A model for hemostatic plug formation dictated by the interaction of local conditions with the platelet signaling network. The data presented show that during initial formation and up to 1 hour post-injury, a hemostatic plug is comprised of distinct regions defined by the degree of platelet activation and packing density, as depicted in panel A. The characteristics of each region are indicated in A. We propose that this architecture is a result of a gradient of soluble agonists emanating from the site of injury, as shown in (B). Thrombin generation at the site of injury drives platelet activation in the core region (blue to purple/pink in the figure), but its propagation away from the vessel wall is limited. A gradient of ADP and potentially TxA2 emanating from activated platelets (purple to red in the figure) extends farther and results in the recruitment of additional platelets forming the shell region. Additional platelet signaling, such as contact-dependent signaling pathways, reinforces the architecture via local positive feedback.
