15 Differential Effects of NOAC and VKA onin VitroTest of Global Thrombotic Status

Abstract

Introduction The outcome of a thrombotic trigger, namely whether lasting vessel occlusion occurs or not, is determined the balance between prothrombotic properties of blood and endogenous thrombolysis. Atrial fibrillation (AF) is a major cause of stroke. Patients affected by AF are known to have enhanced thrombotic tendency. In our study we assessed the effect of novel oral anticoagulants (NOAC) and vitamin K antagonists (VKA) on global thrombotic status. Methods Patients with AF were tested to assess global thrombotic status before and during treatment with NOAC (dabigatran n = 12, rivaroxaban n = 9) and VKA (n = 13). Thrombotic status was assessed using the point-of-care Global Thrombosis Test (GTT). This technique utilises non-anticoagulated blood and assesses the time required for thrombus formation, occlusion (OT) and the time required for endogenous thrombolysis to occur, lysis time (LT). Results Compared to baseline, NOAC therapy resulted in a significant prolongation of OT [median 483s (25 th –75 th %ile: 395–556) vs. 714s (553–842), P Compared to baseline, VKA also prolonged OT [437s (313–550) vs. 639s (575–644), P = 0.007], with no significant effect on LT [1490s (1386–3368) vs. 1778s (1493–2365), P = 0.724]. The average INR was 2.5 ± 0.6 when the second sample was taken. The baseline thrombotic status for the NOAC and VKA group was similar [OT 483s vs. 437s P = 0.386; LT 1519s vs. 1490s, P = 0.326]. The was no significant difference in efficacy in between rivaroxaban and dabigatran and both agents prolonged OT (43 vs. 52%, P = 0.651) and reduced LT (22 vs. 56%, P = 0.917). The CHA 2 DS 2 VASC score was similar in the NOAC and VKA groups (2.8 ± 1.6 vs. 3.1 ± 2, P = 0.636). Conclusions The mechanism of action is different for NOAC and VKA. Both of them reduce platelet reactivity, evidenced by the prolongation of OT. NOAC, but not VKA, improve endogenous thrombolysis. This novel mechanism of action of NOAC may underpin the superiority of some NOAC in stroke reduction over VKA, but may also contribute to enhanced bleeding profiles.