Abstract
Extracorporeal membrane oxygenation (ECMO) is a mechanical life support system that dates back approximately 50 years. ECMO can be performed using veno-venous, veno-arterial, or hybrid methods and can also be used for extracorporeal cardiopulmonary resuscitation. In extracorporeal circulation, due to foreign surface contact or disruption of blood flow, the coagulation system is activated, making anticoagulant use essential. Standard practice involves using unfractionated heparin as an anticoagulant, but in some cases, its use may not be feasible. In such situations, an alternative anticoagulant agent must be selected, with direct thrombin inhibitors being the most commonly used. Our study focuses on the coagulation system and anticoagulant drugs used during ECMO, with a specific emphasis on bivalirudin. The study categorizes the data into two groups: the use of bivalirudin as a primary anticoagulant and its use as a secondary anticoagulant. A total of 28 sources were reviewed. With this study, we propose that direct thrombin inhibitors can serve as alternatives when heparin use is not possible. More experience is needed to clarify their efficacy and applicability.
Keywords: ECMO, heparin, bivalirudin, heparinin indüklediği trombositopeni
References
Ekstrakorporeal Yaşam Desteği: ELSO Kırmızı Kitap Ciltli. 1st ed., ELSO, 2017:1-29. Available from: Ekstrakorporeal Yaşam Desteği: ELSO Kırmızı Kitap Ciltli. 1st ed., ELSO, 2017:1-29.
Vuylsteke A, Brodie D, Combes A, Fowles J, Peek G. ECMO in the Adult Patient. 1st ed., Cambridge: Cambridge University Press, 2017:1-24.
Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(Suppl 2):24-43.
Jaffer IH, Fredenburgh JC, Hirsh J, Weitz JI. Medical device-induced thrombosis: what causes it and how can we prevent it? J Thromb Haemost. 2015;13(Suppl 1):72-81.
Trigonis R, Smith N, Porter S, Anderson E, Jennings M, Kapoor R, et al. Efficacy of bivalirudin for therapeutic anticoagulation in COVID-19 patients requiring ECMO support. J Cardiothorac Vasc Anesth. 2022;36(2):414-418.
Tong Y, Rouzhahong J, Zhou W, Wang R, Wang Y, Ren Y, et al. Comparison of bivalirudin versus heparin in adult extracorporeal membrane oxygenation anticoagulant therapy: a retrospective case-control study. Int J Artif Organs. 2023;46(3):162-170.
Rivosecchi RM, Arakelians AR, Ryan J, Murray H, Ramanan R, Gomez H, et al. Comparison of anticoagulation strategies in patients requiring venovenous extracorporeal membrane oxygenation: heparin versus bivalirudin. Critical Care Med. 2021;49(7):1129-1136.
Diaz D, Martinez J, Bushman G, Wolowich WR. Anticoagulation strategies in COVID-19 infected patients receiving ECMO support. J Extra Corpor Technol. 2023;55(3):121-129.
Netley J, Roy J, Greenlee J, Hart S, Todt M, Statz B. Bivalirudin anticoagulation dosing protocol for extracorporeal membrane oxygenation: a retrospective review. J Extra Corpor Technol. 2018;50(3):161-166.
Uricchio MN, Ramanan R, Esper SA, Murray H, Kaczorowski DJ, D’Aloiso B, et al. Bivalirudin versus unfractionated heparin in patients with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. ASAIO J. 2023;69:107-113.
Oğuş H, Altınay AE, Hançer H, Özgür MM, Şimşek M, Menekşe Ş, et al. Anticoagulation strategy with bivalirudin plus aspirin combination during extracorporeal membrane oxygenation for COVID-19-associated acute respiratory distress syndrome. Turk Gogus Kalp Damar Cerrahisi Derg. 2024;32(1):37-45.
Ranucci M, Ballotta A, Kandil H, Isgrò G, Carlucci C, Baryshnikova E, et al. Bivalirudin-based versus conventional heparin anticoagulation for postcardiotomy extracorporeal membrane oxygenation. Crit Care. 2011;15(6):R275.
Pieri M, Agracheva N, Bonaveglio E, Greco T, De Bonis M, Covello RD, et al. Bivalirudin versus heparin as an anticoagulant during extracorporeal membrane oxygenation: a case-control study. J Cardiothorac Vasc Anesth. 2013;27(1):30-34.
Ljajikj E, Zittermann A, Morshuis M, Börgermann J, Ruiz-Cano M, Schoenbrodt M, et al. Bivalirudin anticoagulation for left ventricular assist device implantation on an extracorporeal life support system in patients with heparin-induced thrombocytopenia antibodies. Interact Cardiovasc Thorac Surg. 2017;25(6).898-904. Erratum in: Interact Cardiovasc Thorac Surg. 2017;25(4):675.
Kartika T, Mathews R, Migneco G, Bundy T, Kaempf AJ, Pfeffer M, et al. Comparison of bleeding and thrombotic outcomes in veno-venous extracorporeal membrane oxygenation: Heparin versus bivalirudin. Eur J Haematol. 2024;112(4):566-576.
Kaseer H, Soto-Arenall M, Sanghavi D, Moss J, Ratzlaff R, Pham S, et al. Heparin vs bivalirudin anticoagulation for extracorporeal membrane oxygenation. J Card Surg. 2020;35(4):779-786.
