## 4 Discussion  
The issue of post-operative bleeding is gaining importance due to the high number of patients treated with oral anticoagulants. Although DOACs are becoming widely prescribed, there is still limited evidence on the hemostatic measures which could be applied in these patients. Conversely, the management of patients treated with warfarin has been extensively explored, with the adoption of various protocols for the limitation of bleeding risks. Intra-alveolar agents appear the most effective measure for post-op bleeding prevention. In all of the studies reporting on intra-alveolar agents [17; 18; 19; 20; 21; 22; 23; 24; 29; 30; 32; 34; 35], adequate hemostasis was observed, although in most cases in the absence of a statistically significant difference with control groups. This finding agrees with the recent systematic review by [PERSON] et al. [39], as the authors concluded that no superiority could be determined for one hemostatic agent over the others. In particular, the authors highlighted that due to a high risk of bias, the certainty of the evidence was low. Moreover, no differences in terms of bleeding events and bleeding time were detected when comparing different hemostatic interventions [39]. Importantly, it should be noted that the present evidence was exclusively based on patients treated with warfarin. The application of tranexamic acid was reported in six studies, with different administration protocols [25; 26; 31; 34; 36; 38]. In all of the described cases, the application of tranexamic acid reduced the bleeding time. However, most of the studies were performed on patients treated with warfarin, and only one study [38] was performed in patients treated with DOACs. As reported in the systematic review by [PERSON] et al. [40], local application of tranexamic acid may prevent oral bleeding in patients treated with warfarin undergoing minor oral surgery or dental extractions. In fact, the authors found that tranexamic acid mouthwash reduced the bleeding rate following dental extractions by 25% if compared with the placebo, but there were no significant differences when compared with gauze compression or suture [40]. Consistent with previous literature, our study highlights a lack of evidence in patients treated with DOACs. Therefore, definitive conclusions could not be drawn either on the actual efficacy of antifibrinolytic therapy or the beneficial effects on patients treated with DOACs. PRF application was reported in two studies conducted on patients taking warfarin 24, 25 and in one study on patients treated with DOACs [37]. In all of the studies, the available evidence supported the application of PRF in limiting the bleeding complications in the early post-op period, in the absence of episodes of delayed bleeding. This finding appears in contrast with the evidence from a recent systematic review by [PERSON] et al. [41], where the authors concluded that hemorrhagic complications after dental extractions cannot be prevented with the application of PRF in patients on oral anticoagulant therapy. Moreover, no effects on pain reduction or on postoperative alveolitis development were detected in anticoagulated individuals [41]. The present study has some limitations. First, the paucity of studies evaluating patients treated with DOACs hindered the drawing of firm conclusions on this increasingly employed class of anticoagulants. Secondly, the heterogeneity in the methodologies reported in the included studies did not allow the performance of meta-analyses. Similarly, the presence of different comparative groups could also be a confounding factor. Finally, the included studies were all at moderate/high risk of bias, thus affecting reliability of the analysis. Although the superiority of one hemostatic measure above the other cannot to date be stated in patients taking oral anticoagulants, it should be noted that such measures require further investigation even in the presence of other systemic conditions affecting coagulation capacity.