Thrombin Receptor Agonist Peptide–Induced Platelet Aggregation Is Reduced in Patients Receiving Dabigatran

Abstract

The availability of direct oral anticoagulants has caused a paradigm shift in thrombosis management. The direct thrombin inhibitor dabigatran seems to obstruct tenase complex by inhibiting thrombin generated in the initial phase and feed back to the amplification phase of cell-based coagulation reactions. However, it is still not fully understood if and how dabigatran impact platelet function. This observational study aimed to assess in vitro platelet function in patients with atrial fibrillation receiving dabigatran. Platelet aggregability was tested with platelet-rich plasma using platelet aggregometry (PACKS-4 aggregometer). Blood samples were stimulated with thrombin receptor agonist peptide (TRAP; 32 mmol/L). Results: A total of 28 patients with nonvalvular atrial fibrillation were enrolled. The mean age was 71.57 (9.75) years (range: 50-87 years), 16 patients were women, and the mean CHA 2 DS 2 VASc score was 3.93 (1.41). All patients began treatment with dabigatran as initial anticoagulant treatment. The minimum term use of dabigatran was 18 days. Dabigatran doses were 110 mg (57.14%) or 150 mg (42.86%) twice daily. The TRAPinduced platelet aggregation was significantly lower 2 hours after taking dabigatran compared to baseline value (79.39 [13.38] vs 90.14 [10.5]). Conclusion: The TRAP-induced platelet aggregation was reduced in cardiovascular patients 2 hours after receiving dabigatran. Our findings could have some important clinical implications because platelet aggregation and coagulation cascade are affected at the same time.

Impact of Edoxaban on Thrombin-Dependent Platelet Aggregation

“…Similar results were observed by TRAP-induced platelet aggregation in patients on dabigatran, rivaroxaban or apixaban treatment. 17,18 The study Vinholt et al and the herby presented study confirmed the hypothesis that DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) have an effect on platelet aggregation. In addition, Vinholt et al reported that the receptor expression of GPIIb/IIIa, CD63, and P-selectin were reduced after dabigatran treatment.…”

Antithrombotic therapy for atrial fibrillation and comorbidities — how to choose the optimal solution?

“…При ФП и стабильном течении ИБС для профилактики инсульта, СЭ и артериальных тромбозов достаточно монотерапии ОАК, т.к. эти препараты, снижая уровень тромбина в крови, оказывают и антиагрегантное действие, действуя через протеиназа-активируемые рецепторы 1, 4 типа, что снижает адгезию и агрегацию тромбоцитов [12]. При впервые возникшей ФП, в т.ч.…”

Impact of Dabigatran Treatment on Rotation Thromboelastometry

“… 8 As we have already mentioned, dabigatran inhibits thrombin, which has a key role in hemostasis with effects not only on plasma coagulation, but also on platelets. 9 , 10 Therefore, it is important to investigate the hemostatic effect of dabigatran on a whole blood sample. ROTEM is a method that allows this.…”