Factor VIIa activation of factor X. (A) Baseline mechanism: On a lipid surface, factor VII binds to tissue factor (TF) and is slowly activated, either by the 1% of plasma factor VII that is activated or by factor Xa generated by other VIIa/TF complexes. This VIIa/TF complex activates factor X to factor Xa before ultimately being shut off by tissue factor pathway inhibitor (TFPI; not shown). (B) Tissue factor–dependent (competition) mechanism: On a lipid surface, factor VIIa can compete with factor VII for binding to TF. The VIIa/TF complexes can immediately begin activating factor X without requiring a slow activation step. The VIIa/TF complexes can also activate any TF-bound factor VII, further speeding factor X activation. (C) Tissue factor–independent mechanism: In addition to binding to tissue factor, factor VIIa can bind lipid surfaces and convert factor X to factor Xa. This reaction is much slower than the reaction of TF-bound factor VIIa; however, the amount of surface-bound factor VIIa may exceed the amount of TF-bound by orders of magnitude. This reaction is also limited by the amount of available surface. Unlike factor VIIa in a TF complex, factor VIIa without TF is not inhibited by TFPI.