A model of GPIb-IX activation via crosslinking by antibodies against the LBD. In this model, an anti-LBD antibody binds to 2 copies of GPIb-IX on opposing platelets, thereby crosslinking them. Under shear flow, this crosslinking allows the exertion of force on GPIb-IX, subsequent unfolding of the MSD, and signaling into the platelet, which leads to clearance. The ability to crosslink platelets under shear depends on a sufficiently high unbinding force between the antibody and its epitope in the LBD. Antibodies with low unbinding force to the LBD, such as AK2, cannot effectively crosslink platelets and thus cannot exert a shear force to unfold the MSD of GPIb-IX.