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Background: Tranexamic acid (TXA) has long been the antifibrinolytic hemostatic drug of choice for orthopedic surgery. In recent years, the hemostatic effect of epsilon aminocaproic acid (EACA) has gradually been recognized by orthopedic surgeons and has begun to be used in hip and knee arthroplasty with little mention of the comparison of these two drugs; Therefore, this study compared the efficacy and safety of EACA and TXA in the perioperative period of elderly patients with trochanteric fractures to verify whether EAC could be a "qualified alternative" to TXA and to provide theoretical support for the clinical application of TXA., Methods: Two hundred and forty-three patients who received proximal femoral nail antirotation (PFNA) for trochanteric fractures from January 2021 to March 2022 at our institution were included and divided into the EACA group (n = 146) and the TXA group. (n = 97) determined by the drugs used in the perioperative period The main observations were blood loss and blood transfusion.The second second outcome was blood routine, coagulation, Hospital complications and complications after discharge., Results: The perioperative EACA patients had significantly lower significant blood loss (DBL) than the TXA group (p < 0.0001) and statistically significant lower C-reactive protein in the EACA group than in the TXA group on postoperative day 1 (p = 0.022). Patients on perioperative TXA had better postoperative day one (p = 0.002) and postoperative day five erythrocyte width than the EACA group (p = 0.004). However, there was no statistically significant difference between the two groups in the remaining indicators in both drugs: blood items, coagulation indicators, blood loss, blood transfusion, length of hospital(LOH), total hospital expense, and postoperative complications (p > 0.05)., Conclusion: The hemostatic effects and safety of EACA and TXA in the perioperative application of trochanteric fractures in the elderly are essentially similar, and EACA can be considered for use as an alternative to TXA, increasing the flexibility of physicians to use it in the clinical setting. However, the limited sample size included necessitated a high-quality, large sample of clinical studies and long-term follow-up., (© 2023. The Author(s).)

Background: Antifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI)., Study Design and Methods: We conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life-threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis., Results: Of 448 children included, median (interquartile range) age was 7 (2-15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety-three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty-seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p = .002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre-LTH, and total weight-adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0-10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis., Conclusion: Administration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients., (© 2023 AABB.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022 John Wiley & Sons Ltd.)

Objectives: To examine E-aminocaproic acid effectiveness in reducing transfusion requirements in overall and less-invasive cardiac surgery, and to assess its safety., Design: Retrospective cohort study., Setting: Single-center tertiary academic medical center., Participants: A total of 19,111 adult patients who underwent elective surgery requiring cardiopulmonary bypass from January 1, 2008, through December 31, 2016., Interventions: None., Measurements and Main Results: Propensity matching was used to create well-balanced groups and separately compare both overall cohort and less-invasive surgery with and without E-aminocaproic acid. Supplementary zero-inflated negative binomial regression analysis was used because outcome data were zero-inflated. Effectiveness was assessed by transfusion requirements, and safety by comparison of in-hospital outcomes. In the overall cohort, patients receiving E-aminocaproic acid received fewer red blood cells postoperatively and fewer intra- and postoperativel blood products. In a less-invasive cohort, there was no significant difference in red blood cell transfusion either intra- or postoperatively, but the E-aminocaproic group received fewer intra- and postoperative platelets, intraoperative cryoprecipitate, and postoperative plasma. There were no significant differences for in-hospital outcomes in both less-invasive and overall cohorts., Conclusions: The reduction of postoperative red blood cell requirement observed when analyzing the overall cohort did not translate to less-invasive cardiac surgery in the authors' patient population; however, both overall and less-invasive cohorts had lower requirements for other blood components with E-aminocaproic acid. There was no association with major Society of thoracic surgeons (STS)-defined morbidity and mortality in both groups., Competing Interests: Conflict of Interest Dr. Gillinov is a consultant for Edwards Lifesciences, Medtronic, Abbott, CryoLife, AtriCure, and ClearFlow. Other authors have no disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hemoptysis is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Antifibrinolytic agents have shown efficacy in a broad range of bleeding disorders and conditions., Objectives: The goal of this study was to examine the use of antifibrinolytic agents in managing hemoptysis in CF. We developed a clinical treatment pathway for inpatient and outpatient use, and rates of admission for bleeding prior to and following implementation of the pathway are reported., Methods: All adult patients with CF treated with systemic antifibrinolytic agents over a 54-month period according to the treatment pathway were analyzed. Data collected included demographic characteristics, baseline CF-related characteristics, and bleeding and treatment parameters. Effectiveness of the pathway was evaluated via comparison of annualized hemoptysis admission rates prior to and following pathway enrollment., Results: Seventy-two distinct episodes of hemoptysis treated with antifibrinolytic agents were analyzed in a total of 21 adult patients with CF. Two-thirds of episodes treated involved moderate or massive hemoptysis. Bleeding ceased following a median of 2 days. Outpatient treatment was associated with a 50% reduction in the annualized hemoptysis admission rate following pathway enrollment (2.44 vs 1.23 admissions per year; P = .0024) that was independent of other changes in management. Antifibrinolytic therapy was well tolerated. One central catheter-associated upper extremity DVT was observed in a patient with previous thrombosis in the same vessel., Conclusions: A pathway using systemic antifibrinolytic therapy to treat hemoptysis in patients with CF was associated with a reduction in hospital admissions. No serious adverse events were observed. Additional studies are needed to further define the benefits of systemic antifibrinolytic use in patients with CF., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

ε-Aminocaproic acid is routinely used in cardiac surgery to prevent excess bleeding. It is rarely associated with thrombotic events. This case report illustrates the formation of intracardiac thrombi leading to massive pulmonary embolism during a coronary artery bypass graft surgery, secondary to the administration of ε-aminocaproic acid as confirmed by intraoperative transesophageal echocardiogram. After a failure of resolution with high-dose heparin, tissue plasminogen activator was used to successfully reverse the patient's hypercoagulable state.

