Impact of dabigatran on platelet function and fibrinolysis

Abstract

Background: We sought to evaluate the potential enhanced fibrinolytic and antiplatelet activity of dabigatran etexilate (DE) due to decreased thrombin levels in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation (NVAF).

Methods: Consecutive patients with cerebrovascular diseases and NVAF that were treated with DE in a tertiary university hospital. Fibrinolysis and platelet function were assessed by thromboelastometry (ROTEM) and platelet function analyzer (PFA)-100, respectively, before and after treatment with DE. Conventional coagulation tests, endogenous thrombin potential (ETP) and hemoclot thrombin inhibitors (HTI), were also performed in order to detect any possible correlation between dabigatran plasma levels, its anticoagulant activity and the intensity of platelet dysfunction or fibrinolysis.

Results: A total of nineteen patients fulfilled our inclusion criteria (mean age 62.3±7.2years; 47% males; median CHADS2-score: 3; interquartile range: 2-4). DE treatment was associated with a significant reduction of the lysis index (LI60) at 60min (p=0.036), and prolongation of the PFA-100 CEPI closure time (p=0.024). After dabigatran treatment, abnormal PFA-100 results were obtained in two patients (11%, 95% CI: 2%-33%). DE levels (determined by HTI) were strongly inversely correlated (rho=-0.85; p<0.001) with the area under the curve (AUC) values in ETP assay. Νo association was found between HTI and PFA-100 CEPI CT (p=0.64), or LI60 measurements (p=0.60).

Conclusions: Our findings indicate that DE might affect platelet function and fibrinolysis and highlight the potential role of ETP as an alternative option in DE monitoring. The intensity and clinical relevance of DE antiplatelet and fibrinolytic effects require further investigation.

Keywords: Atrial fibrillation; Dabigatran; Direct thrombin inhibitor; Fibrinolysis; Ischemic stroke; Platelet function.