THE EFFECTS OF ACTIVATED FACTOR-VII IN A CELL-BASED MODEL FOR TISSUE FACTOR-INITIATED COAGULATION

The importance of activated factor VII (FVIIa) in coagulation initiate d by tissue factor (TF) was illustrated by competition of active site- inhibited FVIIa (FFR-FVIIa; FVIIa treated with D-Phe-Phe-Arg-chloromet hyl ketone) with FVIIa in various cell-based assays mimicking TF-initi ated coagulation. FFR-FVIIa inhibited the overall initiation process a s measured by platelet activation and large-scale thrombin generation on the activated platelet surface. When the individual steps in the in itiation process were separated, FFR-FVIIa affected only the reactions taking place on TF-bearing cells, demonstrating that FVIIa takes part only in the very first step in the initiation process. The dissociati on constant (K-d) for FVIIa binding to TF and the inhibition constant (K-i) for FFR-FVIIa competing with FVIIa in binding to TF, measured in a factor X activation assay, were both around 10 pmol/l, showing that FVIIa and FFR-FVIIa bound to TF in the extrinsic pathway tenase compl ex with the same affinity. Blood Coag Fibrinol 9 (suppl 1):S21-S25 (C) 1998 Lippincott-Raven Publishers