Effects of dabigatran in vitro on thrombin biomarkers by Calibrated Automated Thrombography in patients after ischemic stroke.

摘要

Randomized trials suggest superior and safe stroke prevention in patients with atrial fibrillation after anticoagulation with dabigatran (D) at a 150?mg BID as described in the RE-LY prospective randomized open-label trial when compared to warfarin. Thrombin generation (TG) is a cornerstone of coagulation cascade, and represents a critical biomarker of atherothrombosis. We, therefore, sought to define the effect of D in escalating concentrations on the time course of TG using the Calibrated Automated Thrombogram(?) (CAT) technology in patients after ischemic stroke. Serial plasma samples were obtained from 20 patients with ischemic stroke documented by neuroimaging, who were treated with aspirin for at least 30?days. The impact of 0.1, 0.23, 0.46, 0.69?mM D in platelet-poor plasma (PPP) on TG indices was assessed using fluorogenic substrate CAT device. The following integrated CAT parameters: TGmax, start time (t-start) peak time (t-peak), and mean time (t-mean) were calculated for each D dose and compared with those of the vehicle. Preincubation of PPP with D resulted in dose-dependent significant inhibition of most TG indices. The TGmax was gradually reduced from 447?±?21?nM at baseline and reach significance for 0.46?mM D (355?±?44?nM, P?=?0.03); and decreased further at 0.69?mM D to 302?±?27?nM (P?=?0.01). The t-peak has been achieved 2-3 times later than after vehicle already at 0.23?nM D. The t-start was delayed 3-4 fold starting from 0.23?mM concentration of D (P?