Direct thrombin inhibitors in atrial fibrillation reloaded.

摘要

Inhibition of plasrhatic coagulation is the key therapeutic principle for thromboprophylaxis and stroke prevention in atrial fibrillation. The coagulation cascade is initiated by contact of tissue factor (TF) with circulating factor (F) Vila, resulting in the formation of the TF-Vlla complex. The latter catalyses the conversion of FIX to IXa and FX to Xa. Together with FVa, phospholipids, and calcium, FXa forms the 'tenase' or 'prothrombinase' complex, which catalyses the conversion of prothrombin (Fll) to thrombin (Flla), eventually resulting in fibrin formation and generation of a thrombus.1 Thrombin furthermore activates FV, FVIII, and FXI by means of an auto-feedback loop, leading to the conversion of large amounts of FX to FXa and thereby to a sustained activation of coagulation (Figure 1).