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.

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.

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.

A Retrospective Analysis of the American Thrombosis and Hemostasis Network Dataset Describing Outcomes of Dental Extractions in Persons with Hemophilia.

INTRODUCTION: dental extractions (DEs) in persons with hemophilia A or B (PWH-A or PWH-B) are often associated with bleeding and needing hemostatic therapies (HTs). AIM: to analyze the American Thrombosis and Hemostasis Network (ATHN) dataset (ATHNdataset) to assess trends, uses and impacts of HT on bleeding outcomes following DEs. METHODS: PWH seen at ATHN affiliates who underwent DEs and opted to share their data with the ATHNdataset between 2013-2019 were identified. The type of DEs, use of HT and bleeding outcomes were assessed. RESULTS: Among 19,048 PWH ≥2 years of age, 1157 underwent 1301 episodes of DE. Those on prophylaxis experienced a nonsignificant reduction in dental bleeding episodes. Standard half-life factor concentrates were used more often than extended half-life products. PWHA were more likely to undergo DE in the first 30 years of life. Those with severe hemophilia were less likely to undergo DE than those with a mild disease (OR: 0.83; 95% CI: 0.72-0.95). PWH with inhibitors had statistically significantly increased odds of dental bleeding (OR: 2.09, 95% CI; 1.21-3.63). CONCLUSION: our study showed that persons with mild hemophilia and younger age were more likely to undergo DE; the presence of inhibitors increased the likelihood of bleeding, while those with prophylaxis and receiving HT experienced a non-statistically significant reduction in bleeding.

Combination of Intravenous and Intra-Articular Application of Tranexamic Acid and Epsilon-Aminocaproic Acid in Primary Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

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.

Tranexamic versus aminocaproic acids in patients with total hip arthroplasty: a retrospective study.

BACKGROUND: Recently, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been applied in total hip arthroplasty (THA). However, doubts in clinicians' minds about which medicine is more efficient and economical in THA need to be clarified. Therefore, this study compared the efficacy and cost of the intraoperative administration of TXA and EACA per surgery in decreasing perioperative blood transfusion rates in THA. METHODS:  This study enrolled patients who underwent THA between January 2019 to December 2020. A total of 295 patients were retrospectively divided to receive topical combined with intravenous TXA (n = 94), EACA (n = 97) or control (n = 104). The primary endpoints included transfusions, estimated perioperative blood loss, cost per patient and the drop in the haemoglobin and haematocrit levels. RESULTS: Patients who received EACA had greater total blood loss, blood transfusion rates, changes in HGB levels and mean cost of blood transfusion per patient (P < 0.05) compared with patients who received TXA. In addition, both TXA and EACA groups had significantly fewer perioperative blood loss, blood transfusion, operation time and changes in haemoglobin and haematocrit levels than the control group (P < 0.05). Cost savings in the TXA and EACA groups were 736.00 RMB and 408.00 RMB per patient, respectively. CONCLUSIONS: The application of perioperative antifibrinolytics notably reduces the need for perioperative blood transfusions. What's more, this study demonstrated that TXA is superior to EACA for decreasing blood loss and transfusion rates while at a lower cost per surgery. These results indicate that TXA may be the optimum antifibrinolytics for THA in Chinese area rather than EACA.

Disseminated Intravascular Coagulation With Excessive Fibrinolysis Following Diagnostic Prostatic Biopsy for Prostate Cancer.

