title: Tissue factor-induced coagulation triggers platelet thrombus formation as efficiently as fibrillar collagen at arterial blood flow conditions.
abstract: The relative importance of vessel wall tissue factor (TF) in initiating thrombogenesis is not well defined. In contrast, vessel wall collagens have been well documented as potent inducers of thrombus formation. We compared the potency of a human TF/phospholipid surface with that of a surface consisting of human type III collagen fibrils in triggering thrombus formation in native human blood at venous and arterial blood flow conditions. A commercial preparation, Thromborel S, was used as a source of human TF. Biochemical characterization of this preparation revealed small amounts of FVII, FIX, and FX proteins. Coagulant activity of these proteins was associated with the FVII protein only, although it was a very low activity. Studies with anti-TF antibodies in a one-stage clotting assay showed that the procoagulant activity of Thromborel was mainly a result of TF. The molar ratio of TF to phospholipid was 1:2 x 10(7). Thrombus formation in flowing nonanticoagulated human blood drawn directly from an antecubital vein was triggered by either Thromborel S or collagen fibrils coated on Thermanox coverslips in a parallel-plate perfusion chamber device. A 1:50 Thromborel S dilution gave maximal fibrin deposition (90% surface coverage) at a wall shear rate of 100 s-1. However, pretreatment of the TF surface with a monoclonal anti-TF antibody reduced this fibrin deposition by 93% (P < .001). Thus, TF was essential for the procoagulant activity of the Thromborel S surface in this flow system also. At higher wall shear rates (650 and 2600s-1), less fibrin was deposited, but the platelet thrombus formation on the fibrin mesh increased dramatically.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Nycomed Bioreg AS, Oslo, Norway.
authors.forename: U
authors.initials: U
authors.lastname: Orvim
authors.forename: H E
authors.initials: HE
authors.lastname: Roald
authors.forename: R W
authors.initials: RW
authors.lastname: Stephens
authors.forename: N
authors.initials: N
authors.lastname: Roos
authors.forename: K S
authors.initials: KS
authors.lastname: Sakariassen
mesh_terms: D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000032:analysis / Q000502:physiology; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000648:ultrastructure; D003094:Collagen / Q000502:physiology*; D005337:Fibrin / Q000648:ultrastructure; D006801:Humans; D010743:Phospholipids / Q000097:blood; D013925:Thromboplastin / Q000032:analysis / Q000502:physiology*; D013927:Thrombosis / Q000097:blood* / Q000503:physiopathology
chemical_list: D001779:Blood Coagulation Factors; D010743:Phospholipids; D005337:Fibrin; D003094:Collagen; D013925:Thromboplastin