MANAGEMENT OF DENTAL EXTRACTIONS IN PATIENTS TAKING WARFARIN AS ANTICOAGULANT TREATMENT: A SYSTEMATIC REVIEW.

OBJECTIVES: The management of patients on anticoagulation therapy is challenging. The objective of this study was to conduct a systematic review to establish the effectiveness of hemostatic interventions to prevent postoperative bleeding following dental extractions among patients taking warfarin. METHODS: A systematic review of the literature was conducted using PubMed, EMBASE and the Cochrane Central Register of Controlled Trials databases and applying relevant MeSH terms. Identified studies were screened independently by 2 reviewers using the following selection criteria: tooth extraction, patients taking warfarin as the only anticoagulant, randomized controlled trials and a hemostatic intervention. RESULTS: Six articles were included in the final review, all evaluating different interventions. Oral or local hemostatic agents were compared in 4 studies where patients continued taking warfarin before and after the procedure; in 3 studies, there were no differences between the agents in preventing postoperative bleeding and, in 1, Histoacryl glue was superior to a gelatin sponge. Two studies compared warfarin continuation with temporary discontinuation and found that continuation did not increase the risk of bleeding in patients who had an international normalized ratio (INR) within the therapeutic range. CONCLUSIONS: Patients with an INR within the therapeutic range can safely continue taking the regular dose of warfarin before dental extractions. There is no evidence to support or reject the superiority of local hemostatic agents over warfarin discontinuation.

Rac2 is required for the formation of neutrophil extracellular traps.

Neutrophils play a critical role as a first line of defense against invading pathogens. Recently, a new defense strategy of neutrophils was described, in which pathogens are trapped and killed by NETs. However, the exact underlying mechanisms leading to the formation of NETs remain elusive. Here, we explored the role of the Rac small GTPases in the formation of NETs using neutrophils that lack Rac1, Rac2, or both isoforms. Efficient NET formation was observed in WT and Rac1null neutrophils. In contrast, NET formation was markedly impaired in cells lacking Rac2 or both Rac2 and Rac1. The defect in NET formation in Rac2null cells was rescued by exogenous ROS sources, suggesting that Rac2-mediated ROS generation is required for NET formation. In addition, we assessed the role of NO in NET formation in mouse neutrophils. Blocking NO production with the NOS inhibitor L-NAME significantly reduced NET formation. Moreover, we show that Rac2null cells produce significantly less NO than Rac1null cells or their WT counterparts. Our data suggest that Rac2 is essential for NET formation via pathways involving ROS and NO.