The most common hematological disorder associated with prostate cancer is disseminated intravascular coagulation (DIC). In most cases, cancer patients with DIC have compensated fibrinolysis with a low incidence of bleeding. However, DIC with excessive fibrinolysis is a rare albeit life-threatening variant that can present with massive bleeding and is thought to occur due to the unique properties of neoplastic cells of prostate cancer that activate both procoagulant and anticoagulant pathways simultaneously. Depending on the shift of the intricate balance between the two forces, the net result can be either systemic micro- (DIC) or macro-thrombi, deep venous thrombosis (DVT) or pulmonary embolism, or a bleeding syndrome from excessive vicious activation of fibrinolysis. Here, we present a unique case of suspected prostate cancer who underwent a diagnostic prostatic biopsy. Subsequently, he developed massive hematuria requiring intensive care unit admission with multiple supportive blood products. Additionally, he was administered epsilon-aminocaproic acid with a prophylactic dose of heparin, with prompt resolution of bleeding. After stabilization, he was discharged with planned outpatient chemotherapy. However, he subsequently presented with lower extremity DVT within a week, which led to a stroke in the setting of a patent foramen ovale. This unique case report highlights how a change in the intricate balance of the coagulation cascade causes a polar shift in clinical presentation and complications.

Safety of antifibrinolytics in 6583 pediatric patients having craniosynostosis surgery: A decade of data reported from the multicenter Pediatric Craniofacial Collaborative Group.

BACKGROUND: Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid are effective at reducing blood loss and transfusion in pediatric patients having craniofacial surgery. The Pediatric Craniofacial Collaborative Group has previously reported low rates of seizures and thromboembolic events (equal to no antifibrinolytic given) in open craniofacial surgery. AIMS: To query the Pediatric Craniofacial Collaborative Group database to provide an updated antifibrinolytic safety profile in children given that antifibrinolytics have become recommended standard of care in this surgical population. Additionally, we include the population of younger infants having minimally invasive procedures. METHODS: Patients in the Pediatric Craniofacial Collaborative Group registry between June 2012 and March 2021 having open craniofacial surgery (fronto-orbital advancement, mid and posterior vault, total cranial vault remodeling, intracranial LeFort III monobloc), endoscopic cranial suture release, and spring mediated cranioplasty were included. The primary outcome is the rate of postoperative complications possibly attributable to antifibrinolytic use (seizures, seizure-like activity, and thromboembolic events) in infants and children undergoing craniosynostosis surgery who did or did not receive antifibrinolytics. RESULTS: Forty-five institutions reporting 6583 patients were included. The overall seizure rate was 0.24% (95% CI: 0.14, 0.39%), with 0.20% in the no Antifibrinolytic group and 0.26% in the combined Antifibrinolytic group, with no statistically reported difference. Comparing seizure rates between tranexamic acid (0.22%) and epsilon-aminocaproic acid (0.44%), there was no statistically significant difference (odds ratio = 2.0; 95% CI: 0.6, 6.7; p = .257). Seizure rate was higher in patients greater than 6 months (0.30% vs. 0.18%; p = .327), patients undergoing open procedures (0.30% vs. 0.06%; p = .141), and syndromic patients (0.70% vs. 0.19%; p = .009). CONCLUSIONS: This multicenter international experience of pediatric craniofacial surgery reports no increase in seizures or thromboembolic events in those that received antifibrinolytics (tranexamic acid and epsilon-aminocaproic acid) versus those that did not. This report provides further evidence of antifibrinolytic safety. We recommend following pharmacokinetic-based dosing guidelines for administration.

Epsilon Aminocaproic Acid's Safety and Efficacy in Pediatric Surgeries Including Craniosynostosis Repair: A Review of the Literature.

