Model of thrombus development. The top row shows the initial accumulation of platelets at a site of injury in a vessel. Subsequent rows show early fibrin clot development on the left (at ∼20 seconds), later events (at ∼150 seconds) in the middle, and degree of embolization on the right in that vessel. From top to bottom, the rows are for WT, untreated and treated FVIII^null, and pFVIII/FVIII^null mice as indicated. WT mice rapidly develop a fibrin scaffold that leads to vigorous platelet plug growth and little embolization. Untreated FVIII^null mice barely develop a fibrin clot and any accumulated platelet plug is unstable and rapidly breaks off. Treated FVIII^null mice develop a spatially and temporally correct clot, but of a limited size so that platelet plug development remains limited, but embolization approaches that seen in WT mice. The pFVIII/FVIII^null mice develop a rapid fibrin clot at the base, but it may be spatially more upstream than normal. Furthermore the core and top of the clot remain deficient in available FVIII, and the developing platelet plug is not well scaffolded. Frequent and relative large emboli then occur.