Anticoagulation Management and Antithrombin Supplementation Practice during Veno-venous Extracorporeal Membrane Oxygenation

Abstract

Background There is a lack of consensus on how to manage anticoagulation during veno-venous extracorporeal membrane oxygenation, including antithrombin monitoring and supplementation. The authors’ aim was to determine current practice in a large number of extracorporeal membrane oxygenation centers around the world. Methods This was an electronic survey disseminated in 2018 to directors and coordinators of extracorporeal membrane oxygenation centers as well as to extracorporeal membrane oxygenation experts. Participating centers were classified according to some covariates that may affect practice, including 2017 gross national income per capita, primary patient population, and annual extracorporeal membrane oxygenation patient volume. Results The authors analyzed 273 unique responses from 50 countries. Systemic anticoagulation was routinely prescribed in 264 (96.7%) centers, with unfractionated heparin being the drug of choice in 255 (96.6%) of them. The preferred method to monitor anticoagulation was activated partial thromboplastin time in 114 (41.8%) centers, activated clotting time in 82 (30.0%) centers, and anti-factor Xa activity in 62 (22.7%) centers. Circulating antithrombin activity was routinely monitored in 133 (48.7%) centers. Antithrombin supplementation was routinely prescribed in 104 (38.1%) centers. At multivariable analyzes, routine antithrombin supplementation was associated with national income, being less likely in lower- than in higher-income countries (odds ratio, 0.099 [95% CI, 0.022 to 0.45]; P = 0.003); with primary patient population being more frequent in mixed (odds ratio, 2.73 [1.23 to 6.0]; P = 0.013) and pediatric-only centers (odds ratio, 6.3 [2.98 to 13.2]; P < 0.001) than in adult-only centers; but not with annual volume of extracorporeal membrane oxygenation cases, being similarly common in smaller and larger centers (odds ratio, 1.00 [0.48 to 2.08]; P = 0.997). Conclusions There is large practice variation among institutions regarding anticoagulation management and antithrombin supplementation during veno-venous extracorporeal membrane oxygenation. The paucity of prospective studies and differences across institutions based on national income and primary patient population may contribute to these findings. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Anticoagulation and Antithrombin in Veno-venous Extracorporeal Membrane Oxygenation

“…In the current issue of Anesthesiology, Protti et al determined current practice in veno-venous extracorporeal membrane oxygenation by surveying 50 countries with 273 unique responses (Extracorporeal Life Support Centers). 5 Ninety-seven percent of centers prescribed heparin as the anticoagulant of choice, 5 consistent with previous publications. Although most centers use heparin for extracorporeal membrane oxygenation, bleeding, variable pharmacodynamics, 6 and patient drug resistance 6 are problematic, necessitating monitoring.…”

“…Retrospective clinical studies in extracorporeal membrane oxygenation and non-extracorporeal membrane oxygenation adults and children have demonstrated that use of an anti-Xa monitoring strategy may improve patient outcomes, including survival. 7 In this study, Protti et al 5 report that 49% of centers measured antithrombin concentration with routine supplementation in 38.1% if the target was not reached (51%), or if antithrombin was lower than 70% (49%). Not surprisingly, due to the cost of antithrombin, multivariate analyses demonstrated antithrombin supplementation was associated with national income and less likely to be prescribed in lower income countries.…”

“…6 The major challenge is identifying the "best way" to monitor heparin effect with optimal patient outcomes. 5 Laboratory monitoring of heparin was divided among centers included partial thromboplastin time (PTT), activated clotting time, and anti-factor Xa activity in 41.8%, 30.0%, and 22.7%, respectively. Notably, each test has limitations, which must be recognized by the clinician.…”

“…The financial cost of extracorporeal membrane oxygenation is significant and additional untested therapies further increase the cost (antithrombin supplementation). Management currently varies internationally, as demonstrated by Protti et al 5 with patient outcomes continually suboptimal. Limitations of this study include study design (survey where reported data is unvalidated); that only selective Extracorporeal Life Support Organization centers were included; and finally, that the data are dependent upon those centers that elected to report data.…”

Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO

“…9 10 Activated clotting time and anti-Xa activity tests are also performed. 10 When using the anti-Xa test, practical guidelines suggest a heparin therapeutic range (HTR) of 0.3 to 0.7 IU/mL. 11 12 13 However, those same guidelines are less specific about which HTR to use when monitoring UFH with the aPTT.…”