Craniosynostosis, the premature fusion of skull sutures in children, requires surgical correction. This procedure routinely requires allogeneic blood transfusions, which are associated with multiple risks of their own. Since 2008, antifibrinolytics tranexamic acid (TXA) and epsilon aminocaproic acid (EACA or Amicar) have been widely used. There is literature comparing the two agents in scoliosis and cardiothoracic surgery, but the literature comparing the two agents in pediatric craniofacial surgery (CF) is limited. Tranexamic acid use is more common in pediatric CF surgery and has been thoroughly studied; however, it costs about three times as much as EACA and has been associated with seizures. This study compiles the literature assessing the safety and efficacy of EACA in reducing blood loss and transfusion volumes in children and explores its potential use in pediatric CF surgery. Papers from 2000 to 2021 regarding the effectiveness and safety of EACA in Pediatric scoliosis, cardiothoracic, and craniosynostosis surgery were reviewed and compiled. Papers were found via searching PubMed and Cochrane databases with the key terms: Epsilon aminocaproic acid, EACA, Amicar, Tranexamic acid, TXA, craniosynostosis, scoliosis, cardiothoracic, and pediatric. Prospective studies, retrospective studies, and meta-analyses were included. Twenty-nine papers were identified as pertinent from the literature searched. Four were meta-analyses, 14 were retrospective, and 11 were prospective. Of these papers, seven were of cardiac surgery, 12 were of scoliosis, and nine were of craniosynostosis. During our search, EACA has been shown to consistently reduce blood transfusion volumes compared to control. However, it is not as effective when compared to TXA. EACA has a similar safety profile to TXA but has a reduced risk of seizures. There are not many studies of EACA in craniosynostosis repair, but the existing literature shows promising results for EACA's efficacy and safety, warranting more studies.

The effect of antifibrinolytic agents in periacetabular osteotomy: A systematic review and meta-analysis.

BACKGROUND: Periacetabular osteotomy (PAO) is a major hip preservation surgery for developmental dysplasia of the hip. It is inevitably associated with significant blood loss, so it requires frequent transfusions and could be a cause of perioperative morbidity. However, to date, a large number of studies has not evaluated the effect of antifibrinolytic agents in PAO. Therefore we performed a systematic review and meta-analysis to assess if antifibrinolytics would be effective in reducing blood loss and transfusion rate after PAO surgery. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before April 4, 2020, that investigated the effect of antifibrinolytic agents in PAO. A pooled analysis was designed to identify differences between antifibrinolytic and control groups focusing on blood loss, transfusion, operation time, postoperative venous thromboembolism (VTE), and length of hospital stay. RESULTS: We included five studies involving 507 patients (antifibrinolytic group: 256; control group: 251). The pooled analysis showed that the control group had a greater total estimated blood loss (EBL) than the antifibrinolytic group (mean difference [MD]=-257.60mL, 95% confidence interval [CI] -389.68 to -125.53, p=0.0001), but there were no statistical differences in intraoperative EBL (MD=-46.46mL, 95% CI: -192.57 to 99.64, p=0.53). The allogenic transfusion rate was higher in the control group than in the antifibrinolytic group (odds ratio [OR] 0.21, 95% CI: 0.10-0.43, p<0.0001), but there was no difference in the autogenic transfusion rate (OR 0.35, 95% CI: 0.09-1.43, p=0.14). The pooled result showed no difference in operation time (MD=9.13min, 95% CI: -8.54 to 26.80, p=0.31). For the VTE rate, a pooled analysis was not conducted due to the lack of data. The length of hospital stay showed no differences (MD=-0.51 days, 95% CI: -1.17 to 0.16, p=0.13). CONCLUSIONS: Antifibrinolytic use in PAO has positive effects in terms of reduced total EBL and allogenic transfusion rate. LEVEL OF EVIDENCE: III; meta-analysis.

Comparative Analysis of Topical Versus Intravenous Administration of Epsilon-Aminocaproic Acid on Blood Management in Total Knee Arthroplasty.

Introduction: Although the use of antifibrinolytics to reduce perioperative blood loss during total knee arthroplasty (TKA) has shown unequivocal benefit in regard to blood conservation, the best route of administration remains in question. This study tested the hypothesis that topical delivery of epsilon-aminocaproic acid (EACA) was superior to intravenous (IV) administration in the setting of primary TKA. Methods: This cross-sectional study included a six-year retrospective chart review of TKA patients done by a single surgeon. Post-operative hemoglobin levels and the incidence of blood transfusions were compared among three patient subgroups: no EACA, topical EACA, or IV EACA. Key outcome measures included post-operative hemoglobin, need for post-operative transfusion, and length of hospital stay. Results: Of the 668 patients included in this study, 351 (52.5%) received IV EACA, 298 (44.6%) received topical EACA, and 19 (2.8%) received no EACA. For the three-way comparisons, significant differences were observed for post-operative mean hemoglobin on day one (p < 0.001), day two (p < 0.001), and day three (p = 0.004), with consistently higher means for participants in the topical group. Eight patients required transfusions in the IV EACA group, but none were needed in the topical EACA group (p = 0.027). Length of stay was shortest for patients in the topical group, with 66% hospitalized for two days, while 84% of the IV group remained hospitalized for three days (p < 0.001). Conclusions: The topical delivery of EACA is superior to IV administration with respect to blood conservation for patients undergoing primary TKA.

