Hemostatic efficacy of tranexamic acid and ε-aminocaproic acid in hip and knee arthroplasty:a Meta-analysis / 中国骨伤

OBJECTIVE@#To systematically evaluate the hemostatic efficacy of tranexamic acid and ε-aminocaproic acid in total hip arthroplasty (THA) and total knee arthroplasty (TKA).@*METHODS@#Randomized controlled trials (RCT) and retrospective case-control studies about tranexamic acid and ε-aminocaproic acid for the comparison of THA or TKA were searched electronically in PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP from the time of building databases to July 2020. Two investigators carried out literature screening and data extraction according to the inclusion and exclusion criteria respectively. The methodological quality of the included randomized controlled studies was evaluated through the Cochrane Handbook, and the methodological quality of the included retrospective case-control studies was evaluated through the NOS scale. Blood loss, the incidence of thrombosis complications, per capita input of hemoglobin were Meta-analyzed by Review Manager 5.3 software.@*RESULTS@#A total of 6 articles were included, including 4 RCTs and 2 retrospective case-control studies. A total of 3 174 patients, including 1 353 in the tranexamic acid group and 1 821 in the ε-aminocaproic acid group. Meta-analysis results showed that there were no difference statistical significance in blood loss [MD=-88.60, 95%CI(-260.30, 83.10), P=0.31], blood transfusion rate [OR=1.48, 95%CI(0.96, 2.27), P=0.08], thrombotic complications [OR=0.80, 95%CI(0.07, 8.83), P=0.85], per capita hemoglobin input [MD=0.04, 95%CI(-0.02, 0.10), P=0.18] between tranexamic acid group and ε-aminocaproic acid group during THA. While in TKA, the blood loss of the tranexamic acid group was less than that of the ε-aminocaproic acid group [MD=-147.13, 95%CI(-216.52, -77.74), P<0.0001], the difference was statistically significant. The blood transfusion rate [OR=1.30, 95%CI(0.74, 2.28), P=0.37], thrombotic complications [OR=0.95, 95%CI(0.38, 2.36), P=0.92], per capita hemoglobin input [MD=-0.00, 95%CI(-0.05, 0.06), P=0.48], tourniquet time [MD=1.54, 95%CI(-2.07, 5.14), P=0.40] were similar between two groups, the difference was not statistically significant.@*CONCLUSION@#In THA, tranexamic acid and ε-aminocaproic acid have similar hemostatic effects, while in TKA, tranexamic acid can effectively reduce the patient's blood loss and has a better hemostatic effect. Tranexamic acid is recommended as one of the first choice hemostatic drugs for TKA.

Efficacy and safety of antifibrinolytic agents in spinal surgery: a network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Significant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss and blood transfusion can create additional risks. Aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The aim of this study was to evaluate the efficacy and safety of aprotinin, EACA, and low/high doses of TXA in spinal surgery, and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method.@*METHODS@#Five electronic databases were searched, including PubMed, Cochrane Library, ScienceDirect, Embase, and Web of Science, from the inception to March 1, 2018. Trials that were randomized and compared results between TXA, EACA, and placebo were identified. The NMA was conducted with software R 3.3.2 and STATA 14.0.@*RESULTS@#Thirty randomized controlled trial (RCT) studies were analyzed. Aprotinin (standardized mean difference [SMD]=-0.65, 95% credibility intervals [CrI;-1.25, -0.06]), low-dose TXA (SMD = -0.58, 95% CrI [-0.92, -0.25]), and high-dose TXA (SMD = -0.70, 95% CrI [-1.04, -0.36]) were more effective than the respective placebos in reducing intraoperative blood loss. Low-dose TXA (SMD = -1.90, 95% CrI [-3.32, -0.48]) and high-dose TXA (SMD = -2.31, 95% CrI [-3.75, -0.87]) had less postoperative blood loss. Low-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) and high-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) significantly reduced total blood loss. However, only high-dose TXA (SMD = -2.07, 95% CrI [-3.26, -0.87]) was more effective in reducing the amount of transfusion, and was significantly superior to low-dose TXA in this regard (SMD = -1.67, 95% CrI [-3.20, -0.13]). Furthermore, aprotinin (odds ratio [OR] = 0.16, 95% CrI [0.05, 0.54]), EACA (OR = 0.46, 95% CrI [0.22, 0.97]) and high dose of TXA (OR = 0.34, 95% CrI [0.19, 0.58]) had a significant reduction in transfusion rates. Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis. Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level.@*CONCLUSIONS@#The antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery. And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.

