trial assessed tourniquets effects on postoperative pain, swelling, and early outcome in TKA. In present study, 50 TKAs were enrolled in each group as follows: full course (FC), cementation through closure (CTC), and no tourniquet (NT), CTC as treatment group while FC and NT as control groups. Topical blood samples of 3 mL from the joint cavity and drainage bags were obtained at special time point. At last, all samples such as tumor necrosis factor-a (TNF-a), C-C motif chemokine ligand 2 (CCL2), pentraxin 3 (PTX3), prostaglandin E2 (PGE2), superoxide dismutase 1 (SOD1), and myoglobin (Mb) were detected by ELISA. Active and passive range of motion (ROM) values, pain score by the visual analog scale (VAS), change of thigh circumference were recorded at special time point as well. In topical blood, the change of inflammatory factors, such as TNF-a, PTX3, CCL2, PGE2, SOD1, and Mb, was lower in CTC and NT groups than in FC group (p < 0.01 and 0.05). Although VAS and ROM were comparable preoperatively in three groups (p > 0.05), the perimeter growth rate was lower, pain scores (VAS) were reduced, and ROM values were improved in CTC and NT groups compared with FC group at T4, T5, and T6 postoperatively (p < 0.01 and 0.05). Improved therapeutic outcome was observed in the CTC group, indicating patients should routinely undergo TKA with cementation through closure tourniquet application.
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10.
Intravenous Tranexamic Acid Improves the Intraoperative Visualization of Endoscopic Sinus Surgery for High-Grade Chronic Rhinosinusitis: A Randomized, Controlled, Double-Blinded Prospective Trial
Yang W, Gou H, Li H, Liu Y, Wan Y, Wang C, Wang G, Zhang L
Frontiers in surgery. 2021;8:771159
Abstract
Objective: Intraoperative bleeding during endoscopic sinus surgery (ESS) for high-grade rhinosinusitis can be serious and can further obscure the surgical field. This study was designed to evaluate the effect of tranexamic acid (TXA) on the surgical visualization of ESS for high-grade rhinosinusitis. Methods: In total, 60 patients with high-grade chronic rhinosinusitis (Lund-Mackay score 12 or greater) treated by ESS were randomized into two groups: the control group (Group C) or the TXA group (Group T). Each group included 30 patients. Patients in Group T received intravenous TXA, and those in Group C received normal saline. The Boezaart grading scale (BS) score was assessed as the primary outcome. Total blood loss (TBL), whole blood coagulation, and fibrinolysis were assessed by Sonoclot analysis, and complications were recorded and compared between the groups. Result: A significant difference was found in the BS score between Group T and Group C [2.02 (1.88-2.05) vs. 2.27 (2.13-2.41), P = 0.011]. Increases in platelet function (PF) and fibrin degradation time (FDT) were assessed during the operation and showed significant differences between Group T and Group C (P = 0.040 for PF; P = 0.010 for FDT). No difference in complications was found between the two groups. Conclusion: A 15 mg/kg bolus of intravenous TXA before surgery can improve the surgical visualization of ESS for high-grade chronic rhinosinusitis without causing significant adverse effects. Intravenous TXA may be beneficial in ESS for high-grade chronic rhinosinusitis. Clinical Trial Registration: https://www.chictr.org.cn/edit.aspx?pid=121653&htm=4.