Baboon Model of E. coli Sepsis: Role of Phospholipid Microparticles in DIC

This chapter describes our experience with primate models of E. coli sepsis with emphasis on the responses of the hemostatic system, the mechanism of these responses, and the role of phospholipid microparticles in mediating disseminated intravascular coagulation (DIC). Understanding the principles of how the hemostatic system responds to inflammatory stress depends on viewing this system as a collection of mediator and regulator factors all of which are integrated with each other to control either the patency or the integrity of the cardiovascular system.The first section of this chapter describes these four functional domains: coagulant versus anticoagulant and fibrinolytic versus antifibrinolytic domains. The functions of all four of which are regulated by thrombin through its interaction with either the endothelium or platelets. This is followed by a review of modulators, which influence the balance between the four functional domains. Emphasis is placed on how modulators such as estrogen, interleukin-6, etc., act to influence the balance between procoagulant mediators (i.e., factor Xa plus phospholipid microparticles) and anticoagulant and fibrinolytic regulators (protein C, plasminogen activator).The second section describes how this system responds to inflammatory stress in a series of reconstitution and intervention studies. Attention is given to the role of phospholipid microparticles, and to defining those clinical pathophysiologic settings in which the hemostatic system is a link in a lethal chain of events versus those in which it acts in parallel (epiphenomenon).