O uso do ácido epsilon amino caproico intra-alveolar para o controle do sangramento pós-exodontia em pacientes anticoagulados / The use of epsilon amino caproic acid intraalveolar to control bleeding after extraction in anticoagulated patients

Quando pacientes em uso de anticoagulantes são submetidos a exodontias, há risco de sangramento pós-operatório. A manutenção da terapia anticoagulante tem sido indicada desde que o INR esteja dentro dos níveis terapêuticos. Recursos adicionais para o controle do sangramento, como o uso de ácido épsilon amino capróico (EACA), podem ser adotados. O objetivo deste estudo foi relatar uma série de casos de exodontias seguidas de uso intra-alveolar de EACA, em pacientes em uso de anticoagulantes com INR & # 8804; 3.0. De 25 exodontias, apenas um paciente precisou de intervenção profissional para controlar o sangramento pós-operatório. Os resultados sugerem que o uso de EACA intra-alveolar, associado aos cuidados pós-cirúrgicos de rotina, pode contribuir para a hemostasia em pacientes em uso de anticoagulantes.

When patients on anticoagulants are submitted to dental extractions, there is risk of postoperative bleeding. The maintenance of anticoagulant therapy has been indicate donce the INR is within the therapeutic levels. Additional resources for bleeding control like the use of epsilon amino caproic acid (EACA) may be adopted. The objective of this study was to report a series of cases of tooth extractions followed by the intra-alveolar use of EACA, in patients using anticoagulants with INR ≤ 3.0. From 25 tooth extractions, only one patient needed professional intervention to control postoperative bleeding. The results suggest that the use of intra-alveolar EACA, associated with routine post-surgical care, may contribute to hemostasis in patients using anticoagulants.

Antifibrinolytics in cardiac surgery.

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.

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of epsilon-Acetamidocaproic Acid in Rat Plasma

A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of epsilon-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX C18 column (150 mm x 2.0 mm, i.d., 3 microm particle size) using a mixture of 0.1% formic acid-water : acetonitrile (80 : 20, v/v) as the mobile phase at a flow rate of 200 microl/min. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of AACA were linear over the concentration range of 20~5000 ng/ml in rat plasma. The coefficient of variation and relative error at four QC levels were ranged from 1.0% to 5.8% and from -8.4% to 6.6%, respectively. The present method was successfully applied for estimating the pharmacokinetic parameters of AACA following intravenous or oral administration of ZAC to rats.

Antifibrinolítico em cirurgia cardíaca: como e quando usar? / Anfibrinolytic in cardiac surgery: how and when to use?

O sangramento pós-operatório continua sendo uma das principais complicações em cirurgia cardíaca. A etiologia desse sangramento é multifatorial, com hiperfibrinólise e disfunção plaquetária desempenhando papel fundamental Tendo em vista essas causas, as drogas antifibrinolíticas têm sido preconizadas. Desde a retirada da aprotinina do mercado, o ácido epsilon-aminocaproico e o ácido tranexâmico passaram a ser os únicos representantes disponíveis dessa classe de drogas. Essas medicações diminuem a perda de sangue e agem na resposta inflamatória associada ao procedimento cirúrgico. A eficácia variável dessas drogas ocorre devido aos vários esquemas terapêuticos e níveis séricos existentes. Recentemente têm surgido alguns questionamentos na literatura a respeito das complicações, doses, vias de administração e melhor momento para administração desses agentes...

The postoperative bleeding remains a major complication in cardiac surgery. The etiology of this bleeding is multifactorial, with hyperfibrinolysis and platelet dysfunction playing a key role. Given these causes antifibrinolytic drugs have been recommended Since the with drawal of aprotinin in the market, epsilon-aminocaproic acid and tranexamic acid became the sole representatives of this class of drugs available. These medications reduce blood loss and act on the inflammatory response associated with surgery. The variable efficacy of these drugs is due to multiple drug regimens and serum available. Recently some questions have arisen in the literature regarding the comptications, doses, routes of administration and timing for administration of these agents...

