Factor VIIa-AT complex plasma levels and arterial thrombosis

摘要

The primary mechanism of the extrinsic coagulation pathway in vivo is tissue factor (TF) binding to activated factor VII (FVIIa) [1 ]. After initial activation, 2 mechanisms have been described to inhibit and control this pathway. The best understood mechanism for TF pathway inhibition is by the binding of TF pathway inhibitor (TFPI) to factor Xa, which then inhibits the TF-FVIIa complex [2]. Since the beginning of the eighties the inhibition of FVIIa by antithrombin (AT) has also been reported [3,4]. FVIIa is only susceptible to inhibition by AT when it is bound to TF and, different to the TFPI complex, the resulting FVIIa-AT complexes are released from TF into the circulation. The circulating levels of FVIIa-AT can be measured and reflect the degree of exposure of TF to blood. Heparin has shown to be absolutely required for this second-order kinetics inhibition. The biological and clinical significance of the AT-heparin inhibition of TF-FVIIa is unknown.