A safety comparison of heparin and argatroban anticoagulation in veno-venous extracorporeal membrane oxygenation with a focus on bleeding

. 2025 Feb ; 35 (1) : 75-81. [epub] 20241007

Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic

Typ dokumentu časopisecké články, pozorovací studie, srovnávací studie

Perzistentní odkaz   https://www.medvik.cz/link/pmid39375884

Grantová podpora
FNOs/2024 Ministerstvo Zdravotnictví Ceské Republiky

BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer. STUDY DESIGN AND METHODS: An observational study was conducted in all adult veno-venous ECMO patients with COVID-19-associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45-60 s). Bleeding complications requiring transfusion and life-threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality-related bleeding. RESULTS: The total time on ECMO per patient was 16 days with an in-hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life-threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality-related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032). DISCUSSION: Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality-related bleeding.

Zobrazit více v PubMed

Martucci G, Słomka A, Lebowitz SE, et al. COVID‐19 and extracorporeal membrane oxygenation. Adv Exp Med Biol. 2021;1353:173‐195. doi:10.1007/978-3-030-85113-2_10 PubMed DOI

Burša F, Frelich M, Sklienka P, Jor O, Máca J. Long‐term outcomes of extracorporeal life support in respiratory failure. J Clin Med. 2023;12(16):5196. doi:10.3390/JCM12165196 PubMed DOI PMC

Pratt EH, Stokes JW, Fan E. Bleeding and clotting while supported with ECMO: time to move forward. Intensive Care Med. 2022;48(8):1059‐1061. doi:10.1007/S00134-022-06805-Y PubMed DOI

Nunez JI, Gosling AF, O'Gara B, et al. Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis. Intensive Care Med. 2022;48(2):213‐224. doi:10.1007/S00134-021-06593-X PubMed DOI PMC

Lv X, Deng M, Wang L, Dong Y, Chen L, Dai X. Low vs standardized dose anticoagulation regimens for extracorporeal membrane oxygenation: a meta‐analysis. PLoS One. 2021;16(4):e0249854. doi:10.1371/JOURNAL.PONE.0249854 PubMed DOI PMC

Martucci G, Giani M, Schmidt M, et al. Anticoagulation and bleeding during Veno‐venous extracorporeal membrane oxygenation: insights from the PROTECMO study. Am J Respir Crit Care Med. 2024;209(4):417‐426. doi:10.1164/RCCM.202305-0896OC PubMed DOI

Burša F, Sklienka P, Frelich M, Jor O, Ekrtová T, Máca J. Anticoagulation management during extracorporeal membrane oxygenation‐a mini‐review. Medicina (Kaunas). 2022;58(12):1783. doi:10.3390/MEDICINA58121783 PubMed DOI PMC

Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526‐2533. doi:10.1001/JAMA.2012.5669 PubMed DOI

Barbaro RP, MacLaren G, Boonstra PS, et al. Extracorporeal membrane oxygenation support in COVID‐19: an international cohort study of the extracorporeal life support organization registry. The Lancet. 2020;396(10257):1071‐1078. doi:10.1016/S0140-6736(20)32008-0 PubMed DOI PMC

Ramanathan K, Shekar K, Ling RR, et al. Extracorporeal membrane oxygenation for COVID‐19: a systematic review and meta‐analysis. Crit Care. 2021;25(1):1‐11. doi:10.1186/S13054-021-03634-1/TABLES/3 PubMed DOI PMC

Capila I, Linhardt RJ. Heparin‐protein interactions. Angew Chem Int Ed Engl. 2002;41(3):390‐412. doi:10.1002/1521-3773(20020201)41:3<390::aid-anie390>3.0.co;2-b PubMed DOI

Binari RC, Staveley BE, Johnson WA, Godavarti R, Sasisekharan R, Manoukian AS. Genetic evidence that heparin‐like glycosaminoglycans are involved in wingless signaling. Development. 1997;124(13):2623‐2632. doi:10.1242/DEV.124.13.2623 PubMed DOI

Castelli R, Porro F, Tarsia P. The heparins and cancer: review of clinical trials and biological properties. Vasc Med. 2004;9(3):205‐213. doi:10.1191/1358863X04VM566RA PubMed DOI

Levy JH, Connors JM. Heparin resistance—clinical perspectives and management strategies. N Engl J Med. 2021;385(9):826‐832. doi:10.1056/NEJMRA2104091/SUPPL_FILE/NEJMRA2104091_DISCLOSURES.PDF PubMed DOI

Hileman BA, Martucci G, Rizzitello N, et al. Antithrombin during veno‐venous extracorporeal membrane oxygenation with heparin anticoagulation: a single‐center cohort study. Perfusion. 2024;4:2676591241258048. doi:10.1177/02676591241258048 PubMed DOI PMC

Godier A, Clausse D, Meslin S, et al. Major bleeding complications in critically ill patients with COVID‐19 pneumonia. J Thromb Thrombolysis. 2021;52:18‐21. doi:10.1007/s11239-021-02403-9 PubMed DOI PMC