Local administration of epsilon-aminocaproic acid reduces post-operative blood loss from surgery for closed, Sanders III-IV calcaneal fractures.

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.

INTRAARTICULAR EPSILON AMINOCAPROIC ACID VERSUS TRANEXAMIC ACID IN TOTAL KNEE ARTHROPLASTY.

OBJECTIVE: To examine and compare the clinical efficacy of intraarticular epsilon aminocaproic acid (EACA) and tranexamic acid (TXA) in total knee arthroplasty (TKA). METHODS: This study was a prospective, single-center, double-blinded randomized controlled trial, including sixty patients with osteoarthritis of the knee divided into two groups of 30 patients. In the TXA group, 1 g of TXA (0.05 g/ml) was applied intraarticularly, and in the EACA group, 4 g of EACA (0.2 g/ml) was applied intraarticularly. Serum hemoglobin (Hgb) and hematocrit (Htb) were measured during the preoperatively and 24 and 48 hours postoperatively. The range of motion and pain were evaluated by clinical examination. To evaluate knee function before and 2 months after surgery, the Western Ontario and McMaster Universities Index (WOMAC) questionnaire was used. RESULTS: In total, 56 (93.3%) patients were evaluated up to the second postoperative month. No significant difference between the groups (p > 0.05) was found in the decrease in Hgb or Htb at 24 or 48 hours. Regarding assessment of the pain, WOMAC score and gain in knee flexion, no significant advantages up to 60 days after surgery (p > 0.05) were found. CONCLUSIONS: The decrease in Hgb and Htb during the first 48 hours postoperatively and the risk of transfusion were similar with the intraarticular use of 1 g of TXA and 4 g of EACA in TKA. The possible benefits regarding knee pain, gain in flexion and function were also similar for the two drugs. Level of Evidence II, Randomized, Double-Blinded, Single-Centre, Prospective Clinical Trial.

OBJETIVO: Avaliar e comparar a eficácia clinica do uso intra-articular do ácido épsilon aminocaproico (AEAC) versus o ácido tranexâmico (ATX) na prótese total do joelho. MÉTODOS: Estudo clínico prospectivo, centro-único, duplo-cego e randomizado. Sessenta pacientes com osteoartrose de joelho foram incluídos. Os participantes foram divididos em dois grupos de 30 pacientes. No grupo ATX, foi aplicado 1 g de ATX (0.05 g/ml) intra-articular e, no grupo AEAC, foram aplicados 4 g de AEAC (0.2 g/ml) intra-articular. Valores séricos da hemoglobina (Hb) e hemtatócrito (Ht) foram dosados no pré-operatório e com 24 e 48 horas após a cirurgia. A amplitude de movimento e a dor também foram avaliadas no exame clínico. O índice WOMAC foi utilizado para avaliar a função do joelho antes e após dois meses da cirurgia. RESULTADOS: Foram avaliados 56 (93.3%) pacientes até o segundo mês pós-operatório. Depois da cirurgia, não houve diferenças entre os grupos (p > 0.05) na queda do valor de Hb e Ht com 24 ou 48 horas. Com relação à avaliação da dor, WOMAC e ganho de flexão do joelho, não houve vantagem significativa para nenhum dos grupos até os 60 dias depois da cirurgia(p > 0.05). CONCLUSÃO: A queda do valor da Hb e do Ht durante as primeiras 48 horas pós-operatórias e o risco de transfusão foram similares com o uso intra-articular de 1 g de ATX e 4 g de AEAC na artroplastia total do joelho. Os possíveis benefícios com relação ao controle da dor, ganho de flexão e função foram similares entre as duas drogas. Nível de Evidência II, Ensaio-Clínico Prospectivo, Randomizado, Duplo Cego, Centro-Único.

