Following injury or invasion by a pathogen, the body protects against the loss of blood and attempts to maintain hemostasis by activating the primary and secondary hemostatic pathways.* The culmination of these events is the formation of a fibrin-rich platelet plug at the site of vessel damage. Along with its role in hemostasis, fibrin also plays roles in the inflammatory and wound healing processes that are occurring simultaneously following an injury (see Chapter 2). Fibrin deposition is seen frequently in areas of inflammation, whether vessel injury is present or not. Local fibrin deposition is able to induce adhesion molecule expression and chemokine expression in the endothelium, leading to recruitment of leukocytes and fibroblasts to the site of injury. Fibroblasts play a key role in the wound healing processes, as they secrete matrix proteins, namely fibronectin and collagen. The foundation formed by this provisional matrix allows for reepithelialization of the injury, as local epithelial cells migrate to the wound and provide a protective covering. Finally, fibrin is able to directly interact with the integrin αMβ2 on the surface of leukocytes, leading to further recruitment of white blood cells to the site of injury.
The interplay between hemostasis and inflammation is a well-studied mechanism present in primitive organisms, such as the horseshoe crab, that have integrated coagulation and immune systems. Although more complex species have developed separate specialized hemostatic and inflammatory systems, the two have never become mutually exclusive. Inflammation triggers activation of coagulation and, conversely, coagulation triggers activation of inflammation. One of the earliest mediators of primary hemostasis, the platelet, secretes not only signaling molecules but also a barrage of inflammatory cytokines and chemokines from granules, leading to the recruitment of leukocytes to the site of injury.
In addition to being the most critical enzyme involved in the coagulation cascade, thrombin has many roles outside of hemostasis. It is able to activate several cell types to secrete proinflammatory mediators by binding to protease-activated receptors (PARs) on the surface of platelets, endothelial cells, fibroblasts, smooth muscle cells, and many other nonhemostatic cell types. The presence of inflammation can shift the endothelium from an anticoagulant surface, whose functions are detailed further in this text, to a procoagulant surface by inducing expression of coagulation molecules such as von Willebrand factor (vWF), tissue factor (TF), and plasminogen activator inhibitor-1 (PAI-1), and by reducing the expression of thrombomodulin (TM). These procoagulant endothelial cells may also release procoagulant microparticles containing both PTS, the phospholipid critical for thrombus formation, and TF on their surface, leading to increased amounts of circulating TF and increased fibrin formation.
In more simplified terms, hemostasis consists of three essential elements: vessels, platelets, and coagulation proteins. In normal hemostasis, all of these constituents influence each other to maintain the fluidity of blood, only leading to clot ...