Inhibition of factor XI reduces thrombus formation in rabbit jugular vein under endothelial denudation and/or blood stasis.
BACKGROUND
In addition to acquired and inherited risk factors, the growth of venous thrombus under static conditions and endothelial injury play important roles in the development of deep venous thrombosis (DVT), for which risk factors include increased plasma levels of coagulation factor XI (FXI). The aim of this study is to understand the role of FXI in venous thrombus formation under conditions of endothelial denudation and/or blood stasis.


METHODS
The contribution of FXI to venous thrombus formation was investigated in a rabbit model and a flow chamber system. Thrombi were induced in the rabbit jugular veins by (1) endothelial denudation, (2) vessel ligation (blood stasis) or (3) by combined endothelial denudation and vessel ligation. Blood samples were perfused on immobilized type III collagen at a wall shear rate of 70/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1+2 (F1+2) generation was also measured before and after perfusion.


RESULTS
All thrombi induced in rabbit jugular veins were composed of platelets, fibrin and erythrocytes. Anti-FXI antibody significantly reduced ex vivo plasma thrombin generation initiated by ellagic acid but not by tissue factor, and in vivo thrombus formation under endothelial denudation and/or vessel ligation. The antibody significantly reduced surface areas covered by platelets and fibrin, as well as F1+2 generation at a wall shear rate of 70/s in flow chambers.


CONCLUSIONS
These results suggest that FXI contributes to venous thrombus growth under conditions of endothelial denudation and/or blood stasis, and that thrombin generation by FXI interaction promotes further platelet aggregation and fibrin formation at low shear rates.
Takahashi
Misaki
M
Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Yamashita
Atsushi
A
Moriguchi-Goto
Sayaka
S
Sugita
Chihiro
C
Matsumoto
Tomoko
T
Matsuda
Shuntaro
S
Sato
Yuichiro
Y
Kitazawa
Takehisa
T
Hattori
Kunihiro
K
Shima
Midori
M
Asada
Yujiro
Y
D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology* / Q000601:surgery; D005172:Factor XI / Q000037:antagonists & inhibitors*; D007601:Jugular Veins / Q000503:physiopathology*; D011817:Rabbits; D020246:Venous Thrombosis / Q000503:physiopathology* / Q000517:prevention & control*
D005172:Factor XI