Differences in coagulation responses to vascular injury between uninterrupted dabigatran and apixaban - a clinical prospective randomized study

Abstract

AbstractBackgroundThe coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants (DOACs) has not been elucidated. Our aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients.MethodsPatients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected three times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10–15 minutes after the start of vascular punctures.ResultsForty-two patients were enrolled. The prothrombin fragment 1+2 (F1+2) level, the primary endpoint, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median: 83 pmol/L; interquartile range: 56–133 pmol/L) than in the uninterrupted apixaban recipients (median: 1 pmol/L; interquartile range: −3–19 pmol/L; P < 0.001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients.ConclusionsUnlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.Clinical perspectiveWhat is new?To the best of our knowledge, this is the first randomized clinical comparison of the effects of direct thrombin and factor Xa inhibitors on the physiological coagulation and anticoagulation system after vascular injury while direct oral anticoagulants (DOACs) serum levels were at the peak phase.Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.This study shows that physiological anticoagulation factors are consumed during vascular injury in patients receiving DOACs.What are the clinical implications?The difference in the thrombin generation response during vascular injury between uninterrupted dabigatran and apixaban may be one of the reasons for different clinical outcomes of thrombotic and hemorrhagic complications.DOACs may inhibit an excessive coagulation response by retaining physiological anticoagulation factors.