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Published in: Journal of Thrombosis and Thrombolysis 3/2018

01-10-2018

The ratio of concentrations of aminocaproic acid and tranexamic acid that prevent plasmin activation of platelets does not provide equivalent inhibition of plasmatic fibrinolysis

Authors: Vance G. Nielsen, Paul M. Ford

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2018

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Abstract

Aminocaproic acid (EACA) availability has recently been decreased whereas tranexamic acid (TXA) is still available as an antifibrinolytic agent to decrease blood loss associated with procedures involving cardiopulmonary bypass (CPB) by inhibiting plasmin mediated platelet activation. Given that the clinical inclination is to substitute TXA for EACA, we sought to compare the antifibrinolytic efficacy of the two agents using the clinically accepted molar ratio of EACA:TXA (7.9:1) that prevents platelet activation in a viscoelastic based system under a variety of conditions in human plasma; 25–50% therapeutic concentration (EACA 32.5–65 µg/ml, TXA 5–10 µg/ml) in the presence of 1500–3000 IU tissue-type plasminogen activator, with 0–50% dilution of plasma with buffer. In all equipotent concentrations, TXA provided superior antifibrinolytic action compared to EACA. It is hoped that this work will serve as a rationale to further investigate these and other similar agents, especially now in a time of unpredictable unavailability of key medications needed to optimize patient care. It is also our wish that these data assist perfusionists, anesthesiologists and cardiothoracic surgeons with their consideration of using an antifibrinolytic agent when managing complex patients with hypercoagulable states (e.g., ventricular assist device explant, infective endocarditis) undergoing CPB.
Literature
1.
go back to reference Gerstein NS, Brierley JK, Windsor J, Panikkath PV, Ram H, Gelfenbeyn KM, Jinkins LJ, Nguyen LC, Gerstein WH (2017) Antifibrinolytic agents in cardiac and noncardiac surgery: a comprehensive overview and update. J Cardiothorac Vasc Anesth 31:2183–2205CrossRefPubMed Gerstein NS, Brierley JK, Windsor J, Panikkath PV, Ram H, Gelfenbeyn KM, Jinkins LJ, Nguyen LC, Gerstein WH (2017) Antifibrinolytic agents in cardiac and noncardiac surgery: a comprehensive overview and update. J Cardiothorac Vasc Anesth 31:2183–2205CrossRefPubMed
2.
go back to reference Alkjaersig N, Fletcher AP, Sherry S (1959) ε-Aminocaproic acid: an inhibitor of plasminogen activation. J Biol Chem 234:832–837PubMed Alkjaersig N, Fletcher AP, Sherry S (1959) ε-Aminocaproic acid: an inhibitor of plasminogen activation. J Biol Chem 234:832–837PubMed
3.
go back to reference Iwamoto M (1975) Plasminogen-plasmin system IX. Specific binding of tranexamic acid to plasmin. Thromb Diath Haemorrh 33:573–585CrossRefPubMed Iwamoto M (1975) Plasminogen-plasmin system IX. Specific binding of tranexamic acid to plasmin. Thromb Diath Haemorrh 33:573–585CrossRefPubMed
4.
go back to reference Lu H, Soria C, Li H, Soria J, Lijnen HR, Perrot JY, Caen JP (1991) Role of active center and lysine binding sites of plasmin in plasmin-induced platelet activation and disaggregation. Thromb Haemost 65:67–72CrossRefPubMed Lu H, Soria C, Li H, Soria J, Lijnen HR, Perrot JY, Caen JP (1991) Role of active center and lysine binding sites of plasmin in plasmin-induced platelet activation and disaggregation. Thromb Haemost 65:67–72CrossRefPubMed
5.
go back to reference Soslau G, Horrow J, Brodsky I (1991) Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol 38:113–119CrossRefPubMed Soslau G, Horrow J, Brodsky I (1991) Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol 38:113–119CrossRefPubMed
6.
go back to reference Yurka HG, Wissler RN, Zanghi CN, Liu X, Tu X, Eaton MP, Congenital Heart Surgery Research Interest Group (2010) The effective concentration of epsilon-aminocaproic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg 111:180–184CrossRefPubMed Yurka HG, Wissler RN, Zanghi CN, Liu X, Tu X, Eaton MP, Congenital Heart Surgery Research Interest Group (2010) The effective concentration of epsilon-aminocaproic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg 111:180–184CrossRefPubMed
7.
