Natural Coagulation Inhibitors and Inflammation.

mostasis and inflammation are closely related processes. It is recognized that the activation of hemostasis fosters, to a certain extent, inflammation and that inflammation, in turn, activates the hemostasis system. These interrelationships are best illustrated in sepsis, were microorganisms or their release products, most notably cytokines, causing inflammation, activate the hemostasis system. This process starts early in the inflammatory response. Already at the time of systemic inflammatory response syndrome (SIRS) there is evidence of an accelerated activation of the hemostasis system[1]. Levels of molecular markers of in vivo hemostasis activation begin to rise and increase further as inflammation progress. This process may ultimately lead to disseminated intravascular coagulation (DIC), also known as consumptive coagulopathy or thrombohemorrhagic syndrome[2,3]. Initially DIC is clinically unrecognized because it is compensated i.e. the increased consumption of coagulation componets is compensated for by an increased production. Routinely performed laboratory tests may still be normal, although elevated fibrinogen and D-dimer levels as well as decreased platelet counts may serve as early indicators[4]. If the inflammatory process is not aggressively controlled, DIC may decompensate. This is clinically recognized by a diffuse and profuse bleeding tendency, and laboratory data reveal consumption of many coagulation factors and platelets, leading ultimately to a complete breakdown of the hemostasis system, i.e. the bleeding tendency[2]. While hemorrhages are readily recognized, the thrombotic component of DIC is difficult to assess until signs of the multiple organ dysfunction syndrome (MODS) become evident[5]. There is considerable data to suggest that MODS is closely related to diffuse fibrin depositions in the microvasculature[6]. This would imply that the fibrinolytic system is malfunctioning. Early in sepsis the fibrinolytic system is also activated, but as the process progresses, the fibrinolytic system becomes inhibited by the release of plasminogen activator inhibitor 1 (PAI-1), the main regulator of fibrinolytic activation[7,8].