The role of factor XI in a dilute thromboplastin assay of extrinsic coagulation pathway.
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 alpha-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.
He
R
R
Department of Physiology, Hunan Medical University, Changsha, PR China. rhe25@hotmail.com
Xiong
S
S
He
X
X
Liu
F
F
Han
J
J
Li
J
J
He
S
S
D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D005169:Factor VIII / Q000494:pharmacology; D005172:Factor XI / Q000494:pharmacology / Q000502:physiology*; D015951:Factor Xa / Q000187:drug effects; D006490:Hemostatics; D006801:Humans; D010314:Partial Thromboplastin Time; D010940:Plant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013925:Thromboplastin
D006490:Hemostatics; D010940:Plant Proteins; C052160:trypsin inhibitor, Zea mays; D005169:Factor VIII; D005172:Factor XI; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa