title: Factor VIII contributes to platelet-fibrin thrombus formation via thrombin generation under low shear conditions.
abstract: BACKGROUND
  Thrombus growth under low blood flow velocity plays an important role in the development of deep venous thrombosis (DVT). Increased plasma levels and activities of coagulation factor VIII (FVIII) comprise risk factors for DVT and pulmonary thromboembolism.
  
  
  OBJECTIVE
  To localize FVIII in human venous thrombi of DVT and to determine whether FVIII contributes to thrombus formation under low shear conditions.
  
  
  METHODS
  The localization of FVIII in venous thrombi obtained from patients with DVT was examined by immunohistochemistry. The role of FVIII in thrombus formation was investigated using a flow chamber system. Venous blood from healthy volunteers were incubated with an anti-FVIII monoclonal antibody (VIII-3776) or non-immunized mouse IgG(1). Blood samples were perfused on immobilized type III collagen at wall shear rates of 70/s and 400/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1+2 (PF1+2) generation was measured before and after perfusion.
  
  
  RESULTS
  Venous thrombi of DVT comprised a mixture of platelets, fibrin and erythrocytes. Factor VIII appeared to be colocalized with glycoprotein IIb/IIIa, fibrin and von Willebrand factor in the thrombi. VIII-3776 specifically recognized the light chain of FVIII and prolonged the activated partial thromboplastin time (aPTT), but not prothrombin time (PT). The antibody significantly reduced platelets and fibrin covering, as well as PF1+2 generation at wall shear rates of 70/s and 400/s.
  
  
  CONCLUSIONS
  These results suggest that FVIII contributes to platelet aggregation and fibrin formation via thrombin generation under low shear conditions.
authors: Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors: Chihiro
authors: C
authors: Sugita
authors: Atsushi
authors: A
authors: Yamashita
authors: Sayaka
authors: S
authors: Moriguchi-Goto
authors: Eiji
authors: E
authors: Furukoji
authors: Misaki
authors: M
authors: Takahashi
authors: Aya
authors: A
authors: Harada
authors: Tetsuhiro
authors: T
authors: Soeda
authors: Takehisa
authors: T
authors: Kitazawa
authors: Kunihiro
authors: K
authors: Hattori
authors: Shozo
authors: S
authors: Tamura
authors: Yujiro
authors: Y
authors: Asada
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008875:Middle Aged; D010974:Platelet Aggregation / Q000502:physiology; D033081:Shear Strength; D013917:Thrombin / Q000378:metabolism; D020246:Venous Thrombosis / Q000097:blood* / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D005169:Factor VIII; D005337:Fibrin; D003094:Collagen; D013917:Thrombin