title: Novel approaches to the management of disseminated intravascular coagulation.
abstract: OBJECTIVE
  Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. We addressed the issue of whether there is evidence that this fibrin deposition contributes to multiple organ failure. We also explored the current knowledge on the pathogenesis of DIC and reviewed current and future treatment for DIC.
  
  
  METHODS
  We searched and reviewed published articles on experimental studies of DIC models in animals and clinical studies in patients with DIC.
  
  
  RESULTS
  There is ample experimental and clinical evidence that DIC contributes to morbidity and mortality. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Although the trigger for the activation of the coagulation system may vary depending on the underlying condition, it is usually mediated by several cytokines. 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-protein S system. Also, impaired fibrin degradation, because of high circulating levels of plasminogen activator inhibitor, type 1, contributes to enhanced intravascular fibrin deposition.
  
  
  CONCLUSIONS
  Although the cornerstone of DIC management is the specific and vigorous treatment of the underlying disorder, strategies aimed at inhibiting coagulation activation may theoretically be justified. Such strategies have been found to be beneficial in experimental and initial clinical studies. These strategies, which follow from our current understanding of the pathophysiology of DIC, involve inhibition of tissue factor-mediated activation of coagulation or restoration of physiologic anticoagulant pathways by means of the administration of antithrombin concentrate or (activated) protein C concentrate. Although no complete evidence from controlled clinical trials is available for most of the proposed therapeutic interventions, these novel strategies are being studied.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: E
authors.initials: E
authors.lastname: de Jonge
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D011486:Protein C / Q000627:therapeutic use
chemical_list: D000991:Antithrombins; D011486:Protein C