Valor del ácido épsilon aminocaproico en anestesia cardiovascular pediátrica / Value of the aminocaproic epsilon acid in pediatric cardiovascular anesthesia

El sangrado persistente luego de la circulación extracorpórea es una de las complicaciones más frecuentes en la cirugía cardiovascular e implica la administración de repetidas transfusiones de sangre, con aumento significativo de la morbilidad y la mortalidad. El enfoque terapéutico de esta complicación incluye diferentes medidas, entre las cuales el suministro de antifibrinolíticos desempeña un importante rol preventivo. Se realizó un estudio en 50 niños con operaciones cardiovasculares bajo circulación extracorpórea, realizadas en el Cardiocentro del Hospital Pediátrico William Soler durante el período comprendido entre los meses de enero de 2001 a febrero de 2002. Antes de la circulación extracorpórea se administró 100 mg/kg de ácido épsilon aminocaproico como dosis inicial durante 20 min y se mantuvo luego a razón de 15 mg/kg/h hasta el cierre de la piel. No hubo complicaciones con la administración de este agente, a pesar de que se empleó en dosis altas al inicio. No hubo sangrado prolongado ni evidencia de trastornos significativos de la coagulación, lo cual atribuimos a las medidas preventivas adoptadas(AU)

The persistent bleeding after the extracorporeal circulation is one of the most frequent complications in cardiovascular surgery and implies the administration of repeated blood transfusions with a significant increase of morbidity and mortality. The therapeutic approach of this complication includes different measures, among which the administration of antifibrinolytics plays an important preventive role. A study of 50 children that underwent cardiovascular surgery under extracorporeal circulation performed at the Heart Center of William Soler Children's Hospital from January 2001 to February 2002, was conducted. 100 mg/kg of aminocaproic epsilon acid were administered before the extracorporeal circulation as an initial dose for 20 min. It was maintained then at a rate of 15 mg/kg/h until the closure of the skin. No complications were observed, in spite of the fact that it was used at high doses at the beginning. There was neither prolonged bleeding nor evidence of marked coagulation disorders, which may be attributed to the preventive measures that were taken(AU)

Clinical investigation on the effect of intravesical instillation of antifibrinolytic agents with bacillus Calmette-Guerin on preventing bladder cancer recurrence / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of intravesical instillation of antifibrinolytic agents with bacillus Calmette-Guerin (BCG) on preventing recurrence of superficial bladder transitional cell carcinoma (BTCC) after surgical management.</p><p><b>METHODS</b>A total of 326 cases of superficial BTCC undergoing transurethral resection of bladder tumor (TURBT) or partial cystectomy were divided into 5 groups. Then the different dosage BCG with or without antifibrinolytic agents was regular instilled into bladders (once a week, then once a month after 6 times). Group A including 66 cases received intravesical instillation of 100-120 mg BCG plus 100 mg para-aminomethyl benzoic acid (PAMBA). Group B including 64 cases: instillation of 50-60 mg BCG plus 100 mg PAMBA; Group C including 65 cases: 100-120 mg BCG plus 2.0 g epsilon-aminocaproic acid (EACA); Group D including 64 cases: 50-60 mg BCG plus 2.0 g EACA; Group E (control group) including 67 cases: 100-120 mg BCG. All the cases had been followed up for 4 to 69 months (mean, 28.5 months). Not only was cystoscopy performed every 3 months, but also biopsy was carried out to identify recurrence when necessary. Side effect was recorded after instillation.</p><p><b>RESULTS</b>The rate of tumor recurrence of Group A, Group B, Group C and Group D was 12%, 10%, 9%, 9% respectively, which was significantly lower than that of Group E (30%) (chi(2) = 5.699, 6.818, 7.380, 7.867, P = 0.017, 0.009, 0.007, 0.005). And there was no significant difference of tumor recurrence rate between Group A and Group B or between Group C and Group D (Group A and Group C: high dosage BCG plus antifibrinolytic agents, while Group B and Group D: low dosage BCG plus antifibrinolytic agents) (P > 0.05). But the side effects developing in Group B and Group D after BCG instillation were less than those in Group A and Group C.</p><p><b>CONCLUSIONS</b>The efficacy of BCG on prevention the recurrence of superficial BTCC can be enhanced when combined with antifibrinolytic agents. Even if the dosage of BCG was reduced by half, the efficacy didn't changed. A new approach of low dosage BCG plus antifibrinolytic agents is recommended in the prophylaxis of recurrence of bladder cancer.</p>

Uso del ácido épsilon aminocaproico en cirugía torácica electiva / I use of the sour épsilon aminocaproico in elective thoracic surgery

