This second figure is of thrombin generation on platelet surfaces. In normal hemostasis, FIXa combines with FVIIIa on the activated platelet surface to activate FX. The FXa, in turn, combines with FVa to produce thrombin. In severe hemophilia, there is no platelet surface mechanism to activate FX. When high-dose FVIIa is used as a bypassing agent, it binds to the activated platelet surface and activates small amounts of FX. The resulting FXa is able to partially restore platelet surface thrombin generation. The binding and activity of FVIIa is mediated by negatively charged phospholipid, the GPIb/IX/V complex, and possibly other binding proteins that are unrecognized as of yet. Professional illustration by Debra Tyler Dartez.