Intraarticular epsilon aminocaproic acid versus tranexamic acid in total knee arthroplasty / Acido épsilon aminocaproico intra-articular versus acido tranexâmico na prótese total do joelho

ABSTRACT Objective: To examine and compare the clinical efficacy of intraarticular epsilon aminocaproic acid (EACA) and tranexamic acid (TXA) in total knee arthroplasty (TKA). Methods: This study was a prospective, single-center, double-blinded randomized controlled trial, including sixty patients with osteoarthritis of the knee divided into two groups of 30 patients. In the TXA group, 1 g of TXA (0.05 g/ml) was applied intraarticularly, and in the EACA group, 4 g of EACA (0.2 g/ml) was applied intraarticularly. Serum hemoglobin (Hgb) and hematocrit (Htb) were measured during the preoperatively and 24 and 48 hours postoperatively. The range of motion and pain were evaluated by clinical examination. To evaluate knee function before and 2 months after surgery, the Western Ontario and McMaster Universities Index (WOMAC) questionnaire was used. Results: In total, 56 (93.3%) patients were evaluated up to the second postoperative month. No significant difference between the groups (p > 0.05) was found in the decrease in Hgb or Htb at 24 or 48 hours. Regarding assessment of the pain, WOMAC score and gain in knee flexion, no significant advantages up to 60 days after surgery (p > 0.05) were found. Conclusions: The decrease in Hgb and Htb during the first 48 hours postoperatively and the risk of transfusion were similar with the intraarticular use of 1 g of TXA and 4 g of EACA in TKA. The possible benefits regarding knee pain, gain in flexion and function were also similar for the two drugs. Level of Evidence II, Randomized, Double-Blinded, Single-Centre, Prospective Clinical Trial.

RESUMO Objetivo: Avaliar e comparar a eficácia clinica do uso intra-articular do ácido épsilon aminocaproico (AEAC) versus o ácido tranexâmico (ATX) na prótese total do joelho. Métodos: Estudo clínico prospectivo, centro-único, duplo-cego e randomizado. Sessenta pacientes com osteoartrose de joelho foram incluídos. Os participantes foram divididos em dois grupos de 30 pacientes. No grupo ATX, foi aplicado 1 g de ATX (0.05 g/ml) intra-articular e, no grupo AEAC, foram aplicados 4 g de AEAC (0.2 g/ml) intra-articular. Valores séricos da hemoglobina (Hb) e hemtatócrito (Ht) foram dosados no pré-operatório e com 24 e 48 horas após a cirurgia. A amplitude de movimento e a dor também foram avaliadas no exame clínico. O índice WOMAC foi utilizado para avaliar a função do joelho antes e após dois meses da cirurgia. Resultados: Foram avaliados 56 (93.3%) pacientes até o segundo mês pós-operatório. Depois da cirurgia, não houve diferenças entre os grupos (p > 0.05) na queda do valor de Hb e Ht com 24 ou 48 horas. Com relação à avaliação da dor, WOMAC e ganho de flexão do joelho, não houve vantagem significativa para nenhum dos grupos até os 60 dias depois da cirurgia(p > 0.05). Conclusão: A queda do valor da Hb e do Ht durante as primeiras 48 horas pós-operatórias e o risco de transfusão foram similares com o uso intra-articular de 1 g de ATX e 4 g de AEAC na artroplastia total do joelho. Os possíveis benefícios com relação ao controle da dor, ganho de flexão e função foram similares entre as duas drogas. Nível de Evidência II, Ensaio-Clínico Prospectivo, Randomizado, Duplo Cego, Centro-Único.

