Non-invasive dentistry method for clinical determination of bleeding time: evaluation in subjects with and without direct oral anticoagulant therapy.

Assessing bleeding duration in patients on direct oral anticoagulants (DOACs) is crucial for evaluating reversal strategies, yet no standardized methods are currently available for clinical trials. We investigated a non-invasive, reproducible bleeding model based on a routine dental cleaning procedure, aiming to provide a clinically meaningful endpoint for testing DOAC antidots. We enrolled 90 subjects in this prospective observational pilot study: 49 not receiving DOACs (group 1; 30 female, 19 male; mean age: 40.7 ± 16 years) and 41 on DOACs (group 2; 22 female, 19 male; mean age: 71.3 ± 20.4 years). Mouth-rinse samples were collected before and at 5-minute intervals for up to 60 min following bleeding-on-probing assessment, periodontal staging, and dental cleaning. Red blood cell (RBC) counts in these samples were determined using a hemocytometer. Bleeding cessation was defined as an RBC count below 150 cells/µL. Reaching this threshold within 15 min was defined as the clinical endpoint (EP). In group 1, 83.7% reached the EP (group 1a (without gingivitis): 90.9%; group 1b (with gingivitis): 77.8%). In group 2, only 39% reached the EP (group 2a (without gingivitis): 60%; group 2b (with gingivitis): 32.3%; p < 0.001 vs. group 1). The most relevant comparison for future antidote trials is between group 1b (non-DOAC with gingivitis) and group 2b (DOAC with gingivitis; p < 0.001). This model offers a standardized, non-invasive, and clinically relevant approach to monitor bleeding in DOAC-treated patients. The defined clinical endpoint (≤ 150 RBC/µL after 15 min) could serve as a useful surrogate for evaluating the efficacy of temporary DOAC reversal agents.