Potential consequences of coagulation activation during sepsis. Recognition of invading pathogens by innate immunity triggers mechanisms that contribute to pathogen clearance such as endothelial activation and recruitment of immune cells to infection sites. Coagulation activation is part of this stereotyped response. During sepsis, increased tissue factor expression, down-regulation of natural anticoagulant pathways, and hypofibrinolysis result in increased thrombin generation and clot formation. The beneficial consequences of coagulation activation for pathogen clearance are depicted in panel A and include the release of antimicrobial peptides from the proteolysis of several proteins of the coagulation cascade, and limitation of pathogen spread by fibrin-mediated hemostatic containment. However, deregulated coagulation activation could also contribute to microvascular thrombosis and hypoxia, thereby contributing to tissue damage in sepsis. The precise identification of the moment when coagulation activation turns from a beneficial to a detrimental process would allow more rational therapeutic approaches for sepsis, preserving the ancient link between hemostasis and innate immune response. PAI-1: plasminogen activator inhibitor-1.