Upon activation, platelets mediate responses central to inflammatory and immune activities. Pathogens, pathogen-derived agonists, and circulating systemic factors present in the septic milieu such as thrombin, adenosine diphosphate (ADP), and others activate circulating human platelets (indicated by blue cells). Platelet activation results in upregulation of surface integrins, such as integrin αIIbβ3, binding of plasma fibrinogen, the formation of platelet-platelet and platelet-leukocyte aggregates, display and release of p-selectin, CD40L and other mediators, secretion of antimicrobial factors, and signaling to other target cells. These responses can be both adaptive and maladaptive to the host during infectious syndromes (modified from Rondina et al.⁸ ).