Cytoprotective effect of plasmin inhibitor on necrotizing agent-induced gastric lesions in rats.
Motonobu MurakamiJung Keun YOOSanae TeramuraMasami InadaHiroshi SaitaKeiji MatsuoSigeru KusakaToru KITATakeo Miyake
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Aminocaproic acid
Antifibrinolytic
OBJECTIVE: To evaluate the literature describing topical use of tranexamic acid or aminocaproic acid for prevention of postoperative bleeding after major surgical procedures. DATA SOURCES: Literature was retrieved through MEDLINE (1946-September 2011) and International Pharmaceutical Abstracts(1970-September 2011) using the terms tranexamic acid, aminocaproic acid, antifibrinolytic, topical, and surgical. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All identified articles in English were evaluated. Clinical trials, case reports, and meta-analyses describing topical use of tranexamic acid or aminocaproic acid to prevent postoperative bleeding were included. DATA SYNTHESIS: A total of 16 publications in the setting of major surgical procedures were included; the majority of data were for tranexamic acid. For cardiac surgery, 4 trials used solutions containing tranexamic acid (1-2.5 g in 100-250 mL of 0.9% NaCl), and 1 trial assessed a solution containing aminocaproic acid (24 g in 250 mL of 0.9% NaCl). These solutions were poured into the chest cavity before sternotomy closure. For orthopedic procedures, all of the data were for topical irrigation solutions containing tranexamic acid (500 mg-3 g in 50-100 mL of 0.9% NaCl) or for intraarticular injections of tranexamic acid (250 mg to 2 g in 20-50 mL of 0.9% sodium chloride, with or without carbazochrome sodium sulfate). Overall, use of topical tranexamic acid or aminocaproic acid reduced postoperative blood loss; however, few studies reported a significant reduction in the number of packed red blood cell transfusions or units given, intensive care unit stay, or length of hospitalization. CONCLUSIONS: Topical application of tranexamic acid and aminocaproic acid to decrease postsurgical bleeding after major surgical procedures is a promising strategy. Further data are needed regarding the safety of this hemostatic approach.
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Prophylactic treatment with antifibrinolytic agents, epsilon-aminocaproic and tranexamic acid, reduces the incidence and severity of attacks in patients with hereditary angioedema. Long-term effectiveness or risk of antifibrinolytic agents has not been established. Sixteen patients needing continuous prophylaxis because of frequency and severity of attacks were treated with tranexamic acid. In four patients this treatment was ineffective and the drug was withdrawn after 2 months. A remission or reduction in the frequency or severity of attacks was observed in 12 patients treated for a period ranging from 8 to 34 months. Hepatic tests and blood fibrinolytic activity were not influenced by long-term oral treatment with tranexamic acid.
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We evaluated the efficacy of the prophylactic administration of ε-aminocaproic acid and tranexamic acid for reducing blood product requirements in orthotopic liver transplantation (OLT) in a prospective, double-blinded study performed in 132 consecutive patients. Patients were randomized to three groups and given one of three drugs prophylactically: tranexamic acid, 10 mg · kg−1 · h−1; ε-aminocaproic acid, 16 mg · kg−1 · h−1, and placebo (isotonic saline). Perioperative management was standardized. Coagulation tests, thromboelastogram, and blood requirements were recorded during OLT and in the first 24 h. There were no differences in diagnosis, Child score, or preoperative coagulation tests among groups. Administration of packed red blood cells was significantly reduced (P = 0.023) during OLT in the tranexamic acid group, but not in the ε-aminocaproic acid group. There were no differences in transfusion requirements after OLT. Thromboembolic events, reoperations, and mortality were similar in the three groups. Prophylactic administration of tranexamic acid, but not ε-aminocaproic acid, significantly reduces total packed red blood cell usage during OLT. Implications In a randomized study of 132 consecutive patients undergoing liver transplantation, we found that tranexamic acid, but not ε-aminocaproic acid, reduced intraoperative total packed red blood cell transfusion.
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Studies have shown that antifibrinolytic (aprotinin, tranexamic acid, epsilon-aminocaproic acid) reduce blood loss in orthopedic surgery. However, most lacked sufficient power to evaluate the efficacy and safety on clinical outcomes. This meta-analysis aims to evaluate whether intravenous antifibrinolytics, when compared with placebo, reduce perioperative allogeneic erythrocyte transfusion requirement in adults undergoing orthopedic surgery and whether it might increase the risk of venous thromboembolism. From MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, the authors identified 43 randomized controlled trials in total hip and knee arthroplasty, spine fusion, musculoskeletal sepsis, or tumor surgery performed to July 2005 (for aprotinin, 23 trials with 1,268 participants; tranexamic acid, 20 with 1,084; epsilon-aminocaproic acid, 4 with 171). Aprotinin and tranexamic acid reduced significantly the proportion of patients requiring allogeneic erythrocyte transfusion according to a transfusion protocol. The odds ratio was 0.43 (95% confidence interval, 0.28-0.64) for aprotinin and 0.17 (0.11-0.24) for tranexamic acid. Results suggest a dose-effect relation with tranexamic acid. Epsilon-aminocaproic acid was not efficacious. Unfortunately, data were too limited for any conclusions regarding safety. Although the results suggest that aprotinin and tranexamic acid significantly reduce allogeneic erythrocyte transfusion, further evaluation of safety is required before recommending the use of antifibrinolytics in orthopedic surgery.