Background: To assess the effectiveness and safety of intravenous aminocaproic acid for blood management after total knee and hip arthroplasty., Methods: Electronic databases: PubMed (1950.1-2018.8), EMBASE (1974.1-2018.8), the Cochrane Central Register of Controlled Trials (CENTRAL, 2017.10), Web of Science (1950.1-2018.8), and CNKI (1980.1-2018.8) were systematically searched for clinical controlled trials comparing intravenous aminocaproic acid and placebo after joint arthroplasties. Heterogeneity was assessed using the chi-square test and I-square statistic. The meta-analysis was performed using STATA 12.0 (College Station, TX)., Results: Six studies with 756 patients were included. Our meta-analysis revealed that there were significant differences between aminocaproic acid and placebo in terms of total blood loss (SMD = -0.673, 95% CI: -0.825 to -0.520, P <.001), hemoglobin reduction (SMD = -0.689, 95% CI: -0.961 to -0.418, P <.001), drain output (SMD = -2.162, 95% CI: -2.678 to -1.646, P <.001) and transfusion rates (RD = -0.210, 95% CI: -0.280 to -0.141, P <.001)., Conclusion: Aminocaproic acid results in a significant reduction of total blood loss, postoperative hemoglobin decline and transfusion requirement in patients undergoing arthroplasties. Due to the limited quality of the evidence currently available, the results of our meta-analysis should be treated with caution.

The purpose of this study was to determine if a higher dosing of ε-aminocaproic acid (EACA) is associated with less perioperative blood loss than a lower dose. A total of 74 patients having scoliosis surgery were analyzed. Of the 74 patients, 36 patients received EACA (10 mg/kg/h) and 38 patients received EACA (33 mg/kg/h). After controlling for key variables, an infusion of 33 mg/kg/h of EACA was associated with an increase in intraoperative blood loss of 8.1 ml/kg compared with an infusion of 10 mg/kg/h of EACA. A 33 mg/kg/h intraoperative infusion is associated with higher intraoperative blood loss than an infusion at 10 mg/kg/h.

Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.

Objective: This meta-analysis aimed to evaluate the safety and efficacy of aminocaproic acid in total knee arthroplasty (TKA) and total hip arthroplasty (THA)., Methods: The electronic databases include PubMed, Medline, Embase, Web of Science and the Cochrane Library from inception to January, 2018. Two reviewers abstracted total blood loss, hemoglobin drop, transfusion requirements, and postoperative complications. Data were using fixed-effects or random-effects models with weighted mean differences and risk difference for continuous and dichotomous variables, respectively. STATA 14.0 was used to perform the meta-analysis., Results: Six studies encompassing 756 participants were retrieved for this meta-analysis. Our study indicated that intravenous aminocaproic acid was associated with a significantly reduction in total blood loss, hemoglobin drop and need for transfusion. Additionally, no increased risk of thromboembolic events were identified., Conclusion: Based on the present meta-analysis, intravenous aminocaproic acid is effective and safe in total knee and hip arthroplasty without increasing the incidence of thromboembolic events. Further studies should focus on the comparison of aminocaproic acid and TXA in arthroplasties., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Alveolar osteitis (AO), also known as “dry socket”, is relatively common post-extraction complication. It probably occurs due to excessive fibrinolytic activity in the coagulum and is characterized by intense pain sensations. The aim of this clinical study was to examine the role of hyaluronic acid and aminocaproic acid in the treatment of AO., Methods: The study included 60 patients with the clinical diagnosis of AO. All the patients were divided into two groups of 30 patients each according to the applied non-pharmacological measure: irrigation – irrigation of dry socket with sterile saline; curettage – careful curettage. Both of these groups were further divided into three subgroups regarding the applied treatment (hyaluronic acid; hyaluronic acid + aminocaproic acid; Alvogyl ®, an anesthetic and antiseptic paste), each with 10 patients, according to the following protocol: 0.2 mL of hyaluronic acid in the form of a 0.8% gel; 2 mL of aminocaproic acid and hyaluronic acid; Alvogyl®. During each visit, scheduled for every two days until complete absence of painful sensations, the patients had the therapeutic method repeated as at the first examination. At each control visit the number of present symptoms and signs of AO was recorded, as well as the level of pain (measured with a visual analogue scale)., Results: With the use of hyaluronic acid, with or without aminocaproic one, a statistically significantly faster reduction in pain sensations was achieved, along with the reduction in the number of symptoms and signs of AO compared to the use of Alvogyl®., Conclusion: Hyaluronic acid, applied alone or in combination with aminocaproic acid significantly reduces pain sensation, thus it can be successfully used in the treatment of AO.

Purpose: To present the results of a prospective single-center study that evaluated the safety and efficacy of a hemostatic dressing following femoral artery access., Methods: Within a 9-month period, 80 patients (mean age 68±14 years; 55 men) were treated with a hemostatic dressing patch (Hematrix Active Patch) containing aminocaproic acid, calcium chloride, and thrombin after endovascular procedures via a 6- to 8-F femoral artery access. After removing the sheath, the wound dressing was placed on the puncture site followed by constant manual compression adapted to the sheath size (specified pressure times: 8 minutes for 6-F, 9 minutes for 7-F, and 10 minutes for 8-F). Patients were treated with an additional pressure bandage for 24 hours. Hemostasis was checked clinically and with duplex ultrasound after patch removal and at 24 hours. Patient characteristics [platelets, systolic blood pressure, international normalized ratio (INR), and partial thromboplastin time (PTT)], sheath sizes, and approach direction were compared among patients with successful hemostasis (within specified pressure times) vs those with prolonged compression., Results: A total of 39 6-F, 19 7-F, and 22 8-F sheaths were employed. In 73 (91.2%) of 80 patients, hemostasis was reached within the prespecified pressure times (mean 8.8±0.8 minutes). In 7 patients (4 6-F, 1 7-F, 2 8-F) a longer compression time was necessary (mean 34±30 minutes). No serious major complication occurred. Twelve (15.0%) minor and 5 (6.3%) moderate subcutaneous hematomas were observed. Two (2.5%) false aneurysms were treated successfully. Ambulation and discharge was possible within 24 hours in 79 (98.7%) cases. Patients with initial hemostasis and those with prolonged compression did not differ substantially (p>0.05) according to sheath size, approach direction, INR (1.09±0.3 vs 1.11±0.3), platelets (234±47×10(3)/µL vs 249±93×10(3)/µL), systolic blood pressure (150±26 vs 152±17 mm Hg), or PTT (31±7.9 vs 34.8±10.0 seconds)., Conclusion: The evaluated wound dressing seems to be safe and effective in reducing time to hemostasis in large arterial access sites. However, a randomized trial with a larger population and an active control group is necessary to confirm these preliminary data. Moreover, additional focus on shortening the time to ambulation is required in future studies., (© The Author(s) 2016.)

