Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO

Abstract

During extracorporeal membrane oxygenation (ECMO), a delicate balance is required to titrate systemic anticoagulation to prevent thrombotic complications within the circuit and prevent bleeding in the patient. Despite focused efforts to achieve this balance, the frequency of both thrombotic and bleeding events remains high. Anticoagulation is complicated to manage in this population due to the complexities of the hemostatic system that are compounded by age-related developmental hemostatic changes, variable effects of the etiology of critical illness on hemostasis, and blood-circuit interaction. Lack of high-quality data to guide anticoagulation management in ECMO patients results in marked practice variability among centers. One aspect of anticoagulation therapy that is particularly challenging is the use of antithrombin (AT) supplementation for heparin resistance. This is especially controversial in the neonatal and pediatric population due to the baseline higher risk of bleeding in this cohort. The indication for AT supplementation is further compounded by the potential inaccuracy of the diagnosis of heparin resistance based on the standard laboratory parameters used to assess heparin effect. With concerns regarding the adverse impact of bleeding and thrombosis, clinicians and institutions are faced with making difficult, real-time decisions aimed at optimizing anticoagulation in this setting. In this clinically focused review, the authors discuss the complexities of anticoagulation monitoring and therapeutic intervention for patients on ECMO and examine the challenges surrounding AT supplementation given both the historical and current perspectives summarized in the literature on these topics.

ISTH DIC subcommittee communication on anticoagulation in COVID‐19

“…This phenomenon occurs because of heparin’s ability to bind to various acute‐phase plasma proteins (increased in COVID‐19), as well as macrophages and endothelial cells, 15 which are both activated in COVID‐19. Although low antithrombin levels are another potential reason for heparin resistance, moderate to severe decreased antithrombin levels are unusual in COVID‐19 patients, with most patients having plasma levels within the low‐normal range of ~80% 11,16 . However, Ranucci et al did report antithrombin levels <60% in two of 16 patients in their analysis of COVID‐19 critically ill subjects 17 .…”

EP-7041, a Factor XIa Inhibitor as a Potential Antithrombotic Strategy in Extracorporeal Membrane Oxygenation: A Brief Report

“…It is challenging to titrate systemic antithrombotic therapy to prevent clotting within the circuit, without increasing the frequency and/or severity of bleeding complications in the patient. Limited high-quality data to guide antithrombotic management in patients on ECMO result in marked practice variability among centers ( 9 ), as well as recognition of a need for alternative antithrombotic strategies ( 10 ).…”

Bleeding, Thromboembolism, and Clinical Outcomes in Venovenous Extracorporeal Membrane Oxygenation

“…Several factors may contribute to bleeding and thromboembolism in patients receiving ECMO. The interface of blood and nonbiologic circuit components causes activation of the coagulation system and the consumption and degradation of hemostatic factors ( 7 , 8 ). Underlying critical illness compounds the risks of bleeding and thromboembolism ( 7 ).…”

“…The interface of blood and nonbiologic circuit components causes activation of the coagulation system and the consumption and degradation of hemostatic factors ( 7 , 8 ). Underlying critical illness compounds the risks of bleeding and thromboembolism ( 7 ). Continuous anticoagulation during ECMO may increase the risk of bleeding ( 1 ), and prior retrospective data suggest a dose-response relationship between anticoagulation and bleeding events ( 1 , 3 ).…”