Abstract Number: PB2062
Meeting: ISTH 2020 Congress
Background: Recent reports suggest that DOACs may induce different anticoagulant and profibrinolytic responses.
Aims: Head-to-head comparison of the changes in thrombin generation parameters and t-PA-induced clot lysis induced by different DOACs.
Methods: We studied 137 patients (72 AF, 65 VTE) under treatment with apixaban (n=38), edoxaban (n=29), rivaroxaban (n=39), or dabigatran (n=31). Plasma samples were taken at C-trough and C-peak. Thrombin generation was evaluated by calibrated automated thrombogram (CAT). For dabigatran samples, the internal calibrator was supplemented with idarucizumab to neutralize dabigatran. Lysis time of clots exposed to 40 ng/ml t-PA was assessed by turbidimetry.
Results: C-peak drug levels were 2-fold (apixaban and dabigatran) to 6-8 fold higher than C-trough levels. C-peak samples displayed longer lagtime and lower peak thrombin than C-trough samples for all drugs, whereas C-peak ETP was reduced only in dabigatran and rivaroxaban samples. Moreover, ETP was lower and peak thrombin higher in dabigatran samples as compared to all “xabans”. Rank correlation showed that the levels of each xaban were strongly correlated with lagtime and peak thrombin (rho>0.7) whereas dabigatran levels were best correlated with lagtime and ETP (rho=>0.62). Clot lysis time was significantly shorter in C-peak than in C-trough in all groups but apixaban. Intergroup comparison showed that clot lysis time of dabigatran samples was significantly shorter than that of xabans, at both C-trough and C-peak. Moreover, a significant correlation between drug level and clot lysis changes was only observed in dabigatran group (rho=0.53). Finally, a strong correlation between clot lysis time and both peak thrombin and ETP was only seen in dabigatran group (rho ≥ 0.51).
Conclusions: Thrombin generation may represent a valid assay to assess the anticoagulant effect of DOACs, provided that the right CAT parameters are considered for each type of drug. The greater profibrinolytic activity of dabigatran may improve its antithrombotic efficacy.
To cite this abstract in AMA style:Dirienzo L, Vitulli A, Ammollo CT, Mancazzo F, Dellanoce C, Paoletti O, Testa S, Colucci M. Differential Effect of Direct Oral Anticoagulants (DOACs) on Thrombin Generation and Clot Lysis in Patients with Non Valvular Atrial Fibrillation (AF) and Venous Thromboembolism (VTE) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/differential-effect-of-direct-oral-anticoagulants-doacs-on-thrombin-generation-and-clot-lysis-in-patients-with-non-valvular-atrial-fibrillation-af-and-venous-thromboembolism-vte/. Accessed January 23, 2022.
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