Impact of dabigatran, rivaroxaban, apixaban and edoxaban on activated clotting time: an in vitro study

Abstract

Activated clotting time (ACT) is used to monitor anticoagulation by unfractionated heparin in patients undergoing catheter ablation for atrial fibrillation regardless of the preprocedural anticoagulation. It is recommended to achieve and maintain an ACT between 300- 400 s1. To study the impact of Non Vitamin-K antagonist oral anticoagulants (NOACs) on ACT using 3 different assays. A catheter was placed in the antecubital vein from one healthy donor to ensure that the delay between the blood sampling and the experiment was always within 30 seconds. The 4 NOACs were spiked at increasing concentrations from 0 to 1000ng/mL. ACT was measured in the local laboratory (homemade ACT) or at bedside on the Hemochron Microcoagulation Systems® using ACT+or ACT-LR cartridges. ACT was prolonged in a concentration dependent way with the 4 NOACs. ACT is more sensitive to dabigatran followed by rivaroxaban, edoxaban and lastly apixaban. The results were similar in the two replicates at subtherapeutic, therapeutic and supratherapeutic peak concentrations of NOACs. The ratios between homemade ACT at 100ng/ml and 0 ng/ml were 1.8, 1.3, 1.1 and 1.0 for dabigatran, rivaroxaban, edoxaban and apixaban, respectively. At 50ng/ml, NOACs have no or minor influence on ACT+, ACT-LR and homemade ACT (ratio: 1.1-1.2). For supratherapeutic (>400 ng/ml) concentrations, ACT+is more sensitive than ACT-LR. Maintaining NOACs until catheter ablation leads to residual NOACs concentrations that may influence ACT, depending on the delay since the last intake. The current international guidelines focusing on the ACT should be adapted to the use of the different NOACs.