Decrease of Aggregation By Platelet Impedance Aggregometry ( MULTIPLATE ) in Patients Treated with Dabigatran

Introduction: Dabigatran is a direct oral anticoagulant (DOAC) that has been proved effective and safe in preventing thromboembolic events experienced by patients with non-valvular atrial fibrillation (AF). This drug acts directly inhibiting thrombin and particularly affects the intrinsic and the final coagulation pathways. Thrombin is a platelet agonist therefore dabigatran could be involved in altering the aggregation. However, it is not well known whether they modify the platelet function. We conducted an initial study in our hospital to assess platelet aggregation in patients treated with dabigatran.

Methods: An observational study was conducted in 17 randomly selected patients who had started dabigatran in the last year in our center. The results were compared with 8 healthy platelet donors randomly selected from our database. Platelet aggregation was quantified in patients and controls using MEA (Multiplate, Roche Diagnostics, Switzerland). The indication and dosing of dabigatran was performed as clinically indicated. The main variables investigated were: aggregation time with four agonists: thrombin, ADP, collagen, ristocetin, APTT, INR addition, D Dimer, kidney and liver function and the usual demographic parameters. Statistical analysis were performed using SPSS 21.0 (SPSS Inc., Chicago, IL).

Results: All patients had AF as an indication for treatment with dabigatran. Dabigatran doses were 110 mg in 7 patients (41%) and 150 mg in 10 patients (58%). No patient was on any antiplatelet agent. Platelet aggregation induced by TRAP measured by MEA was not significantly different in patients compared to controls: 121 RI (94-127) vs. RI 122 (108-137) units (p = 0.711). Aggregation using collagen and ristocetin as agonists was significantly decreased compared to that of controls: RI 48 (32-63) vs. 83 RI (69-110) (p = 0.05) and 76 RI (71-32) vs. 120 RI (97-142) units (p <0.01). There were no differences in the aggregation depending on the dose of dabigatran. Conclusion: Despite the limitations of the study we observed a change in the aggregation of patients treated with dabigatran measured by MEA, compared with healthy controls. Contrary to what one might expect, it was not dependent on the thrombin pathway unless the ristocetin and collagen agonists. These findings must be confirmed in more powerful studies designed for this purpose because others studies, with the same characteristics than our work, have shown TRAP-induced platelet aggregation enhance in patients treated with dabigatran.¹

^{1TRAP-induced platelet aggregation is enhanced in cardiovascular patients receiving dabigatran.Christoph B. Olivier et al. Thrombosis Research Thromb Res. 2016 Feb;138:63-8}