The Efficacy and Safety of Epsilon-Aminocaproic Acid for Perioperative Blood Management in Spinal Fusion Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Perioperative blood loss is a major concern in spinal fusion surgery and often requires blood transfusion. A large amount of perioperative blood loss might increase the risks of various perioperative complications. Recent clinical studies have focused on the perioperative administration of epsilon-aminocaproic acid (EACA) in spinal fusion surgery. The aim of this review was to evaluate the efficacy and safety of EACA in spinal fusion surgery. METHODS: Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane Central Register of Controlled Trials) were systematically searched up to April 2021. Data on perioperative blood loss, blood transfusion, and complications were extracted and analyzed by RevMan software. RESULTS: Six randomized controlled studies comprising 398 patients undergoing spinal fusion surgery were included in this systematic review. Compared with the control group, the EACA group had significantly lower total perioperative blood loss, postoperative blood loss, postoperative hemoglobin, postoperative blood transfusion units, total blood transfusion units, and postoperative red blood cell transfusion units. Additionally, no significant differences were observed between the EACA and control groups in intraoperative blood loss, intraoperative blood transfusion units, intraoperative crystalloid administered, hospital stays, operative time, perioperative respiratory complications, and wound bleeding. CONCLUSIONS: EACA in patients undergoing spinal fusion surgery is effective in perioperative hemostasis without increasing the incidence of postoperative complications. However, more large-scale trials are needed to examine the long-term adverse side effects of EACA in spinal fusion surgery.

A New Insight on the Radioprotective Potential of Epsilon-Aminocaproic Acid.

Background and objectives: The aim of the study was to scrutinize the ability of epsilon-aminocaproic acid (EACA) to prevent radiation-induced damage to human cells. Materials and Methods: Human peripheral blood mononuclear cells (PBMCs) were exposed to ionizing radiation at three low doses (22.62 mGy, 45.27 mGy, and 67.88 mGy) in the presence of EACA at the concentration of 50 ng/mL. Results: EACA was able to prevent cell death induced by low-dose X-ray radiation and suppress the formation of reactive oxygen species (ROS). EACA also demonstrated a capacity to protect DNA from radiation-induced damage. The data indicated that EACA is capable of suppression of radiation-induced apoptosis. Comparative tests of antioxidative activity of EACA and a range of free radical scavengers showed an ability of EACA to effectively inhibit the generation of ROS. Conclusions: This study showed that the pretreatment of PBMCs with EACA is able to protect the cells from radiation-elicited damage, including free radicals' formation, DNA damage, and apoptosis.

Safety and efficacy of epsilon aminocaproic acid (EACA) as an antihemorrhagic drug in bilateral one stage total knee arthroplasty: A double-blind randomized controlled trial.

BACKGROUND: Antifibrinolytic drugs are widely used to minimize blood loss and transfusion requirements in total knee arthroplasty (TKA). Although tranexamic acid (TXA) has been widely studied for its use in TKA, there are limited studies on epsilon-aminocaproic acid (EACA). METHODS: In a double-blind randomized control trial, all patients (n = 91) operated with bilateral simultaneous TKA were randomly given either intravenous EACA or placebo (normal saline). A single surgeon performed the TKA with posterior-stabilized implants under tourniquet. A suction drain was placed and kept for 48 h postoperatively. The intraoperative blood loss and drain output were calculated. The postoperative hemoglobin (Hb), drop in Hb, total blood loss, and number of blood transfusions in each group were calculated. RESULTS: Both of the groups were comparable in terms of age, sex, body mass index, and pre-operative Hb. There was a significant difference between the EACA group and control group in terms of intraoperative blood loss (150 ml vs. 165 ml, P = 0.01), drain output (494 ml vs. 1062 ml, P < 0.001), postoperative Hb (9.9 g/dl vs. 8.6 g/dl, P = 0.002), drop in Hb (2.2 g/dl vs. 3.1 g/dl, P = 0.026) and transfusion rate (median transfusion 0 vs. 1, P < 0.001). The total blood loss, as calculated by the Hb balance method, was significantly less (P < 0.001) in the EACA group (0.99 l) compared with the control group (2.71 l). None of the patients developed any adverse reaction/complication to the drug. CONCLUSION: Intraoperative administration of EACA significantly decreased the blood loss and postoperative transfusion rates compared with no antifibrinolytic therapy in bilateral simultaneous TKA.

