Interrelationships between structure and function during the hemostatic response to injury

Significance Extensive studies have detailed the molecular regulation of individual components of the hemostatic system. Important questions remain, however, regarding how elements of the coagulation cascade, platelets, and the vessel wall are integrated at the systems level to achieve hemostasis in vivo. Here, in a series of high-resolution imaging studies, we explore in detail how a hemostatic plug composed of platelets and fibrin forms in the setting of penetrating vascular injuries. The results reveal a surprisingly heterogeneous hemostatic plug architecture, including gradients of platelet activation and spatial sequestration of thrombin activity outside the vessel lumen. They also show how a widely prescribed class of antiplatelet agents alters hemostatic plug architecture, resulting in adverse bleeding in certain physiologic contexts.