The saliva of hemovores, such as ticks, contains many anticoagulant molecules, which prevent the host from clotting so that the hemovore may feed. De Paula et al demonstrated that 1 tick anticoagulant, Ixolaris, works by binding the TF/FVIIa/FXa complex, similar to human TFPI. However, unlike TFPI, Ixolaris binds an exosite on FXa that induces a conformational change in its active site and loss of proteolytic function, a newly uncovered mechanism for regulating FXa function and limiting coagulation.