go back to reference Yee BE, Wissler RN, Zanghi CN, Feng C, Eaton MP (2013) The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg 117:767–772CrossRefPubMed Yee BE, Wissler RN, Zanghi CN, Feng C, Eaton MP (2013) The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg 117:767–772CrossRefPubMed
8.
go back to reference Nielsen VG, Cankovic L, Steenwyk BL (2007) Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the ‘therapeutic’ concentration be reconsidered? Blood Coagul Fibrinolysis 18:35–39CrossRefPubMed Nielsen VG, Cankovic L, Steenwyk BL (2007) Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the ‘therapeutic’ concentration be reconsidered? Blood Coagul Fibrinolysis 18:35–39CrossRefPubMed
9.
go back to reference Nielsen VG, Steenwyk BL, Gurley WQ (2006) Contact activation prolongs clot lysis time in human plasma: role of thrombin-activatable fibrinolysis inhibitor and Factor XIII. J Heart Lung Transplant 25:1247–1252CrossRefPubMed Nielsen VG, Steenwyk BL, Gurley WQ (2006) Contact activation prolongs clot lysis time in human plasma: role of thrombin-activatable fibrinolysis inhibitor and Factor XIII. J Heart Lung Transplant 25:1247–1252CrossRefPubMed
10.
go back to reference Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, McGuinness S, Byrne K, Chan MT, Landoni G, Wallace S, ATACAS Investigators of the ANZCA Clinical Trials Network (2017) Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med 376:136–148CrossRefPubMed Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, McGuinness S, Byrne K, Chan MT, Landoni G, Wallace S, ATACAS Investigators of the ANZCA Clinical Trials Network (2017) Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med 376:136–148CrossRefPubMed
11.
go back to reference van Diepen S, Merrill PD, Carrier M, Tardif JC, Podgoreanu M, Alexander JH, Lopes RD (2017) Association between CK-MB area under the curve and tranexamic acid utilization in patients undergoing coronary artery bypass surgery. J Thromb Thrombolysis 43:446–453CrossRefPubMed van Diepen S, Merrill PD, Carrier M, Tardif JC, Podgoreanu M, Alexander JH, Lopes RD (2017) Association between CK-MB area under the curve and tranexamic acid utilization in patients undergoing coronary artery bypass surgery. J Thromb Thrombolysis 43:446–453CrossRefPubMed
12.
go back to reference Williams B, Wehman B, Mazzeffi MA, Odonkor P, Harris RL, Kon Z, Tanaka KA (2018) Acute intracardiac thrombosis and pulmonary thromboembolism after cardiopulmonary bypass: a systematic review of reported cases. Anesth Analg 126:425–434CrossRefPubMed Williams B, Wehman B, Mazzeffi MA, Odonkor P, Harris RL, Kon Z, Tanaka KA (2018) Acute intracardiac thrombosis and pulmonary thromboembolism after cardiopulmonary bypass: a systematic review of reported cases. Anesth Analg 126:425–434CrossRefPubMed
13.
go back to reference Yu S, Khalpey ZI, Wong RK, Huynh T, Nielsen VG (2018) Complete antithrombin replacement for anticoagulation for cardiopulmonary bypass to repair severe infective mitral valve endocarditis. Blood Coagul Fibrinolysis 29:123–125CrossRefPubMed Yu S, Khalpey ZI, Wong RK, Huynh T, Nielsen VG (2018) Complete antithrombin replacement for anticoagulation for cardiopulmonary bypass to repair severe infective mitral valve endocarditis. Blood Coagul Fibrinolysis 29:123–125CrossRefPubMed
14.
go back to reference Martin K, Knorr J, Breuer T, Gertler R, Macguill M, Lange R, Tassani P, Wiesner G (2011) Seizures after open heart surgery: comparison of ε-aminocaproic acid and tranexamic acid. J Cardiothorac Vasc Anesth 25:20–25CrossRefPubMed Martin K, Knorr J, Breuer T, Gertler R, Macguill M, Lange R, Tassani P, Wiesner G (2011) Seizures after open heart surgery: comparison of ε-aminocaproic acid and tranexamic acid. J Cardiothorac Vasc Anesth 25:20–25CrossRefPubMed
15.
go back to reference Pilbrant A, Schannong M, Vessman J (1981) Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol 20:65–72CrossRefPubMed Pilbrant A, Schannong M, Vessman J (1981) Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol 20:65–72CrossRefPubMed
Metadata
Title
The ratio of concentrations of aminocaproic acid and tranexamic acid that prevent plasmin activation of platelets does not provide equivalent inhibition of plasmatic fibrinolysis
Authors
Vance G. Nielsen
Paul M. Ford
Publication date
01-10-2018
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 3/2018
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-018-1705-3

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