Se realizó un estudio no observacional, de tipo ensayo clínico terapéutico, comparativo, prospectivo y aleatorizado a 60 pacientes a quienes se les realizó cirugía torácica electiva, con el objetivo de evaluar la eficacia del ácido épsilon aminocaproico (AEAC) en cuanto a la disminución del sangramiento posoperatorio y las transfusiones homólogas en este período, así como describir sus posibles reacciones indeseables. Se encontró que la cantidad de sangre colectada en el posoperatorio fue significativamente menor en el grupo tratado con AEAC que en el control tanto a las 6 como a las 24 horas de finalizada la intervención. Las unidades de glóbulos transfundidas en el transoperatorio fueron semejantes en los 2 grupos, pero la cantidad de glóbulos administrados en el posoperatorio resultó significativamente menor en el grupo estudio, al igual que la proporción de pacientes que necesitó transfusión homóloga en este grupo. No se hallaron diferencias entre ambos grupos en cuanto a las reacciones indeseables(AU)

A randomized, prospective and comparative clinicotherapeutic trial was conducted as part of a non-observational study that included 60 patients who underwent elective thoracic surgery in order to evaluate the effectiveness of epsilon aminocaproic acid (EACA) in connection with the decrease of postoperative bleeding and homologous transfusions in this period, as well as to describe its potential undesirable reactions. It was found that the quantity of blood collected in the postoperaive period was much lower in the group treated with EACA than in the control group, both at 6.00 and at 24.00 hrs postintervention. The units of red blood cells transfunded in the transoperative period were similar in both groups, but the quantity of red blood cells administered in the postoperative was significantly lower in the study group, as well as the proportion of patients requiring homologous transfusions in this group. There were no differences between both groups as for undesirable reactions(AU)

Epsilon aminocaproic acid in paediatric cardiac surgery to reduce postoperative blood loss.

We have studied the efficacy of epsilon aminocaproic acid in reducing postoperative blood loss in infants and children with congenital cyanotic cardiac anomalies undergoing corrective operative procedures. This prospective study was carried out on 170 infants and children randomly divided into two equal groups. Group A acted as the control group and received normal saline as placebo while group B patients received epsilon aminocaproic acid (100 mg/kg body wt) intravenously slowly soon after anaesthetic induction followed by 100 mg/kg in the cardiopulmonary bypass pump at the time of starting of cardiopulmonary bypass and 100 mg/kg after weaning from bypass over a period of 3 h. In group A the time for sternal closure after separation from bypass and administration of protamine was 75.18 +/- 5.5 min and in group B 50.7 +/- 5.2, (P < 0.001). Blood loss at 24 h in group A was 42.6 +/- 6.9 ml/kg/24 h and in group B 23.7 +/- 5.8 ml/kg/24 h, (P < 0.001). The need for packed red cells in group A was 21.8 +/- 7.1 ml/kg/24 h and in group B 10.7 +/- 7.8 ml/kg/24 h, (P < 0.001). The need for platelet concentrate in group A was 22.0 +/- 6.7 ml/kg/24 h and group B 6.2 +/- 3.2 ml/kg/24 h, (P < 0.001). Fibrin degradation products (split) in group A was 8.2 +/- 0.8 micrograms/ml, and group B 3.8 +/- 1.3 micrograms/ml, (P < 0.001). Reexploration rate was also considerably reduced in group B, 5 of 85 (6%) compared to group A, 13 of 85 (15%), (P < 0.001). It was found that epsilon aminocaproic acid is effective in reducing postoperative blood loss, packed red cells and plasma product requirements in paediatric patients undergoing corrective surgical procedures for congenital cyanotic heart diseases.

Tissue change after embedding gelatin matrix implant(ffibrel) in subcutaneous tissue of rats; histologic, immunohistochemical and scanning electron microscopic study

Analysis of Effect of Coagulation Management Based on the Changes of Thromboelastographic Variables during Orthotopic Liver Transplantation / 대한마취과학회지