Objectives: To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined., Design: Retrospective, observational, cohort study design., Setting: Single-center, university hospital., Participants: The study included 708 adult liver transplantations performed from 2008 to 2013., Interventions: None., Measurements and Main Results: EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group., Conclusions: The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Excessive postoperative blood loss after cardiopulmonary bypass is a common problem, especially in patients suffering from congenital heart diseases. The efficacy of epsilon aminocaproic acid (EACA) as a prophylactic treatment for postoperative bleeding after pediatric open-heart surgery has not been determined. This meta-analysis investigates the efficacy of EACA in the minimization of bleeding and blood transfusion and the maintenance of coagulation tests after pediatric open-heart surgery., Methods: A comprehensive literature search was performed to identify all randomized clinical trials on the subject. PubMed, Embase, the Cochrane Library, and the Chinese Medical Journal Network were screened. The primary outcome used for the analysis was postoperative blood loss. Secondary outcomes included postoperative blood transfusion, re-exploration rate and postoperative coagulation tests. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were used as summary statistics., Results: Five trials were included in this meta-analysis of 515 patients. Prophylactic EACA was associated with a reduction in postoperative blood loss, but this difference did not reach statistical significance (MD: -7.08; 95% CI: -16.11 to 1.95; P = 0.12). Patients treated with EACA received fewer postoperative blood transfusions, including packed red blood cells (MD: -8.36; 95% CI: -12.63 to -4.09; P = 0.0001), fresh frozen plasma (MD: -3.85; 95% CI: -5.63 to -2.08; P < 0.0001), and platelet concentrate (MD: -10.66; 95% CI: -18.45 to -2.87; P = 0.007), and had a lower re-exploration rate (RR: 0.46; 95% CI: 0.23 to 0.92; P = 0.03). Prophylactic EACA also improved coagulation tests 6 hours after open-heart surgery., Conclusions: Prophylactic EACA minimizes postoperative blood transfusion and helps maintain coagulation in pediatric patients undergoing open-heart surgery. Therefore, the results of this study indicate that adjunctive EACA is a good choice for the prevention of postoperative blood transfusion following pediatric cardiac surgery.

Background: Blood conservation is a major concern in the management of surgical patients because of transfusion-related complications, limited supply, and health care costs. Tranexamic acid (TXA) and ϵ-aminocaproic acid (ϵACA) are lysine analogue antifibrinolytics used to reduce surgical bleeding and transfusions., Objective: To evaluate the efficacy and safety of TXA compared with ϵACA in the management of cardiovascular surgical bleeding at an academic medical center., Methods: This single-center, retrospective, observational cohort study included 120 patients undergoing cardiovascular surgery with or without cardiopulmonary bypass, who received at least 1 dose of perioperative TXA or ϵACA. The efficacy outcome-massive perioperative bleeding-was a composite end point of chest tube drainage >1500 mL in any 8-hour period after surgery, perioperative transfusion of 10 or more units of packed red blood cells, reoperation for bleeding, or death from hemorrhage within 30 days. The safety outcomes were incidence of thromboembolic events, postoperative renal dysfunction, seizure, and 30-day all-cause mortality., Results: The primary end point-massive perioperative bleeding-occurred in 10 patients (16.7%) in the TXA group compared with 5 patients (8.3%) in the ϵACA group (P = 0.17). There were no significant differences in the secondary end points of 30-day all-cause mortality, thromboembolic events, renal dysfunction, and seizure., Conclusions: There were no differences in the efficacy and safety outcomes between TXA and ϵACA in the management of cardiovascular surgical bleeding at our institution. Considering the substantial cost difference and comparable efficacy and safety, ϵACA may have better value over TXA for reducing cardiovascular surgical bleeding., (© The Author(s) 2014.)

Objective: To evaluate the efficacy and safety of tranexamic acid (TXA) versus epsilon aminocaproic acid (EACA) in patients undergoing thoracic aortic surgery., Design: A prospective randomized study., Setting: A tertiary care center., Participant: The study was conducted on 64 consecutive adult patients undergoing thoracic aortic surgery with cardiopulmonary bypass (CPB)., Interventions: Group EACA received a bolus of 50 mg/kg of EACA after induction of anesthesia over 20 minutes followed by maintenance infusion of 25 mg/kg/h until chest closure. Group TXA received a bolus of 10 mg/kg of TXA after induction of anesthesia over 20 minutes followed by maintenance infusion of 1 mg/kg/h until chest closure., Measurements and Main Results: Cumulated mean blood loss, total packed red blood cells, and blood product requirement up to 24 h postoperatively were comparable between groups. A significant renal injury (EACA 40% v TXA 16%; p = 0.04) and increased tendency for renal failure (EACA 10% v TXA 0%, p = 0.11; relative risk 2.15) were observed with EACA compared to TXA. There was increased tendency of seizure with TXA (EACA v TXA: 3.3% v 10%; p>0.05, relative risk 1.53). There was significant increase in the D-dimer from preoperative to postoperative values in Group EACA. (p< 0.01)., Conclusions: Both EACA and TXA were equally effective in reducing the perioperative blood loss and transfusion requirement in patients undergoing thoracic aortic surgery. While significant renal injury was observed with EACA, there was a tendency for higher incidence of seizure with TXA. Prospective placebo-controlled trials recruiting larger sample size using sensitive biomarkers are required before any recommendations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Antifibrinolytic drugs have become almost ubiquitous in their use during major surgery when bleeding is expected or commonplace. Inhibition of the fibrinolytic pathway after tissue injury has been consistently shown to reduce postoperative or traumatic bleeding. There is also some evidence for a reduction of perioperative blood transfusion. However, evidence of complications associated with exaggerated thrombosis also exists, although this appears to be influenced by the choice of the individual agent and the dose administered. There is controversy over the use of the serine protease inhibitor aprotinin, whose license was recently withdrawn but may shortly become available on the market again. In the UK, tranexamic acid, a tissue plasminogen and plasmin inhibitor, is most commonly used, with evidence for benefit in cardiac, orthopaedic, urological, gynaecological, and obstetric surgery. In the USA, ε-aminocaproic acid, which also inhibits plasmin, is commonly used. We have reviewed the current literature for this increasingly popular class of drugs to support clinical judgement in daily anaesthetic practice.

