To the best of our knowledge, our study was first to investigate platelet reactivity of dabigatran and rivaroxaban for patients undergoing percutaneous LAAC operation. The results presented in this study indicated that dabigatran treatment could enhanced platelet aggregation and increase platelet reactivity compared with rivaroxaban. A direct association between anticoagulation strategy and DRT was found in our research and higher platelet activation markers were predominantly found in DRT patients during 3 months post anticoagulation. Thus, our data suggested that a strategy of uninterrupted rivaroxaban administration is being used routinely in patients during occluders implantation, as it had been shown to be superior in preventing peri-procedural DRT during the first three months after LAAC operation than dabigatran.
Many studies had provided potential clinical benefit of DOACs (mainly related with rivaroxaban) for post anticoagulation after LAAC operation [18, 19]. But it is still uncertain on the optimal anticoagulation strategy due to sparse clinical trials conducted to compare direct clinical efficacy and safety between different DOACs for LAAC operation. As treatment with dabigatran was shown incomplete resolution of DRT in some cases, dabigatran treatment should be administrated cautiously after a newly closure implanted. Our results showed that patients with dabigatran had higher TRAP induced platelet aggregation compared with rivaroxaban anticoagulation (62.9% vs. 59.7%, P = 0.028). At present, there was few related literature on the mechanism of dabigatran induced thrombosis for LAAC operation. The probable explanation might be that medication with dabigatran could promote platelet aggregation through the enhancement of thrombin receptor density on thrombocytes, which contribute to formation of thrombosis . The potential dabigatran enhanced platelet reactivity mainly mediated by activation of thrombin receptor peptides is the specificity of thrombin-induced platelet activation . One previous study concluded that TRAP-induced platelet aggregation was enhanced in cardiovascular patients receiving dabigatran by the increased expression profile of thrombin receptors on the surface of platelets . Meanwhile, rivaroxaban could contribute to attenuation for platelet activity and aggregation by inhibiting coagulation FXa which might increase platelet activity via Protease Activated Receptor-1 (PAR-1) [23, 24].
The thromboembolism risk under direct thrombin inhibitors (Dabigatran) treatment has been widely discussed . The elevated plasma TAT levels had been referred as an important coagulation parameter to detect a prothrombotic state . We observed evaluated concentrations of TAT under medication with dabigatran, while no significant change was found for rivaroxaban. One previous study demonstrated that dabigatran might provoke inhibition of negative feed-back mechanism related to thrombin, thrombomodulin, and protein C formation, which leads to thrombin generation . However, this thrombus formation makers rise did not lead to the incidence of DRT.
VWF has been involved in many pathological processes including coagulation and inflammation, which might facilitate the development of DRT . In the present study, administration with dabigatran displayed an increasing expression of plasma vWF. The probable reason might be that dabigatran anticoagulation was associated with inflammation, endothelial dysfunction, and oxidative stress, increased expression of angiogenic and cell adhesion molecules .
The central molecular mechanism of platelet aggregation attributes to adhesion of activated platelets on leukocytes with interaction of platelet P-selectin and P-selectin glycoprotein ligand-1 on leukocytes . Our results showed there was an increase in the expression of plasma P-selectin after long term dabigatran intake. According to previous experiment, P-selectin expression could facilitate the binding of platelet and leukocyte by the means of molecular cascades . Meanwhile, this phenomenon was not found under rivaroxaban treatment. Furthermore, we noticed that occurrence of DRT was associated with higher expressions of P-selectin mainly due to enhancement of platelet reactivity. Another adhesive protein on platelet surface, named CD40L, also played an important role in the inaction of platelet and leukocytes . No significant change was observed under either dabigatran and rivaroxaban anticoagulation.
Compared with dabigatran, the incident DRT was more uncommon at 90 days with rivaroxaban indicating that early rivaroxaban anticoagulation after implantation is largely protective. Meanwhile, the marked increase of DRT incidence at 3 months for post-implantation anticoagulation after LAAC operation with dabigatran suggested that dabigatran could enhance platelet reactivity in some LAAC operation patients. In our population, the follow-up TEE imaging displayed a higher ratio of DRT under anticoagulation with dabigatran, the adjusted post-anticoagulation therapy for LAAC was further needed.