Traditional and non-traditional anticoagulation management during extracorporeal membrane oxygenation

Abstract

Unfractionated heparin (UFH) is the anticoagulant of choice during extracorporeal membrane oxygenation (ECMO) support. Despite its favorable pharmacologic properties, management of heparin anticoagulation during ECMO remains a major challenge. To date, little is known about the optimal monitoring strategy or the heparin dose offering the best safety/efficacy profile. Therefore, it remains unclear if the heparin dose should be adapted to target a specific "clotting time" [e.g., activated clotting time (ACT) or activated partial thromboplastin time (aPTT)] or a heparin concentration, measured by coagulation factor anti-Xa assay. In addition, no study has compared the relevance of modern viscoelastic coagulation tests over the single value of a clotting time or heparin concentration value. Although guidelines for anticoagulation during ECMO support have been published, the absence of evidence limits the quality of the recommendations provided, which explains the major intra-and inter-institutional variability observed. Large prospective multicenter trials are urgently needed to investigate the optimal anticoagulation management strategy during ECMO support.

Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO

“…These include various patient factors including patient age, underlying illness, duration of ECMO, heparin dose, target antithrombin activity, and risk of thrombotic or bleeding events. In addition, the selection and schedule of diagnostic tests including platelet count, antithrombin (AT), activated clotting time (ACT), activated partial thromboplastin time (aPTT), anti-factor Xa (anti-Xa), prothrombin time and international normalized ratio (PT/INR), thromboelastography (TEG®), or rotational thromboelastometry (ROTEM) must be carefully considered [18]. Achieving an appropriate balance between preventing thrombosis and the risk of bleeding is further complicated by the fact that standard diagnostic tests are only partial functional measures of hemostasis.…”

“…The aPTT test is a plasma-based assay of clot formation used to monitor UFH. Therapeutic ranges for ECMO are 60 to 80 s in the setting of standard bleeding risk versus targets of 40 to 60 s in patients at an increased bleeding risk [18,35,36]. The PTT test is performed by mixing citrated plasma with silica, a synthetic phospholipid (ellagic acid), and calcium to initiate clot formation.…”

COVID-19 and ECMO: An Unhappy Marriage of Endothelial Dysfunction and Hemostatic Derangements

“…11 Subtle laboratory value disturbances may precede critical clinical events, including intracranial hemorrhage, and viscoelastic evidence of hyperfibrinolysis may even be present in patients with numerically normal fibrinogen levels. 12 At the time of this writing, in the authors' center's admittedly small cohort of 7 COVID-19 patients requiring VV-ECMO with a combined total of 154 ECMO days, hyperfibrinolysis was detected (reference range Lysis30 >4.8% on TEG) in four individual patients, generating 11 discrete occurrences (nine of whom had Lysis30 >8). All pulsatile ECMO patients at the authors' center routinely are anticoagulated with bivalirudin, including all COVID-19 patients to date.…”

Anti-Factor Xa–Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions

“…2,3 Reasons for preference of UFH over alternatives include lower cost, availability of an antidote, and familiarity among clinical users. At present, UFH anticoagulation monitoring in ECMO patients includes four possible strategies, based on different measures and entailing different therapeutic thresholds: (1) activated clotting time (ACT) at 140 to 220 seconds 4,5 ; (2) activated partial thromboplastin time (APTT) at 40 to 80 seconds 4 or at 1.5 to 2.5 (ratio) 6 ;…”

“…(3) reaction time using viscoelastic tests (VETs) at 1.5-2.0 Â the upper limit of the normal range 5,7,8 ; and (4) antifactor Xa (anti-FXa) activity between 0.3 and 0.7 IU/mL. 6,9,10 In recent years, anticoagulation strategies based on anti-FXa have gained widespread consensus, with different studies advocating their superiority compared with other available options, and claiming better outcomes or at least a lower need for administration of allogeneic blood products. [10][11][12][13] This article attempts to outline why UFH anticoagulation management in ECMO only based on a target anti-FXa values in our opinion reflects an inappropriate approach.…”