title: Sepsis and disseminated intravascular coagulation.
abstract: Sepsis almost invariably leads to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). There is compelling evidence from clinical and experimental studies that DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. In addition, the massive and ongoing activation of coagulation, may deplete platelets and coagulation factors, which may in turn cause bleeding. Recent insights into important pathogenetic mechanisms that may lead to DIC have resulted in novel preventive and therapeutic approaches to patients with sepsis and a derangement of coagulation. Thrombin generation proceeds via the (extrinsic) tissue factor/factor VIIa route and simultaneously occurring depression of inhibitory mechanisms, such as antithrombin III and the protein C system. Also, impaired fibrin degradation, due to high circulating levels of PAI-1, contributes to enhanced intravascular fibrin deposition. Supportive strategies aimed at the inhibition of coagulation activation may be justified on theoretical grounds and have been found to be beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways, by means of the administration of antithrombin concentrate or recombinant human activated protein C.
authors.affiliation: Department of Internal Medicine/Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.m.levi@amc.uva.nl
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Evert
authors.initials: E
authors.lastname: de Jonge
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D006801:Humans; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000188:drug therapy
chemical_list: D000925:Anticoagulants