TISSUE FACTOR-INDUCED COAGULATION TRIGGERS PLATELET THROMBUS FORMATION AS EFFICIENTLY AS FIBRILLAR COLLAGEN AT ARTERIAL BLOOD-FLOW CONDITIONS

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 1:2x10(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 2600 s(-1)), less fibrin was deposited, but the platelet thrombus formation on the fibrin mesh increased dramatically. Platelet thrombus formation was elicited on top of the fibrin mesh; platelets adhered exclusively to the fibrin strands formed on the Thromborel S surface. However, while much less fibrin was deposited on the collagen (P<.001), the platelet-collagen adhesion was substantially higher than the platelet-fibrin adhesion on the Thromborel S surface (P<.001). Despite these differences, the platelet thrombus formation promoted by TF was comparable to that triggered by the collagen fibrils at intermediate and high arterial shear conditions.