Macielak S, Burcham P, Whitson B, Abdel-Rasoul M, Rozycki A. Impact of anticoagulation strategy and agents on extracorporeal membrane oxygenation therapy. Perfusion. 2019;34(8):671-678.
Berei TJ, Lillyblad MP, Wilson KJ, Garberich RF, Hryniewicz KM. Evaluation of systemic heparin versus bivalirudin in adult patients supported by extracorporeal membrane oxygenation. ASAIO J. 2018;64(5):623-629.
Kawaji Q, Rostami S, Whitman GJR, Broderick SR, Aziz H, Cha SL. Bivalirudin and venoarterial extracorporeal membrane oxygenation for treatment of massive pulmonary embolism from heparin-ınduced thrombocytopenia with thrombosis. J Cardiothorac Vasc Anesth. 2023;37(5):777-781.
Pappalardo F, Maj G, Scandroglio A, Sampietro F, Zangrillo A, Koster A. Bioline heparin-coated ECMO with bivalirudin anticoagulation in a patient with acute heparin-induced thrombocytopenia: the immune reaction appeared to continue unabated. Perfusion. 2009;24(2):135-137.
Hanna DJ, Torbic H, Militello M, Strnad K, Krishnan S, Hohlfelder B. Evaluation of anticoagulation with bivalirudin for heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. Int J Artif Organs. 2022;45(8):688-694.
Giuliano K, Bigelow BF, Etchill EW, Velez AK, Ong CS, Choi CW, et al. Extracorporeal membrane oxygenation complications in heparin- and bivalirudin-treated patients. Crit Care Explor. 2021;3(7):e0485.
Seelhammer TG, Rowse P, Yalamuri S. Bivalirudin for maintenance anticoagulation during venovenous extracorporeal membrane oxygenation for COVID-19. J Cardiothorac Vasc Anesth. 2021;35(4):1149-1153.
Koster A, Weng Y, Böttcher W, Gromann T, Kuppe H, Hetzer R. Successful use of bivalirudin as anticoagulant for ECMO in a patient with acute HIT. Ann Thorac Surg. 2007;83(5):1865-1867.
Jyoti A, Maheshwari A, Daniel E, Motihar A, Bhathiwal RS, Sharma D. Bivalirudin in venovenous extracorporeal membrane oxygenation. J Extra Corpor Technol. 2014;46(1):94-97.
Wahl T, Stokes A, Varner C, Zeybek B, Bardia A. Alterations in pre/post oxygenator flows due to fibrin deposition in the cardiohelp system-a case report. J Extra Corpor Technol. 2022;54(3):239-241.
Koster A, Niedermeyer J, Gummert J, Renner A. Low dose bivalirudin anticoagulation for lung transplantation with extracorporeal membrane oxygenation in a patient with acute heparin-induced thrombocytopenia. Eur J Cardiothorac Surg. 2017;51(5):1009-1011.
Das S, Chakraborty U, Sarkar A, Saha A, Narayan P. Complex management of pulmonary embolism in APLA syndrome: a case study of ECMO and bivalirudin utilization. Indian J Thorac Cardiovasc Surg. 2024;40(2):254-258.
Halawi H, Harris JE, Goodarzi A, Yau S, Youssef JG, Botros M, et al. Use of bivalirudin after initial heparin management among adult patients on long-term venovenous extracorporeal support as a bridge to lung transplant: a case series. Pharmacotherapyç 2024;44(3):283-289.
Chen E, Clarke N, Huffman L, Peltz M. Transplantation in a patient on extracorporeal membrane oxygenation with infective endocarditis, pericarditis and heparin-induced thrombocytopenia. Interact Cardiovasc Thorac Surg. 2017;24(3):462-463.
Bissell BD, Gabbard T, Sheridan EA, Baz MA, Davis GA, Ather A. Evaluation of bivalirudin as the primary anticoagulant in patients receiving extracorporeal membrane oxygenation for SARS-CoV-2-associated acute respiratory failure. Ann Pharmacother. 2022;56(4):387-392.
Sheridan EA, Sekela ME, Pandya KA, Schadler A, Ather A. Comparison of bivalirudin versus unfractionated heparin for anticoagulation in adult patients on extracorporeal membrane oxygenation. ASAIO J. 1992;68(7):920-924.
McMichael ABV, Ryerson LM, Ratano D, Fan E, Faraoni D, Annich GM. 2021 ELSO adult and pediatric anticoagulation guidelines. ASAIO J. 2022;68(3):303-310.
Ma M, Liang S, Zhu J, Dai M, Jia Z, Huang H, et al. The efficacy and safety of bivalirudin versus heparin in the anticoagulation therapy of extracorporeal membrane oxygenation: a systematic review and meta-analysis. Front Pharmacol. 2022;13.771563.
Neunert C, Chitlur M, van Ommen CH. The changing landscape of anticoagulation in pediatric extracorporeal membrane oxygenation: use of the direct thrombin ınhibitors. Front Med (Lausanne). 2022;9:887199.
Hanna DJ, Torbic H, Militello M, Strnad K, Krishnan S, Hohlfelder B. Evaluation of anticoagulation with bivalirudin for heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. Int J Artif Organs. 2022;45(8):688-694.
