Terapia anticoagulante oral: complicações hemorrágicas em indivíduos submetidos à cirurgia oral menor e avaliação in vitro do efeito sobre células ósseas

Abstract

The objectives of this study were 1) to evaluate the impact of oral anticoagulant therapy on the pattern of intraoperative and postoperative bleeding in dental surgery; 2) to investigate the effects of dabigatran etexilate, a direct thrombin inhibitor, on bone cells. To fulfill objective 1, individuals undergoing oral anticoagulant therapy with vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) and individuals without anticoagulant therapy, who had indication of dental extraction were included. Dental surgery procedures were performed without interruption of anticoagulant therapy and parameters associated with hemorrhagic outcomes were evaluated. Intraoperative bleeding was evaluated by means of the measurement of the total amount of blood collected during the procedure corrected by absorbance reading and normalized by score. The results showed that the occurrence of bleeding events and the intraoperative blood loss were similar among groups and hemorrhagic episodes were not observed amongst the individuals taking DOACs. The previous history of complications in dental procedures (p=0.001) and the use of additional hemostatic measures (p=0.017) were significantly higher in the VKA group. To fulfill objective 2, experiments were conducted by means of an in vitro model in which the direct effect of anticoagulant therapy on bone cells was evaluated. An ex-vivo animal model in which cells of animals previously treated with dabigatran etexilate were differentiated was also carried out into osteoclasts. Primary cultures of mice and rats cells were differentiated into osteoclasts and osteoblasts and treated with dabigatran etexilate solution (Pradaxa® 1-6 μg/mL) and its active principle dabigatran (0.1, 0.3, 3 and 6 μg/mL). Untreated cells were used as controls and the effects of the treatment on cell viability and differentiation were evaluated. Both dabigatran etexilate and its active principle, dabigatran inhibited osteoclast differentiation and activity in vitro and in the ex-vivo model, as demonstrated by the reduction of resorption pits and cathepsin K gene and protein expression. In osteoblast cultures, dabigatran etexilate reduced the in situ alkaline phosphatase (ALP) activity, matrix mineralization and gene expression of ALP and osteocalcin. These findings indicated osteoblast inhibition. In conclusion, oral anticoagulant therapy did not result in increased bleeding outcomes in this sample, which strengthen the advocacy of the maintenance of the therapy during dental surgery. Dabigatran etexilate treatment impaired the activity and differentiation of osteoclasts and osteoblasts.