Dabigatran inhibits thrombin generation differently than anti-Xa direct oral anticoagulants and uniquely displays profibrinolytic activity, with a significant correlation between changes in drug level and clot lysis time.
Observational (n=137)
No
Does dabigatran alter thrombin generation and improve profibrinolytic activity differently than anti-Xa DOACs in patients with atrial fibrillation and venous thromboembolism?
Dabigatran uniquely displays profibrinolytic activity and inhibits thrombin generation differently than anti-Xa DOACs, which may have implications for clot resolution in treated patients.
Effect estimate: rho=0.53
p-value: p=0.003
BACKGROUND: Recent reports suggest that direct oral anticoagulants (DOAC) may induce different anticoagulant and profibrinolytic responses. We performed a head-to-head comparison of the changes in thrombin generation (TG) parameters and tissue plasminogen activator (t-PA)-induced clot lysis produced by different DOAC. MATERIAL AND METHODS: We tested 137 plasma samples from patients with non-valvular atrial fibrillation (n=72) and venous thromboembolism (n=65) under treatment with apixaban (n=38), edoxaban (n=29), rivaroxaban (n=39), or dabigatran (n=31). TG was evaluated by a fluorometric assay and fibrinolysis by measuring the lysis time of clots exposed to 40 ng/mL t-PA. RESULTS: Trough-to-peak changes of TG parameters, along with correlation analysis, showed that all DOAC prolonged the lag-time in a concentration-dependent fashion. As for the other parameters, anti-factor Xa drugs markedly reduced the thrombin peak and velocity index but had little (rivaroxaban) or no effect on endogenous thrombin potential (ETP); dabigatran, instead, reduced ETP, weakly decreased thrombin peak and did not influence the velocity index, as also inferred from the changes in TG values after neutralisation of dabigatran with idarucizumab. Concerning the profibrinolytic effect of DOAC, intergroup comparison showed that the clot lysis time of dabigatran samples was significantly shorter than that of the apixaban and rivaroxaban samples, at both C-Trough and C-Peak. Moreover, a significant correlation between trough-to-peak changes in drug level and clot lysis time was only observed in the dabigatran group (rho=0.53). Finally, after DOAC removal by DOAC-stop, only dabigatran samples showed a significant increase in lysis time. DISCUSSION: Our data show that dabigatran inhibits TG in a different way than anti-Xa DOAC; moreover, under our conditions, only dabigatran displayed profibrinolytic activity, most likely because of its distinctive effect on the TG curve.
Dirienzo et al. (2022) conducted an observational in Non-valvular atrial fibrillation and venous thromboembolism (n=137). Direct oral anticoagulants vs. Between-DOAC comparison was evaluated on Thrombin generation parameters and tissue plasminogen activator-induced clot lysis time (rho=0.53, p=0.003). Dabigatran inhibits thrombin generation differently than anti-Xa direct oral anticoagulants and uniquely displays profibrinolytic activity, with a significant correlation between changes in drug level and clot lysis time.