The function of tissue factor (Tf)-initiated coagulation is hemorrhage control through the formation and maintenance of an impermeable platelet-fibrin barrier. The catalytic processes involved in the clot maintenance function are not well defined, although the rebleeding problems characteristic of individuals with hemophilias A and B suggest a link between specific defects in the Tf-initiated process and defects in the maintenance function. We have previously demonstrated, using a methodology of "flow replacement" (or resupply) of ongoing Tf-initiated reactions with fresh reactants, that procoagulant complexes are produced during Tf-initiated coagulation which are capable of reinitiating coagulation without input from extrinsic factor Xase activity (Orfeo et al. J. Biol. Chem. 2005, 280: 42887). Here we use Tf-initiated reactions in normal and hemophilia blood or in their corresponding proteome mixtures as sources of procoagulant end products and then vary the resupplying material to determine the identity of the catalysts that drive the new cycle of thrombin formation. The central findings are: 1) the prothrombinase complex accumulated during the episode of Tf-initiated coagulation is the primary catalyst responsible for the observed pattern of prothrombin activation after resupply; 2) impairments in intrinsic factor Xase function, i.e. hemophilias A and B, result in an impaired capacity to mount a resupply response; and 3) in normal hemostasis, the intrinsic factor Xase function contributes to the durability of the resupply response.