Summary
Blood coagulation has been thought to be composed of both intrinsic and extrinsic
pathways. Recent evidence strongly supports the critical role of the extrinsic pathway
in the initiation of blood coagulation. This investigation established an assay that
examines the role of FXI in the thromboplastin-initiated (extrinsic) coagulation based
on this new concept. Plasma clotting times were measured at different concentrations
of thromboplastin with activated FXII inhibited (FXIIa-inhibited Diluted Thromboplastin
Time, FXIIaiDTT). Only at low concentrations of thromboplastin was FXIIaiDTT of FXI-deficient
plasma significantly prolonged than that of normal plasma. Depletion of FXI from normal
plasma prolonged its FXIIaiDTT and replenishment of FXI shortened it. FXIIaiDTTs of
both FVIII-deficient and FIX-deficient plasma were remarkably prolonged, and addition
of normal plasma dose-dependently shortened it. Furthermore, earlier α-thrombin inhibition
was directly correlated with decreasing FXa generation. The amount of FXa production
was: platelet-rich plasma > platelet-poor plasma > FXI-deficient plasma. Therefore,
our findings from the FXIIaiDTT assays not only support the critical role of extrinsic
pathway in blood coagulation initiation, but also demonstrate the importance of FXI
as an amplifier of thrombin generation in thromboplastin-initiated coagulation.
Key words
Blood coagulation - thromboplastin - factor VIII - factor IX - factor XI
