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

Background The 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. Methods Patients 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. Results Forty-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. Conclusions Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury. What is new? What are the clinical implications? ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This study was included in the Japan Registry for Clinical Trials (ID jRCT1031190030). ### Funding Statement This study was supported by the Clinical Research Support Program from Niigata University Medical and Dental Hospital. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Niigata University Clinical Research Central Review Board approved the study protocol (number SP18014). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes For privacy purposes, the data that support the findings of this study are available on request from the corresponding author.