title: The coagulopathy of acute sepsis.
abstract: OBJECTIVE
  Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the coagulation system becomes diffusely activated, with consumption of multiple clotting factors resulting in disseminated intravascular coagulation (DIC). When present, DIC portends a higher mortality rate. Understanding the mechanisms that tie inflammation and diffuse thrombosis will allow therapeutic interventions to be developed. The coagulopathy of acute sepsis is a dynamic process that is time and disease burden specific. Whole-blood testing of coagulation may provide more clinically useful information than the classical tests. Natural anticoagulants that regulate thrombosis are downregulated in sepsis. Patients may benefit from the modulation of the coagulation system when systemic inflammation and hypercoagulopathy exist. Proper timing of anticoagulant therapy may ultimately lead to decreased incidence of multisystem organ dysfunction.
  
  
  RESULTS
  The pathogenesis of coagulopathy in sepsis is driven by an upregulation of procoagulant mechanisms and simultaneous downregulation of natural anticoagulants. Inflammation caused by the invading organism is a natural host defense that cannot be eliminated during treatment. Successful strategies to prevent multisystem organ dysfunction center on stratifying patients at high risk for DIC and restoring the balance of inflammation and coagulation.
  
  
  CONCLUSIONS
  The prevention of DIC in septic patients is a key therapeutic target in preventing death from multisystem organ failure. Stratifying patients for therapy using thromboelastometry, specific markers for DIC, and composite scoring systems is an area of growing research.
authors.affiliation: aAnesthesia Services Division, Trauma Section, UAB Department of Anesthesiology bCritical Care Division, Department of Anesthesiology cCenter for Lung Injury and Repair, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Simmons
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Pittet
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000628:therapy*; D001780:Blood Coagulation Tests; D004211:Disseminated Intravascular Coagulation / Q000628:therapy; D006801:Humans; D009102:Multiple Organ Failure / Q000628:therapy; D018805:Sepsis / Q000150:complications* / Q000628:therapy; D013927:Thrombosis / Q000209:etiology