Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial.

BACKGROUND: Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants (NOACs) is a frequent problem. We investigated whether 10% tranexamic acid (TXA) mouthwash decreases post-extraction bleeding in patients treated with NOACs. METHODS AND FINDINGS: The EXTRACT-NOAC study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial. Patients were randomly assigned to 10% TXA or placebo mouthwash and were instructed to use the mouthwash once prior to dental extraction, and thereafter for 3 times a day for 3 days. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes included periprocedural, early, and delayed bleeding, and the safety outcomes included all thrombotic events. The first patient was randomized on February 9, 2018 and the last patient on March 12, 2020. Of 222 randomized patients, 218 patients were included in the full analysis set, of which 106 patients were assigned to TXA (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the TXA group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P = 0.72). There were 46 bleeds in the TXA group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P = 0.07). TXA did not reduce the rate of periprocedural bleeding (bleeding score 4 ± 1.78 versus 4 ± 1.82, P = 0.80) and early bleeding (rate ratio, 0.76; 95% CI, 0.42 to 1.37). Delayed bleeding (rate ratio, 0.32; 95% CI, 0.12 to 0.89) and bleeding after multiple extractions (rate ratio, 0.40; 95% CI, 0.20 to 0.78) were lower in the TXA group. One patient in the placebo group had a transient ischemic attack while interrupting the NOAC therapy in preparation for the dental extraction. Two of the study limitations were the premature interruption of the trial following a futility analysis and the assessment of the patients' compliance that was based on self-reported information during follow-up. CONCLUSIONS: In patients on NOACs undergoing dental extraction, TXA does not seem to reduce the rate of periprocedural or early postoperative oral bleeding compared to placebo. TXA appears to reduce delayed bleeds and postoperative oral bleeding if multiple teeth are extracted. TRIAL REGISTRATION: ClinicalTrials.gov NCT03413891 EudraCT; EudraCT number:2017-001426-17; EudraCT Public website: eudract.ema.europa.eu.

A novel fully automatic design approach of a 3D printed face specific mask: Proof of concept.

The use of high quality facemasks is indispensable in the light of the current COVID pandemic. This study proposes a fully automatic technique to design a face specific mask. Through the use of stereophotogrammetry, computer-assisted design and three-dimensional (3D) printing, we describe a protocol for manufacturing facemasks perfectly adapted to the individual face characteristics. The face specific mask was compared to a universal design of facemask and different filter container's designs were merged with the mask body. Subjective assessment of the face specific mask demonstrated tight closure at the nose, mouth and chin area, and permits the normal wearing of glasses. A screw-drive locking system is advised for easy assembly of the filter components. Automation of the process enables high volume production but still allows sufficient designer interaction to answer specific requirements. The suggested protocol can be used to provide more comfortable, effective and sustainable solution compared to a single use, standardized mask. Subsequent research on printing materials, sterilization technique and compliance with international regulations will facilitate the introduction of the face specific mask in clinical practice as well as for general use.

Local haemostatic measures after tooth removal in patients on antithrombotic therapy: a systematic review.

OBJECTIVE: The interruption of antithrombotics prior to tooth removal because of the fear of bleeding or following postoperative bleeding increases the risk of thromboembolic events. The aim of this systematic review was to investigate which local haemostatic measures can effectively prevent postoperative bleeding in patients continuing oral antithrombotics. METHODS: A systematic review was conducted by running a search in PubMed, Embase, Web of Science and Cochrane Library. Clinical randomised trials investigating bleeding and haemostatics after tooth removal in patients on antithrombotics were identified. RESULTS: In total, 15 articles were included. The investigated haemostatics included gauze pressure, tranexamic acid-soaked gauze, sponges, glue, calcium sulfate, plant extract Ankaferd Blood Stopper, epsilon-aminocaproic acid and tranexamic acid. In patients treated with vitamin K antagonists, tranexamic acid mouthwash significantly reduced bleeding compared to placebo. Further, histoacryl glue was proven better than gelatin sponges. Other studies failed to show significant differences between haemostatics, but bleeding events were low. CONCLUSIONS: Tranexamic acid seems to effectively reduce bleeding, although its superiority to other haemostatics was not proven. In view of the rapidly changing landscape of antithrombotics and the lack of standardization of bleeding outcome, adequately powered clinical studies are required to optimise postoperative management in patients on antithrombotics. CLINICAL RELEVANCE: In order to optimise postoperative management, the best haemostatics over different patient groups have to be identified and implemented in guidelines.

Pragmatic approach to manage new oral anticoagulants in patients undergoing dental extractions: a prospective case-control study.

OBJECTIVES: The aim of this study was to validate a standardized pragmatic approach to manage new oral anticoagulants (NOACs) in patients who undergo dental extractions. MATERIALS AND METHODS: This prospective case-control study in patients undergoing dental extraction included 26 patients (mean age 76 years, 57% male) treated with dabigatran, rivaroxaban, or apixaban and 26 matched controls. Regardless of timing of extraction, drug regimen, or renal function, patients were instructed to skip only the dose on the morning of the procedure. A procedural bleeding score was recorded and early and delayed bleeding was assessed at day 1 and day 7. Bleeding events were compared with a prospectively matched control group not taking any antithrombotic drug. RESULTS: There was no difference in the procedural bleeding score or in early bleeding events (5 in both groups). However, delayed bleeding occurred more frequently in anticoagulated compared to non-anticoagulated patients (7 versus none, p = 0.01). CONCLUSIONS: Skipping the morning dose of NOACs avoids excess bleeding during and early after the procedure. However, anticoagulated patients had an increased risk of delayed bleedings. Further study is needed to determine the optimal post-procedural management. CLINICAL RELEVANCE: This is the first prospective study for the management of patients on NOACs undergoing dental extraction. Our pragmatic approach, omitting only a single morning dose, can guide clinical practice. Both patients and physicians should be aware of the increased delayed bleeding risk.