More than 30 years ago the pioneering work of Andrew and co-workers showed that the coagulation system of children is different than from adult. They have introduced the term of "developmental hemostasis" to describe this phenomenon. They were able to show that the concentration of coagulation factors and inhibitors are age-dependent and therefore reference limits from adult practice cannot be transferred to children one to one. Numerous studies showed that the perioperative loss of blood, and thus the use of homologous blood could be limited by administering antifibrinolytic substances such as aprotinin. Other antifibrinolytics acting substances like Epsilon-aminocaproic acid (EACA) or tranexamic acid (TXA) tended to be misfits in routine clinical practice. In 2006, the publication of a retrospective study carried out by Mangano et al, in which considerable safety concerns were expressed with regard to aprotinin led to a significant rethinking of its clinical use. Two years later the results of the BART (Blood Conservation using antifibrinolytics in a Randomized Trial) study confirmed that there was an increased postoperative mortality associated with the use of aprotinin compared to TXA and EACA. In a few adult studies so far tranexamic acid was found to be comparably as effective as aprotinin. Although TXA is a long known drug available on the market for more than 50 years, the studies connecting factors of indication, dosage regimen and safety are limited especially in children and infants. This article highlights the differences in the coagulation system in children compared to adult as well as indication, dosage regimens and possible side effects of antifibrinolytic agents in children., (© Georg Thieme Verlag Stuttgart · New York.)

Cardiac surgery exerts a significant strain on the blood bank services and is a model example in which a multi-modal blood-conservation strategy is recommended. Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis is one of the important contributors to increased bleeding. This knowledge has led to the use of anti-fibrinolytic agents especially in procedures performed under cardiopulmonary bypass. Nothing has been more controversial in recent times than the aprotinin controversy. Since the withdrawal of aprotinin from the world market, the choice of antifibrinolytic agents has been limited to lysine analogues either tranexamic acid (TA) or epsilon amino caproic acid (EACA). While proponents of aprotinin still argue against its non-availability. Health Canada has approved its use, albeit under very strict regulations. Antifibrinolytic agents are not without side effects and act like double-edged swords, the stronger the anti-fibrinolytic activity, the more serious the side effects. Aprotinin is the strongest in reducing blood loss, blood transfusion, and possibly, return to the operating room after cardiac surgery. EACA is the least effective, while TA is somewhere in between. Additionally, aprotinin has been implicated in increased mortality and maximum side effects. TA has been shown to increase seizure activity, whereas, EACA seems to have the least side effects. Apparently, these agents do not differentiate between pathological and physiological fibrinolysis and prevent all forms of fibrinolysis leading to possible thrombotic side effects. It would seem prudent to select the right agent knowing its risk-benefit profile for a given patient, under the given circumstances.

Objective: The purpose of this study was to compare 2 different doses of ε-aminocaproic acid (EACA) and assess their relative efficacy and safety in children undergoing corrective surgery for tetralogy of Fallot (TOF)., Design: A prospective, randomized, controlled study., Setting: A tertiary care center., Participants: One hundred twenty children undergoing corrective surgery for TOF using cardiopulmonary bypass (CPB)., Interventions: Group 1 received 100 mg/kg of EACA after induction, upon initiation of CPB, and after protamine. Group 2 received 75 mg/kg of EACA after induction, followed by a maintenance infusion of 75 mg/kg/h until chest closure, and an additional 75 mg/kg upon initiation of CPB. Group 3 did not receive any antifibrinolytic agent or placebo., Measurement and Main Results: Cumulative mean blood loss, total packed red blood cells, and fresh frozen plasma requirements were significantly less in group 2 (p ≤ 0.01). There were no significant differences in the total platelet concentrate transfused, re-exploration rate, incidence of renal failure, arrhythmias, neurologic complications, mortality, or length of intensive care unit stay among the 3 groups. The incidences of perioperative ST/T changes and chest closure time were significantly less in group 1 and group 2 (p ≤ 0.01). The duration of mechanical ventilation was significantly less in group 2 (p ≤ 0.01)., Conclusions: EACA was effective in reducing the postoperative blood loss and transfusion requirements in children undergoing corrective cardiac surgery on CPB for TOF. The dose regimen of 75 mg/kg after induction, followed by a maintenance infusion of 75 mg/kg/h until chest closure, and an additional 75 mg/kg upon initiation of CPB were more effective., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: To compare the effect of aprotinin with the effect of lysine analogues (tranexamic acid and ε-aminocaproic acid) on early mortality in three subgroups of patients: low, intermediate and high risk of cardiac surgery., Methods and Findings: We performed a meta-analysis of randomised controlled trials and observational with the following data sources: Medline, Cochrane Library, and reference lists of identified articles. The primary outcome measure was early (in-hospital/30-day) mortality. The secondary outcome measures were any transfusion of packed red blood cells within 24 hours after surgery, any re-operation for bleeding or massive bleeding, and acute renal dysfunction or failure within the selected cited publications, respectively. Out of 328 search results, 31 studies (15 trials and 16 observational studies) included 33,501 patients. Early mortality was significantly increased after aprotinin vs. lysine analogues with a pooled risk ratio (95% CI) of 1.58 (1.13-2.21), p<0.001 in the low (n = 14,297) and in the intermediate risk subgroup (1.42 (1.09-1.84), p<0.001; n = 14,427), respectively. Contrarily, in the subgroup of high risk patients (n = 4,777), the risk for mortality did not differ significantly between aprotinin and lysine analogues (1.03 (0.67-1.58), p = 0.90)., Conclusion: Aprotinin may be associated with an increased risk of mortality in low and intermediate risk cardiac surgery, but presumably may has no effect on early mortality in a subgroup of high risk cardiac surgery compared to lysine analogues. Thus, decisions to re-license aprotinin in lower risk patients should critically be debated. In contrast, aprotinin might probably be beneficial in high risk cardiac surgery as it reduces risk of transfusion and bleeding complications.

