Hypothetical configuration of the FX-activating complex. A cartoon showing how the triangular array of the FVIII A1, A2, and A3 domains may be anchored to a phospholipid surface via the C1 and C2 domains (not to scale). The FIXa serine protease domain interacts with the loop in A2 (S558-Q565), whereas the FIXa EGF2 domain binds to the loop in A3 (E1811-K1818). The FIXa Gla domain is also anchored to the phospholipid surface via a calcium-dependent mechanism. This complex between FVIII and FIXa activates zymogen FX as a key step in the amplification of the initial trigger in coagulation.