Introduction: Thromboelastography (TEG) provides an overall assessment of the platelet-coagulation protein cascade interaction. The information generated from the TEG is rapidly obtained and made useful to guide replacement therapy. The purpose of this study was to evaluate the efficacy of the TEG as its guided blood replacement therapy and pharmacological therapy during liver transplantation. METHODS: This study was carried out in 13 consecutive patients who were subjected to TEG-guided replacement therapy during liver transplantation. A prepared mixture of blood products used for continuous replacement therapy was a fluid composed of red blood cells(2 units), fresh frozen plasma (2 units), and normal saline(500 ml). The pharmacological therapy was performed by comparing TEG of untreated blood and blood treated with antifibrinolytic and heparin neutralizing agent. Based on the findings of TEG, platelet concentrates were given. The TEG samples were obtained at various intervals. Additional TEG tracing was obtained as needed to see the effect of therapeutic intervention. RESULTS: In all patients the reaction time was kept in an acceptable range in the preanhepatic stage by administration of the mixture of blood products. Heparin-induced anticoagulation was observed in 3 cases in the anhepatic stage and in 11 cases upon reperfusion. Fibrinolysis was seen in all but one patients: 8% in the preanhepatic stage, 41% in the anhepatic stage, 69% at reperfusion, and 2% in the postanhepatic stage. Early and aggressive treatment with epsilon-aminocaproic acid effectively inhibited fibrinolysis without complications. Ten patients needed platelet transfusion in the postanhepatic stage with significant improvement in the TEG. CONCLUSIONS: The results of this study suggest that TEG monitoring and TEG-guided replacement and pharmacological therapy are clinically effective in maintaining blood coagulability.

Hemostasis in acquired hemophilia--role of intracavitary instillation of EACA.

An 82 year old man developed antibodies against coagulation factor VIII:C without any apparent cause. Bleeding from the soft tissue cavity could not be controlled by factor VIII:C concentrates, immunosuppression with steroids and intravenous immunoglobulin therapy in the standard dosages. However, a single injection of Epsilon Aminocaproic Acid (EACA) instilled into the cavity under aseptic precautions achieved lasting hemostasis with resultant wound healing.

The Effect of Aminocaproic Acid and Prednisolone in the Traumatic Hyphema

It is recognized that rebleeding of traumatic hyphema may predispose patients to several complications including decreased visual acuity. We reviewed the medical records of 92 patients(92 eyes) with the diagnosis of nonperforating traumatic hyphema. The relative efficiencies of Aminocaproic acid and systemic Predisolone for reducing rate of rebleeding and their side effects were evaluated under the statistical analysis. Fourty-seven patients received an oral dosage of 50 mg/kg of Aminocaproic acid every 4 hours for 5 days(up to a maximum 30 gm/day), and fourty-five patients took an oral dosage of 0.6 mg/kg of Prednisolone daily in two devided doses. The frequency of rebleeding was not statistically significantly different between the aminocaproic acid treated group(4.3%, 2/47 patients) and the prednisolone treated group(6.7%, 3/45 patients). The developing rates of their acute adverse reaction were statistically different between the aminocaproic acid treated group(44.7%, 21/47 patients) and the prednisolone treated group(20%, 9/45 patients).

A Clinical Study of Traumatic Hyphema

Traumatic hyphema accounts for about 6.7% of ocular trauma and its visual threatening associated ocular injuries are commotio retinae, retinal detachment, macular hole. cataract and rebleeding. The authors reviewed the medical records of 98 patients (98 eyes) having been admitted to the Joongang Gil Hospital between March 1989 and February 1991 with the diagnosis of nonperforating traumatic hyphema. Prospective study was performed as to the effect of epsilon-aminocaproic acid (EACA) in the clearance time of blood clot in the anterior chamber and the frequency of rebleeding. The avlrage clearance time of blood clot was significantly longer in the EACA treated group (5.8 days) than in the control group (3.5 days)(t-Test P0.05).

Aneurisma intracraniano associado com doença de moya-moya: relato de caso / Intracranial aneurysm associated with moya-moya disease: case report

Os autores relatam o caso de um paciente com doença de Moya-Moya e aneurisma duplo da artéria basilar. Discutem os aspectos etiopatogênicos, o diagnóstico e a melhor forma de tratamento

Emergencies in Hemophilia

9 classic hemophilacs in Severance Hospital, Yonsei University from Dec. '77 to Aug. '79 were reviewed and analysed and the following results were obtained. 1. Intracranial hemorrhage is required the most immediate emergent therapy in hemophiliacs and computerized transverse axial tomogarhy may be essential for the accurate and noninvasive diagnosis and for the effective emergency treatment. 2. To conserve supplies of therapeutic materials and to decrease the possibility of transmitting hepatitis and other diseases with blood products, it is desirable to reduce the amount of blood products with the use of epsilone aminocaproic acid, and epsilone aminocaproic acid may be useful in extraction and/or other non-dental injury with hemophiliacs.