Antifibrinolytic drugs are widely used to reduce blood loss during surgery. One serious adverse effect of these drugs is convulsive seizures; however, the mechanisms underlying such seizures remain poorly understood. The antifibrinolytic drugs tranexamic acid (TXA) and ε-aminocaproic acid (EACA) are structurally similar to the inhibitory neurotransmitter glycine. Since reduced function of glycine receptors causes seizures, we hypothesized that TXA and EACA inhibit the activity of glycine receptors. Here we demonstrate that TXA and EACA are competitive antagonists of glycine receptors in mice. We also showed that the general anesthetic isoflurane, and to a lesser extent propofol, reverses TXA inhibition of glycine receptor-mediated current, suggesting that these drugs could potentially be used to treat TXA-induced seizures. Finally, we measured the concentration of TXA in the cerebrospinal fluid (CSF) of patients undergoing major cardiovascular surgery. Surprisingly, peak TXA concentration in the CSF occurred after termination of drug infusion and in one patient coincided with the onset of seizures. Collectively, these results show that concentrations of TXA equivalent to those measured in the CSF of patients inhibited glycine receptors. Furthermore, isoflurane or propofol may prevent or reverse TXA-induced seizures.

Objective: To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the suspension of aprotinin from the market in 2008 for safety reasons and its recent reintroduction in Europe and Canada., Design: Systematic review and network meta-analysis., Data Sources: A Cochrane review of antifibrinolytic treatments was chosen as the starting point for this systematic review. Medline, Embase, and the Cochrane register of trials were searched with no date restrictions for observational evidence., Study Selection: Propensity matched or adjusted observational studies with two or more of the interventions of interest (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and no treatment) that were carried out in patients undergoing cardiac surgery., Data Analysis: Network meta-analysis was used to compare treatments, and odds ratios with 95% credible intervals were estimated. Meta-analyses were carried out for randomised controlled trials alone and for randomised controlled trials with observational studies., Results: 106 randomised controlled trials and 11 observational studies (43,270 patients) were included. Based on the results from analysis of randomised controlled trials, tranexamic acid was associated on average with a reduced risk of death compared with aprotinin (odds ratio 0.64, 95% credible interval 0.41 to 0.99). When observational data were incorporated, comparisons showed an increased risk of mortality with aprotinin on average relative to tranexamic acid (odds ratio 0.71, 95% credible interval 0.50 to 0.98) and epsilon-aminocaproic acid (0.60, 0.43 to 0.87), and an increased risk of renal failure or dysfunction on average relative to all comparators: odds ratio 0.66 (95% credible interval 0.45 to 0.88) compared with no treatment, 0.66 (0.48 to 0.91) versus tranexamic acid, and 0.65 (0.45 to 0.88) versus epsilon-aminocaproic acid., Conclusion: Although meta-analyses of randomised controlled trials were largely inconclusive, inclusion of observational data suggest concerns remain about the safety of aprotinin. Tranexamic and epsilon-aminocaproic acid are effective alternatives that may be safer for patients.

Study Design: Therapeutic comparative study., Objective: To evaluate the safety and efficacy of antifibrinolytic (AF) agents in reducing blood loss and transfusions during posterior spinal fusion (PSF) in children with cerebral palsy (CP) scoliosis., Summary of Background Data: Scoliosis surgery in CP children is associated with substantial blood loss. Few reports on the role of AFs exist., Methods: A multicenter, retrospective review of a prospectively collected database of 84 consecutively enrolled patients with CF (age < 18 years) with spinal deformity who underwent PSF and instrumentation. The use of AFs, tranexamic acid (TXA), epsilon-aminocaproic acid (EACA), or none was based on the surgeon preference. Estimated blood loss (EBL), transfusion requirements, and length of stay were recorded. Analysis was performed with the independent-samples t test and 1-way analysis of variance with post hoc Bonferroni analysis., Results: The average age at the time of surgery was 14.4 ± 2.6 years. The groups were well matched in preoperative major deformity, age, levels fused, and operating time. Forty-four patients received AFs (30 TXA and 14 EACA), and 40 received no antifibrinolytics (NAF). The EBL averaged 1684 mL for the AFs group and 2685 mL for the NAF group (P = 0.002). There was more cell salvage transfusion in the NAF group. No significant differences were found in total transfusion requirements. There was a trend for decreased hospital stay in the AFs group. No adverse effects were seen. On comparison of the 3 groups (NAF, TXA, and EACA), a significant difference was observed between the TXA and the other groups with respect to EBL and cell salvage transfusion., Conclusion: AFs significantly reduced intraoperative EBL associated with PSF, with no adverse effects; however, we could not demonstrate significant differences in total transfusion, except in cell salvage. TXA was more effective than EACA in decreasing the EBL and cell salvage transfusion.

Background: ε-Aminocaproic acid (EACA) has been used to reduce the rate of cerebral aneurysm rerupture before definitive treatment. In centers administering EACA to patients with a subarachnoid hemorrhage (SAH), patients eventually diagnosed with angiographically negative subarachnoid hemorrhage (ANSAH) may also initially receive EACA, perhaps placing them at increased risk for ischemic complications., Objective: To evaluate the effect of short-term EACA on outcomes and secondary measures in patients with ANSAH., Methods: We conducted a retrospective study of 454 consecutive SAH patients over a 2-year period under a current protocol for EACA use. Patients were excluded if a source for the SAH was discovered, yielding a total of 83 ANSAH patients. The patients were assigned to groups that did or did not receive EACA. The primary end points of the study were ischemic complications, pulmonary emboli, vasospasm, ventriculoperitoneal shunting rates, and outcomes., Results: Statistical analysis yielded no significant difference between the 2 arms with respect to any of the end points: vasospasm (P = .65), deep vein thrombosis (P = .51), pulmonary embolism (P = 1.0), stroke (P = 1.0), myocardial infarction (P = 1.0), and ventriculoperitoneal shunt (P = .57). There was no statistically significant outcome difference using the modified Rankin Scale (P = .30)., Conclusion: Short-term (<72 hour) application of EACA does not result in an increase in adverse events in patients with ANSAH.