Comparison of intraoperative tranexamic acid and epsilon-aminocaproic acid in cardiopulmonary bypass patients.

Objective: To compare tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: Over a consecutive 2-year period, 824 adult cardiac surgery patients who received TXA during an EACA shortage were compared with 778 patients who received EACA postshortage. Patient characteristics and process and outcome variables were collected through chart review and database queries. This retrospective analysis used inverse probability of treatment weighting to control for confounding by indication, and propensity scores were calculated using a logistic regression model. Results: In adjusted models, overall transfusion rates for the TXA cohort (odds ratio [OR], 0.94; 95% confidence interval [95% CI], 0.81-1.10) and administration of platelets (OR, 1.04; 95% CI, 0.85-1.27), red blood cells (OR, 0.93; 95% CI, 0.80-1.09), fresh frozen plasma (OR, 1.00; 95% CI, 0.79-1.25), and cryoprecipitate (OR, 1.08; 95% CI, 0.71-1.64) were equivalent to the EACA cohort. In addition, there was no statistical difference with respect to stroke, seizure, mortality, reoperation for bleeding, chest tube drainage, and acute kidney injury. Patients who received TXA had shorter ventilator times (difference in medians -1.33 hours [95% CI, -1.86 to -0.80]) and lower postsurgical charges (difference of medians -$2913 [95% CI, -5147 to -679]). Conclusions: Substituting TXA for EACA during cardiac surgery with cardiopulmonary bypass did not change transfusion rate or amount, nor was there a significant difference in chest tube drainage. Patients who received TXA had a statistically significant but not clinically significant lower postoperative ventilator times and charges without an increase in mortality, stroke, reoperation for bleeding, acute kidney injury, or seizures.

A randomized, double-blinded trial comparing the effectiveness of tranexamic acid and epsilon-aminocaproic acid in reducing bleeding and transfusion in cardiac surgery.

Objectives: To compare the effectiveness of epsilon aminocaproic acid (EACA) to tranexamic acid (TA) in reducing blood loss and transfusion requirements in patients undergone cardiac surgery under cardiopulmonary bypass. Design: Randomized, double blinded study. Outcome variables collected included; baseline demographic characteristics, type of surgery, amount of 24 hour chest tube drainage, amount of 24 hour blood products administered, 30 day mortality and morbidity and length of stay. We analyzed the data using parametric and non-parametric tests as appropriate. Setting: Single center tertiary-care university hospital setting. Participants: 114 patients who had undergone cardiac surgery under cardiopulmonary bypass. Interventions: Standard dose of intra-operative EACA or TA was compared in patients undergone cardiac surgery under cardiopulmonary bypass. Results: There was no statistically significant difference between groups when analyzing chest tube drainage. However, there was a significant difference in the administration of any transfusion (PRBC's, FFP, platelets) intra-operatively to 24 hours postoperatively, with less transfusion in patients receiving EACA compared to TA (25% vs. 44.8%, respectively P = 0.027). Additionally, there was no significant difference in terms of adverse events during the one month follow up period. Conclusion: The findings of this study suggest that EACA and TA have similar effects on chest tube drainage but EACA is associated with fewer transfusions in CABG alone surgeries. Our results suggest that EACA can be used in a similar fashion to TA which may result in a cost and morbidity advantage.

Epsilon-aminocaproic acid versus tranexamic acid in total knee arthroplasty: a meta-analysis study.

