title: Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway?
abstract: OBJECTIVE
  Coagulopathy following major trauma is conventionally attributed to activation and consumption of coagulation factors. Recent studies have identified an acute coagulopathy present on admission that is independent of injury severity. We hypothesized that early coagulopathy is due to tissue hypoperfusion, and investigated derangements in coagulation associated with this.
  
  
  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, fibrinogen, thrombomodulin, protein C, plasminogen activator inhibitor-1, and D-dimers. Base deficit (BD) was used as a measure of tissue hypoperfusion.
  
  
  RESULTS
  A total of 208 patients were enrolled. Patients without tissue hypoperfusion were not coagulopathic, irrespective of the amount of thrombin generated. Prolongation of the partial thromboplastin and prothrombin times was only observed with an increased BD. An increasing BD was associated with high soluble thrombomodulin and low protein C levels. Low protein C levels were associated with prolongation of the partial thromboplastin and prothrombin times and hyperfibrinolysis with low levels of plasminogen activator inhibitor-1 and high D-dimer levels. High thrombomodulin and low protein C levels were significantly associated with increased mortality, blood transfusion requirements, acute renal injury, and reduced ventilator-free days.
  
  
  CONCLUSIONS
  Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.
authors: Department of Surgery, University of California at San Francisco, San Francisco, CA, USA. karim@trauma.org
authors: Karim
authors: K
authors: Brohi
authors: Mitchell J
authors: MJ
authors: Cohen
authors: Michael T
authors: MT
authors: Ganter
authors: Michael A
authors: MA
authors: Matthay
authors: Robert C
authors: RC
authors: Mackersie
authors: Jean-François
authors: JF
authors: Pittet
mesh_terms: D000208:Acute Disease; D000328:Adult; D001778:Blood Coagulation Disorders / Q000209:etiology*; D001779:Blood Coagulation Factors / Q000378:metabolism; D001780:Blood Coagulation Tests; D015331:Cohort Studies; D005260:Female; D006801:Humans; D020896:Hypovolemia / Q000097:blood / Q000150:complications*; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism*; D018180:Thrombomodulin / Q000097:blood*; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications*
chemical_list: D001779:Blood Coagulation Factors; D011486:Protein C; D018180:Thrombomodulin