Aims: The antifibrinolytic drug tranexamic acid (TXA) improves survival after trauma. Antifibrinolytic drugs may also improve outcome after spontaneous bleeding, so we conducted a systematic review of the frequency of thrombotic events associated with their use after spontaneous bleeding, to help design future randomized controlled trials., Methods: We sought trials or observational studies of ≥20 adults involving any antifibrinolytic drug (TXA, epsilonaminocaproic acid (EACA) or aprotinin) for spontaneous (non-traumatic, non-surgical/iatrogenic), non-heamophiliac bleeding. We searched the Cochrane Central Register of Controlled Trials, OVID Medline from 1966, EMBASE from 1980, and the bibliographies of relevant articles in October 2009. We meta-analysed proportions of patients with thrombotic events, using a random effects model., Results: We found 57 studies involving 5,049 patients, 3,616 (72%) of whom had spontaneous subarachnoid haemorrhage. 3,414 (68%) patients received TXA-based treatment and 1,635 (32%) received EACA. The frequencies of limb ischaemia and myocardial infarction were <1% for TXA and EACA. The frequency of deep vein thrombosis or pulmonary embolism was 1.9% (95% confidence interval (CI) 1.1 to 2.9) for TXA and 3.0% (95% CI 1.8 to 4.6) for EACA. The occurrence of cerebral infarction was restricted to studies of subarachnoid haemorrhage when compared to other indications, both for TXA (9.7% [95% CI 5.5 to 14.8] versus 0% [95% CI 0 to 0.5]) and for EACA (7.7% [95% CI 1.8 to 17.4] versus 0% [95% CI 0 to 2.1])., Conclusions: Thrombotic events have occurred infrequently with antifibrinolytic drugs after spontaneous bleeding apart from subarachnoid haemorrhage, so further exploration of their safety and efficacy after spontaneous bleeding is justified in randomized trials.

Epsilon-aminocaproic acid (EACA) is used frequently during surgery as prophylaxis to decrease blood loss and transfusion requirements. A rare complication of EACA induced acute hyperkalemia in a patient undergoing total hip replacement is presented., (Published by Elsevier Inc.)

