Activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor.

摘要: Activation of coagulation factor XI (FXI) may play a role in hemostasis. The primary substrate activated FXI (FXIa) is FIX, leading to FX activation (FXa) and thrombin generation. However, recent studies suggest the hemostatic not be restricted FIX. We explored whether could interact with inhibit activity tissue pathway inhibitor (TFPI). TFPI an essential reversible X also inhibits FVIIa-TF complex. found that FXIa neutralized both endothelium- platelet-derived by cleaving protein between Kunitz (K) 1 K2 domains (Lys86/Thr87) at active sites (Arg107/Gly108) K3 (Arg199/Ala200) domains. Addition plasma was able reverse ability prolong TF-initiated clotting times FXI- or FIX-deficient plasma, as well FXa-initiated FX-deficient plasma. Treatment cultured endothelial cells increased generation FXa promoted TF-dependent fibrin formation recalcified Together, these results attributed only FIX but promoting extrinsic through inactivation TFPI.