INTRODUCTION: Total knee arthroplasty (TKA) surgery can be associated with significant blood loss. Among the problems associated with such blood loss is the need for transfusions of banked blood [1]. Transfusions not only have a financial consequence but also carry a small risk of disease transmission to the patient. Antifibrinolytics have been successfully used to reduce transfusion requirements in elective arthroplasty patients. The objective of this meta-analysis is to determine which of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) is more effective for reducing peri-operative blood loss, and lessening the need for blood transfusion following knee arthroplasty surgery. MATERIALS AND METHODS: MEDLINE, Embase and CINAHL databases were searched for relevant articles published between January 1980 to January 2018 for the purpose of identifying studies comparing TXA and EACA for TKA surgery. A double-extraction technique was used, and included studies were assessed regarding their methodological quality prior to analysis. Outcomes analysed included blood loss, pre- and post-operative haemoglobin, number of patients requiring transfusion, number of units transfused, operative and tourniquet time, and complications associated with antifibrinolytics. RESULTS: Three studies contributed to the quantitative analysis of 1691 patients, with 743 patients included in the TXA group and 948 in the EACA group. Estimated blood loss was similar between the two groups [95% confidence interval (CI) -0.50, 0.04; Z = 1.69; P = 0.09]. There were no differences between the two groups regarding the percentage of patients requiring transfusion (95% CI 0.14, 4.13; Z = 0.31; P = 0.76). There was no difference in the pre- and post-operative haemoglobin difference between the two groups (95% CI -0.36, 0.24; Z = 0.38; P = 0.70). There was no difference in the average number of transfused units (95% CI -0.53, 0.25; Z = 0.71; P = 0.48). There was no difference in the operative (95% CI -0.35, 0.36; Z = 0.04; P = 0.97) or tourniquet time (95% CI -0.16, 0.34; Z = 0.72; P = 0.47). Similarly, there was no difference in the percentage of venous thromboembolism between the two groups (95% CI 0.17, 2.80; Z = 0.51; P = 0.61). CONCLUSIONS: This study did not demonstrate TXA to be superior to EACA. In fact, both antifibrinolytic therapies demonstrated similar efficacy in terms of intra-operative blood loss, transfusion requirements and complication rates. Currently EACA has a lower cost, which makes it an appealing alternative to TXA for TKA surgery. LEVEL OF EVIDENCE: 3.

The Efficacy and Safety of Epsilon-Aminocaproic Acid for Blood Loss and Transfusions in Spinal Deformity Surgery: A Meta-Analysis.

OBJECTIVE: To assess the efficacy and safety of epsilon-aminocaproic acid (EACA) in reducing the blood loss and transfusion volume during open spinal deformity surgery. METHODS: A systematic search was conducted for all studies written in English published on or before October 2018 in PubMed, EMBASE, and the Cochrane Library that compared antifibrinolytic agents with placebos for open spinal deformity surgeries. The primary outcomes included the total blood loss, intraoperative, and postoperative blood loss, transfusions volume and complication rate. RESULTS: Seven studies that included 525 patients who were diagnosed with spinal deformity. Compared with placebo, the patients who received EACA showed a reduction in the postoperative blood loss (mean difference [MD] -249.80; 95% confidence interval [CI] -375.65 to -123.95; P = 0.0001) and total blood loss (MD -670.30; 95% CI -1142.63 to -197.98; P = 0.005). Furthermore, the patients treated with EACA received approximately 1.67 fewer units of blood (MD -1.67; 95% CI -3.10 to -0.24; P = 0.02). However, in this cohort, no statistically significant differences were observed in the intraoperative blood loss (MD -452.19; 95% CI -1082.21 to 177.83; P = 0.16) and complication rate (odds ratio 0.73; 95% CI 0.16-3.24; P = 0.68). CONCLUSIONS: This meta-analysis demonstrated that EACA could be safe and potentially efficacious for reducing blood loss and transfusions volume in patients with spinal deformity surgeries when compared with placebo. In light of the significant heterogeneity, the findings of this meta-analysis should be confirmed in methodologically rigorous and adequately powered clinical trials.