Objective: To assess the incidence of renal injury among pediatric patients who received aprotinin while undergoing cardiac surgery compared with those who received ε-aminocaproic acid (EACA)., Design: A retrospective observational study., Setting: A single academic center., Participants: Pediatric cardiac patients who had cardiopulmonary bypass and received aprotinin or EACA., Intervention: Patients undergoing pediatric cardiac surgery received aprotinin from 2005 to 2007 and EACA from 2008 to 2009., Measurements and Main Results: The primary outcome was acute kidney injury (AKI) defined as serum Cr elevation at discharge more than 1.5 times the baseline value. Secondary outcomes included bleeding, blood transfusion, and the volume of chest tube drainage in the first 24 hours postoperatively. One hundred seventy-eight patients met inclusion criteria; 120 patients received aprotinin, and 58 patients received EACA. These 2 groups did not differ significantly in age, weight, or duration of cardiac bypass. Logistic regression analysis, adjusted for confounding variables (ie, baseline Cr, sex, age, CPB time, inotropic support and vasopressors), showed a higher odds of suffering AKI at discharge with the usage of aprotinin (odds ratio = 4.7; 95% confidence interval, 1.1-19.5; p = 0.03). The volume of the first 24 hours of chest tube drainage was not significantly different between groups, as well as packed red blood cells and cryoprecipitate units. However, fresh frozen plasma and platelets showed statistically significant differences with more transfusion in the EACA group., Conclusion: In this retrospective study, the authors observed a higher odds of AKI for aprotinin usage compared with EACA, suggesting that the known concern for adults with adverse kidney effects with aprotinin is also appropriate for pediatric patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Tranexamic acid (TXA) and ɛ-aminocaproic acid (EACA) are used for antifibrinolytic therapy in cardiac surgery, although data directly comparing their blood sparing effect and their side effects, especially in paediatric cardiac surgical patients, are still missing., Methods: We analysed perioperative data of 234 paediatric patients weighing less than 20 kg undergoing cardiac surgery. In a 5-month period, all patients (n=114) received TXA (group TXA). During a second 5-month period, all patients (n=120) were treated with EACA (group EACA). Primary outcome was blood loss at 24h postoperatively; secondary outcome criteria were transfusion requirement, rate of revision for bleeding, postoperative complications and in-hospital mortality., Results: All descriptive and intra-operative parameters were well comparable. There was no evidence for a difference in blood loss at 24h postoperatively (TXA 21 ml kg(-1) (14-38) (median (interquartile range)) vs EACA 29 ml kg(-1) (14-40), p=0.242), rate of re-operation for bleeding (TXA 9.6% vs EACA 8.3%, p=0.725) and transfusion of blood products. The incidence of postoperative complications such as seizures (TXA 3.5% vs EACA 0.8%, p=0.203) and other neurological complications (TXA 2.6% vs EACA 1.7%, p=0.677), renal injury (TXA 9.6% vs EACA 13.3%, p=0.378), renal failure (TXA 1.8% vs EACA 4.2%, p=0.447), low cardiac output syndrome (TXA 12.3% vs EACA 10.8%, p=0.729), and vascular thrombosis (TXA 4.4% vs EACA 5.0%, p=0.824), as well as the in-hospital mortality (TXA 2.6% vs EACA 3.3%, p>0.999) did not show any statistically significant difference., Conclusions: TXA and EACA are well comparable in their effect on perioperative blood loss as well as in major clinical outcome criteria. Although the fourfold risk for seizures using TXA was not significant, we currently use EACA in paediatric cardiac surgery., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the incidence of postoperative generalized seizures in patients undergoing aortic valve replacement (AVR) under extracorporeal circulation, who received either high-dose tranexamic acid (TXA) or epsilon aminocaproic acid (EACA) as an antifibrinolytic agent., Methods: This retrospective analysis comprised 682 consecutive patients undergoing AVR with or without simultaneous coronary artery bypass surgery. Patients operated on before March 2008 were treated intra-operatively with TXA (100 mg kg⁻¹; n = 341), patients operated on after March 2008 received EACA (50 mg kg⁻¹ loading dose, followed by 25 mg kg⁻¹ h⁻¹, and an additional 5 g in the extracorporeal circuit; n = 341)., Results: Clinically diagnosed generalized seizures were observed within the first 24h postoperatively, more frequently in patients receiving TXA compared with EACA (6.4% vs 0.6%, p < 0.001, difference = 5.8%, 95% confidence interval 3.1-8.5%). Besides the antifibrinolytic agent, three other variables differed significantly between patients with and without postoperative seizures: age (mean (SD), 77.0 (5.9) years vs 73.2 (9.0) years, p = 0.039), preoperative creatinine clearance (55.4 (16.5)ml min⁻¹ vs 72.6 (28.5)ml min⁻¹, p = 0.002), and administration of recombinant activated factor VIIa (3 out of 24 patients (12.5%) vs 8 out of 658 patients (1.2%), p = 0.005). Logistic regression analysis demonstrated a significant impact of the antifibrinolytic drug, creatinine clearance, and the application of recombinant activated factor VIIa on the occurrence of generalized seizures., Conclusions: Our results indicate that high-dose TXA is associated with an increased incidence of postoperative generalized seizures in patients undergoing AVR compared with EACA, especially when suffering from renal impairment. A possible association between recombinant activated factor VIIa and the occurrence of postoperative seizures needs further investigation., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: Although the lysine analogs tranexamic acid (TXA) and aminocaproic acid (EACA) are used widely for antifibrinolytic therapy in cardiac surgery, relatively little research has been performed on their safety profiles, especially in the setting of cardiac surgery. Two antifibrinolytic protocols using either TXA or aminocaproic acid were compared according to postoperative outcome., Design: A retrospective analysis., Setting: A university-affiliated hospital., Participants: Six hundred four patients undergoing cardiac surgery., Interventions: One cohort of 275 consecutive patients received TXA; a second cohort of 329 consecutive patients was treated with EACA. Except for antifibrinolytic therapy, the anesthetic and surgical teams and their protocols remained unchanged., Measurements and Main Results: Besides major outcome criteria, namely postoperative bleeding, the need for allogeneic transfusions, operative revision because of bleeding, postoperative renal dysfunction, neurologic events, heart failure, and in-hospital mortality, the authors specifically sought differences between the groups concerning seizures. The 2 cohorts were comparable over a range of perioperative factors. Postoperative seizures occurred significantly more frequently in TXA patients (7.6% v 3.3%, p = 0.019), whereas EACA patients had a higher incidence of postoperative renal dysfunction (20.0% v 30.1%, p = 0.005). There were no differences in all other measured major outcome factors., Conclusion: Both lysine analogs are associated with significant side effects, which must be taken into account when performing risk-benefit analyses of their use. Their use should be restricted to patients at high risk for bleeding; routine use on low-risk patients undergoing standard surgeries should face renewed critical reappraisal., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose of Review: Hemorrhage, transfusions and the need for re-exploration can have a detrimental effect on patient outcome in cardiac surgery. With the suspension of aprotinin from the market, only the antifibrinolytics tranexamic acid and epsilon-aminocaproic acid (EACA) are left as pharmacological options to reduce hemostatic activation and associated bleeding complications. In light of the aprotinin story, the need for large independent safety studies has become evident. The current review will focus on the question of how far the quality of available data allows for judging these agents with regard to safety and efficacy, as well as whether or not new trails are warranted., Recent Findings: Both, tranexamic acid and EACA are effective in reducing blood loss and transfusion requirements in cardiac surgery. Analysis of data is complicated as the dosing scheme, especially for tranexamic acid, varies extremely and the agents are highly overdosed in most relevant trials. Newer data indicates that in a dose-dependent fashion, tranexamic acid is associated with an increase of adverse events, particularly the observation of seizures. In these studies, however, tranexamic acid has also been highly overdosed., Summary: The lysine analogs are unspecific enzyme inhibitors. Therefore, it is conceivable that an overdosing might reveal severe clinical side-effects beyond the inhibition of plasmin. Further studies re-evaluating the drug safety of tranexamic acid and EACA using the recommended and approved doses are necessary.

Objective: The primary aim was to compare the "clinical value" of tranexamic acid (TXA) with ε-aminocaproic acid (EACA) when used for blood conservation during high-risk cardiac surgery., Design: Data previously reported by the Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) study investigators were reanalyzed independently after appropriate statistical adjustment. The authors compared TXA with EACA for important primary and secondary outcomes and applied the "clinical value" equation to this comparison., Setting: BART, the largest blinded multicenter study on this topic to date, compared all 3 commonly used antifibrinolytics head-to-head in a randomized dose-equivalent fashion during high-risk cardiac surgery. Comparisons of TXA with EACA with application of the clinical value equation was not performed specifically by the BART investigators., Participants: One thousand five hundred fifty patients enrolled in 2 of the 3 arms of the BART study were included in the analysis (TXA, n= 770 and EACA, n = 780, with data reported by the investigators in the New England Journal of Medicine)., Main Results: The major finding was that there were no significant differences in overall safety and clinically important efficacy between TXA and EACA., Conclusions: Considering the substantial difference in costs and with the increasing volume of high-risk cardiac surgery, EACA has increased "clinical value" when compared with TXA. EACA should be the antifibrinolytic medication of choice for high-risk cardiac surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Long-term administration of the antifibrinolytic agent epsilon aminocaproic acid (EACA) reduces the rate of rehemorrhage in patients with aneurysmal subarachnoid hemorrhage (SAH), but is associated with cerebral ischemia., Objective: To evaluate short-term administration of EACA before early surgery in patients with SAH., Methods: Retrospective review of 356 patients admitted between June 2002 and December 2007 with a diagnosis of aneurysmal SAH. Medical records were reviewed to determine SAH risk factors, clinical grade at the time of admission, and incidence of rehemorrhage, permanent new-onset focal neurological deficits, computed tomography evidence of cerebral infarction, symptomatic vasospasm, and hydrocephalus., Results: Patients underwent treatment of the ruptured aneurysm an average of 47.4 hours after admission and received an average total dose of 40.6 g of EACA. The mean length of time of administration of EACA was 35.6 hours. There was a total of 5 rehemorrhages, for an overall rebleeding rate of 1.4% and a rate of rehemorrhage per 24-hour period of 0.71%. Overall, the rates of symptomatic vasospasm and permanent neurological deficits attributable to ischemic stroke were 11.5% and 7.2%, respectively, and the incidence of shunt-dependent hydrocephalus was 42.3%. Patients who were treated with coiling had higher rates of symptomatic vasospasm and ischemic complications than patients who had surgery., Conclusion: Short-term administration of EACA is associated with rates of rehemorrhage, ischemic stroke, and symptomatic vasospasm that compare favorably with historical controls. The rate of hydrocephalus is relatively high and may be attributable to EACA treatment.

