title: Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock.
abstract: In patients with sepsis and septic shock, both coagulation and fibrinolysis are activated frequently leading to the syndrome of diffuse intravascular coagulation (DIC). The different mechanisms leading to abnormalities in coagulation and fibrinolysis are discussed in detail. The coagulation and fibrinolytic system appear to be influenced by the septic process largely independently, leading to a procoagulant imbalance between these systems. Coagulation is initiated by mediator-induced expression of tissue factor and is associated with consumption of the natural coagulation inhibitors antithrombin III, protein C, and protein S. As a result, high plasma levels of thrombin-antithrombin complex (TAT) can be found. The effects on fibrinolysis are dominated by (highly) increased levels of plasminogen activator inhibitor type 1 (PAI-1), leading to inadequate fibrinolysis. Although levels of plasminogen activator antigen are increased, its activity is almost completely inhibited by PAI-1. The resulting effects predispose to a procoagulant state, with widespread fibrin deposition, which may be an important mechanism contributing to multiple organ failure. A thorough understanding of the pathophysiological mechanisms underlying the DIC-syndrome is a prerequisite for a rational approach and future therapy for this severe complication of sepsis.
authors.affiliation: Medical Intensive Care Unit of the University Hospital VU Amsterdam, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Vervloet
authors.forename: L G
authors.initials: LG
authors.lastname: Thijs
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
mesh_terms: D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D005342:Fibrinolysis; D006801:Humans; D018805:Sepsis / Q000150:complications* / Q000503:physiopathology; D012772:Shock, Septic / Q000150:complications / Q000503:physiopathology