Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

TG was quantified by time parameters: lag time (LT) and time to peak (TTP), and by amount of TG: peak of TG (PTG) and area under thrombin formation curve after 35 minutes (AUC→35min) in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT) technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA), ADP, and collagen (Col). In addition, the effects of recombinant activated FVII (rFVIIa) alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p < 0.05) and PTG and AUC→35min were significantly increased (p < 0.05) in platelet rich plasma activated with AA, ADP, Col, and rFVIIa compared to non-activated platelet rich plasma from normal subjects (p = 0.01). Furthermore platelet rich plasma activated by the combined effects of rFVIIa plus AA, ADP or Col had significantly reduced LT and TTP and increased AUC→35min (but not PTG) when compared to platelet rich plasma activated with agonists in the absence of rFVIIa.Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.Tissue factor (TF) exposed after endothelial injury binds FVIIa to initiate thrombin generation (TG). In addition Factor VIIa on surface of platelets may cause TG in the absence of TF involvement [1,2]. In this process the transbilayer movement of phosphatidylserine through the flip-flop mechanism [3,4] likely provides the necessary procoagulant phospholipid surface. Thus platelets play a role in thrombin formation and thrombin is a potent platelet activator. Platelets that adhere to the exposed subendothelium [5] after endothelial inju