Total joint arthroplasty and deformity surgery of the spine can require complex reconstructive procedures accompanied by the potential for major blood loss. In an attempt to minimize the perioperative blood loss associated with these procedures, recent focus has concentrated on the efficacy of pharmacologic agents. Antifibrinolytics such as epsilon-aminocaproic acid, tranexamic acid, and aprotinin have been shown to reduce perioperative blood loss, autologous blood donation, transfusions, and associated costs in cardiac as well as major orthopaedic surgery. These agents reduce perioperative blood loss by inhibition of clot breakdown. Prospective, randomized studies have shown that the use of these agents can be effective in reducing the perioperative blood loss and transfusion requirements in total joint arthroplasty, pediatric scoliosis surgery, and adult reconstructive surgery of the spine. Aprotinin, however, is currently under suspension from use pending further evaluation of a trial. Although concerns exist about increased thrombotic events with the use of these agents, large meta-analyses suggest that antifibrinolytics can be safely and efficaciously employed to decrease perioperative blood loss and transfusion requirements.

Antifibrinolytic agents have been prophylactically administered to patients undergoing cardiopulmonary bypass (CPB) to reduce postoperative bleeding due to plasmin-mediated coagulation disturbances. After the recent market withdrawal of aprotinin, a potent bovine-derived plasmin inhibitor, two lysine analogs, epsilon-aminocaproic acid and tranexamic acid are currently available for clinical use. Although the use of aprotinin recently raised major concerns about postoperative thrombosis and organ dysfunctions, there is a paucity of information on the potential complications related to lysine analogs. Using the available preclinical and clinical data, we present current perspectives on the hemostatic mechanism and potential harms of antifbirnolytic therapy related to cardiac surgery. Fibrin formation is the critical step for hemostasis at the site of vascular injury, and localized fibrinolytic activity counterbalances excess fibrin formation which might result in vascular occlusion. Inhibition of the endogenous fibrinolytic system may be associated with thrombotic complications in susceptible organs. It is thus important to understand CPB-related changes in endogenous fibrinolytic proteins (e.g., tissue plasminogen activator (tPA), plasminogen) and antifibrinolytic proteins (e.g., alpha(2)-antiplasmin).

Study Design: : Randomized, placebo-controlled trial., Objective: : To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery., Summary of Background Data: : Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited., Methods: : EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours after surgery. Primary end points included total allogeneic RBC transfusions through postoperative day 8 and postoperative allogeneic plus autologus RBC transfusions through postoperative day 8., Results: : Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA vs. 6.9 units placebo; P = 0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units vs. 2.8 units placebo; P = 0.03). There was no significantdifference in mean estimated intraoperative estimated-blood loss (2938 cc EACA vs. 3273 cc placebo; P = 0.32). Mean intensive care unit length of stay was decreased (EACA: 1.8 days vs. 2.8 days placebo; P = 0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs. 6.6% placebo; P = 0.15)., Conclusion: : The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a 1-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements.

Objective: Antifibrinolytic agents reduce bleeding after cardiac surgery, but there are adverse effects after their systemic use. These effects are avoided by topical application of antifibrinolytic agents in pericardial cavity. We compared the effects of topically applied epsilon-aminocaproic acid (EACA) and placebo on postoperative bleeding and transfusion requirements after coronary artery bypass surgery., Methods: In this single center prospective, randomized, double-blind trial, 53 patients were randomized into two groups to receive EACA (24 g in 250 ml of saline solution) or placebo (250 ml of saline solution) before sternal closure. Groups were comparable with respect to all preoperative and intraoperative variables. Postoperative bleeding, transfusion requirements and hematologic parameters were evaluated., Results: Postoperative bleeding within first 24 hours (h) period (EACA group 154.66+/-74.64 x Placebo group 220.21+/-136.42 ml; P=0.031) showed statistically significant inter-group difference, within 48 h (EACA group 259.14+/-420.07 x Placebo group 141.67+/-142.58 ml; P=0.614), as well as cumulative blood loss (EACA group 832.07+/-576.86 x Placebo group 827.50+/-434.12 ml; P=0.975), not showed statistically inter-group differences. Inter-group difference of blood product requirements was statistically significant (EACA group 185.90+/-342.07 x Placebo group 439.42+/-349.07 ml; P=0.016). Laboratory analyses showed no differences between the two groups postoperative (hematologic characteristics: hemoglobin (g/dl)- EACA group 9.18+/-0.92 x Placebo group 8.85+/-1.48 g/dL; P=0.11; hematocrit (%)-EACA group 28.15+/-3.35 x Placebo group 26.67+/-4.15%; P=0.06)., Conclusion: Topical use of epsilon aminocaproic acid reduces postoperative bleeding in the first 24 hours and requirements of blood transfusion after coronary artery bypass graft surgery.