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We evaluated the efficacy of the prophylactic administration of ε-aminocaproic acid and tranexamic acid for reducing blood product requirements in orthotopic liver transplantation (OLT) in a prospective, double-blinded study performed in 132 consecutive patients. Patients were randomized to three groups and given one of three drugs prophylactically: tranexamic acid, 10 mg · kg−1 · h−1; ε-aminocaproic acid, 16 mg · kg−1 · h−1, and placebo (isotonic saline). Perioperative management was standardized. Coagulation tests, thromboelastogram, and blood requirements were recorded during OLT and in the first 24 h. There were no differences in diagnosis, Child score, or preoperative coagulation tests among groups. Administration of packed red blood cells was significantly reduced (P = 0.023) during OLT in the tranexamic acid group, but not in the ε-aminocaproic acid group. There were no differences in transfusion requirements after OLT. Thromboembolic events, reoperations, and mortality were similar in the three groups. Prophylactic administration of tranexamic acid, but not ε-aminocaproic acid, significantly reduces total packed red blood cell usage during OLT. Implications In a randomized study of 132 consecutive patients undergoing liver transplantation, we found that tranexamic acid, but not ε-aminocaproic acid, reduced intraoperative total packed red blood cell transfusion.
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Background: Antifibrinolytics can reduce intraoperative blood loss. The primary aim of this study was to determine the efficacy of intraoperative tranexamic acid, epsilon-aminocaproic acid, and placebo at reducing perioperative blood loss and the transfusion rate in patients with adolescent idiopathic scoliosis undergoing posterior spinal arthrodesis. Methods: This is a prospective, randomized, double-blind comparison of tranexamic acid, epsilon-aminocaproic acid, and placebo used intraoperatively in patients with adolescent idiopathic scoliosis. One hundred and twenty-five patients with adolescent idiopathic scoliosis were randomly assigned to the tranexamic acid, epsilon-aminocaproic acid, or control groups. Parameters recorded included estimated blood loss, hematocrit, blood product usage, drain output, and total blood losses. The primary outcomes were intraoperative blood loss and postoperative drainage. Secondary outcomes were transfusion requirements and hematocrit changes both intraoperatively and postoperatively. Results: One hundred and twenty-five patients (ninety-seven female and twenty-eight male, with a mean age of fifteen years) were randomized to receive tranexamic acid (thirty-six patients), epsilon-aminocaproic acid (forty-two patients), or saline solution (forty-seven patients). The groups were similar at baseline, with one exception: the saline solution group had a higher estimated blood volume at baseline than the tranexamic acid group. Both tranexamic acid and epsilon-aminocaproic acid reduced the estimated blood loss per degree and estimated blood loss per pedicle screw. Epsilon-aminocaproic acid, but not tranexamic acid, reduced estimated blood loss and estimated blood loss per level. Tranexamic acid also reduced total blood losses compared with epsilon-aminocaproic acid or saline solution. In an analysis controlling for level, degree, and number of anchors, tranexamic acid reduced drain output and total blood losses. Tranexamic acid or epsilon-aminocaproic acid had a smaller decrease in hematocrit postoperatively. In an analysis controlling for the mean arterial pressure during surgical exposure, tranexamic acid reduced estimated blood loss and total blood losses. Overall, antifibrinolytics (tranexamic acid or epsilon-aminocaproic acid) reduced estimated blood loss, total blood losses, and the decline in hematocrit postoperatively compared with saline solution. There was no difference among the groups with respect to the transfusion rate, duration of surgery, levels fused, or pedicle screws placed. Conclusions: Tranexamic acid and epsilon-aminocaproic acid reduced operative blood loss but not transfusion rate. Tranexamic acid is more effective at reducing postoperative drainage and total blood losses compared with epsilon-aminocaproic acid. Maintenance of the mean arterial pressure at <75 mm Hg during surgical exposure appears to be critical for maximizing antifibrinolytic benefit. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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перебіг оперативних втручань у дітей можуть ускладнюватися розвиткомперіопераційної кровотечі. Застосування препаратів із антифібринолітичною дією зменшуєта превентує розвиток інтраопераційної крововтрати у дорослих та пацієнтів дитячого віку.Антифібринолітичні препарати такі, як транексамова кислота (ТКК) проявила свою ефективністьу якості зменшення обсягу періопераційної крововтрати, трансфузії у дорослих пацієнтів тадітей при травмі, кардіохірургічних та великих ортопедичних втручань. Проте використанняданого препарату у категорії пацієнтів високого ризику та у навантажувальних дозах > 100 мг/кг може асоціюватися із розвитком тромбоемболічних та судомних ускладнень. Однією із перевагзастосування амінокапронової кислоти (АКК) є її широка доступність, вартість і водночасефективність. Порівнюючи ефективність лізинових похідних у пацієнтів із краніостенозомА. Borst, C. Bonfield зазначають, що при використанні АКК в порівнянні із ТКК підвищуєтьсярівень інтраопераційної крововтрати (21 ± 13 vs. 17 ± 10), проте статистично вона не є значима.Апротинін, у якості препарату для зменшення крововтрати у кардіохірургічних пацієнтів впорівнянні із лізиновими похідними, являється більш ефективним для зниження періопераційної
крововтрати. Проте після дослідження The Blood Conservation Using Antifibrinolytics in a Random-ized Trial (BART) (Fergusson D. et al. 2008) є обмежено доступний у багатьох країнах через високу
кількість тромбоемболічних ускладнень та підвищену смертність. На даний момент активнодосліджуються протизапальні властивості не лише апротиніну, а й ТКК та АКК.
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