Hypothetical model for the role of GPIbα in the mechanism of action of rFVIIa. (A) On the resting platelet, the interaction between rFVIIa and the GPIb-IX-V complex (depicted as “Ib”) does not occur, as the resting platelet does not express negatively charged phospholipids, and presumably because the GPIb-IX-V complex is not in a rFVIIa-binding membrane environment. (B) After activation of the platelet, rFVIIa is able to interact with the GPIb-IX-V complex. This interaction is critically dependent on the negatively charged surface but may also involve translocation of the GPIb-IX-V complex to an anionic or lipid raft region of the platelet surface. Alternatively, the interaction might require a conformational change with the GPIb-IX-V complex. The interaction of rFVIIa with GPIb results in acceleration of Xa generation.