Lee GM, Arepally GM. Heparin‐induced thrombocytopenia. Hematology. 2013;2013(1):668‐674. doi:10.1182/ASHEDUCATION-2013.1.668 PubMed DOI PMC

Choi JH, Luc JGY, Weber MP, et al. Heparin‐induced thrombocytopenia during extracorporeal life support: incidence, management and outcomes. Ann Cardiothorac Surg. 2019;8(1):19‐31. doi:10.21037/ACS.2018.12.02 PubMed DOI PMC

Ito M, Baba M, Sato A, Pauwels R, de Clercq E, Shigeta S. Inhibitory effect of dextran sulfate and heparin on the replication of human immunodeficiency virus (HIV) in vitro. Antiviral Res. 1987;7(6):361‐367. doi:10.1016/0166-3542(87)90018-0 PubMed DOI

Mycroft‐West C, Su D, Elli S, et al. The 2019 coronavirus (SARS‐CoV‐2) surface protein (spike) S1 receptor binding domain undergoes conformational change upon heparin binding. bioRxiv. 2020;971093. doi:10.1101/2020.02.29.971093 DOI

Lee CJ, Ansell JE. Direct thrombin inhibitors. Br J Clin Pharmacol. 2011;72(4):581‐592. doi:10.1111/J.1365-2125.2011.03916.X PubMed DOI PMC

Bates SM, Weitz JI. The mechanism of action of thrombin inhibitors. J Invasive Cardiol. 2000. https://pubmed.ncbi.nlm.nih.gov/11156731/;12 Suppl F:27F‐232F. PubMed

Rougé A, Pelen F, Durand M, Schwebel C. Argatroban for an alternative anticoagulant in HIT during ECMO. J Intensive Care. 2017;5(1):1‐5. doi:10.1186/S40560-017-0235-Y PubMed DOI PMC

Walenga JM. An overview of the direct thrombin inhibitor Argatroban. Pathophysiol Haemost Thromb. 2002;32(Suppl. 3):9‐14. doi:10.1159/000069103 PubMed DOI

Dolch MEFLHR et al. Extracorporeal membrane oxygenation bridging to lung transplant complicated by heparin‐induced thrombocytopenia. Exp Clin Transplant. 2010;8(4):329‐332. PubMed

Patel K, Saraf P, Shiu D, et al. Safety profile of Argatroban vs heparin for anticoagulation in patients requiring extra corporeal membrane oxygenation (ECMO) therapy. Chest. 2015;148(4):193A. doi:10.1378/CHEST.2281355 DOI

Iba T, Levy JH, Maier CL, Connors JM, Levi M. Four years into the pandemic, managing COVID‐19 patients with acute coagulopathy: what have we learned? J Thromb Haemost. 2024;22(6):1541‐1549. doi:10.1016/J.JTHA.2024.02.013 PubMed DOI

Manzur‐Pineda K, O'Neil CF, Bornak A, et al. COVID‐19‐related thrombotic complications experience before and during delta wave. J Vasc Surg. 2022;76(5):1374‐1382.e1. doi:10.1016/J.JVS.2022.04.053 PubMed DOI PMC

Mcmichael ABV, Ryerson LM, Ratano D, et al. ELSO adult and pediatric anticoagulation guidelines. ASAIO J. 2021;2022:303‐310. doi:10.1097/MAT.0000000000001652 PubMed DOI

Rad F, Dabbagh A, Dorgalaleh A, Biswas A. The relationship between inflammatory cytokines and coagulopathy in patients with COVID‐19. J Clin Med. 2021;10(9):2020. doi:10.3390/jcm10092020 PubMed DOI PMC

Fisser C, Winkler M, Malfertheiner MV, et al. Argatroban versus heparin in patients without heparin‐induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity‐score matched study. Crit Care. 2021;25(1):160. doi:10.1186/S13054-021-03581-X PubMed DOI PMC

Cho AE, Jerguson K, Peterson J, Patel DV, Saberi AA. Cost‐effectiveness of Argatroban versus heparin anticoagulation in adult extracorporeal membrane oxygenation patients. Hosp Pharm. 2021;56(4):276‐281. doi:10.1177/0018578719890091 PubMed DOI PMC

Sattler LA, Boster JM, Ivins‐O'keefe KM, et al. Argatroban for anticoagulation in patients requiring Venovenous extracorporeal membrane oxygenation in coronavirus disease 2019. Crit Care Explor. 2021;3(9):e0530. doi:10.1097/CCE.0000000000000530 PubMed DOI PMC

Stammers AH, Tesdahl EA, Barletti S, et al. Anticoagulant use during extracorporeal membrane oxygenation using heparin and direct thrombin inhibitors in COVID‐19 and ARDS patients. J Extra Corpor Technol. 2022;54(3):223‐234. doi:10.1182/JECT-223-234 PubMed DOI PMC

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...