title: Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis.
abstract: BACKGROUND
  Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant and fibrinolytic derangements of trauma-induced shock.
  
  
  METHODS
  This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1 + 2 (PF1 + 2), fibrinogen, factor VII, thrombomodulin, protein C, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), and D-dimers. Base deficit was used as a measure of tissue hypoperfusion.
  
  
  RESULTS
  Two hundred eight patients were studied. Systemic hypoperfusion was associated with anticoagulation and hyperfibrinolysis. Coagulation was activated and thrombin generation was related to injury severity, but acidosis did not affect Factor VII or PF1 + 2 levels. Hypoperfusion-induced increase in soluble thrombomodulin levels was associated with reduced fibrinogen utilization, reduction in protein C and an increase in TAFI. Hypoperfusion also resulted in hyperfibrinolysis, with raised tPA and D-Dimers, associated with the observed reduction in PAI-1 and not alterations in TAFI.
  
  
  CONCLUSIONS
  Acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis. There was no evidence of coagulation factor loss or dysfunction at this time point. Soluble thrombomodulin levels correlate with thrombomodulin activity. Thrombin binding to thrombomodulin contributes to hyperfibrinolysis via activated protein C consumption of PAI-1.
authors.affiliation: Department of Surgery, The Royal London Hospital, London, United Kingdom.
authors.forename: Karim
authors.initials: K
authors.lastname: Brohi
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Cohen
authors.forename: Michael T
authors.initials: MT
authors.lastname: Ganter
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Robert C
authors.initials: RC
authors.lastname: Mackersie
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Pittet
mesh_terms: D001779:Blood Coagulation Factors / Q000302:isolation & purification*; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology; D005342:Fibrinolysis; D006801:Humans; D015601:Injury Severity Score; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D014193:Trauma Centers; D014947:Wounds and Injuries / Q000097:blood* / Q000145:classification / Q000150:complications
chemical_list: D001779:Blood Coagulation Factors; D011486:Protein C