title: Prolonged prothrombin time after recombinant activated factor VII therapy in critically bleeding trauma patients is associated with adverse outcomes.
abstract: BACKGROUND
  In trauma patients with significant hemorrhage, it is hypothesized that failure to normalize prothrombin time (PT) after recombinant activated factor VII (rFVIIa) treatment predicts poor clinical outcomes and potentially indicates a need for additional therapeutic interventions.
  
  
  METHODS
  To assess the value of PT to predict outcomes after rFVIIa or placebo therapy, we performed a post hoc analysis of data from 169 severely injured, critically bleeding trauma patients who had 1-hour postdose PT measurements from two randomized clinical trials. Baseline characteristics and outcome parameters were compared between subjects with 1-hour postdose PT >or=18 seconds and PT <18 seconds.
  
  
  RESULTS
  In rFVIIa-treated subjects, prolonged postdose PT values >or=18 seconds were associated with significantly higher 24-hour mortality (60% vs. 3%; p < 0.001) and 30-day mortality, increased incidence of massive transfusion, and fewer intensive care unit-free days compared with postdose PT values <18 seconds. Recombinant rFVIIa-treated subjects with postdose PT >or=18 seconds had significantly lower baseline hemoglobin levels, fibrinogen levels, and platelet counts than subjects with postdose PT values <18 seconds even though they received similar amounts of blood products before rFVIIa dosing. Placebo-treated subjects with postdose PT >or=18 seconds had significantly increased incidence of massive transfusion, significantly decreased intensive care unit-free days, and significantly lower levels of fibrinogen and platelets at baseline compared with subjects with postdose PT values <18 seconds.
  
  
  CONCLUSIONS
  The presence of prolonged PT after rFVIIa or placebo therapy was associated with poor clinical outcomes. Because subjects with postdosing PT >or=18 seconds had low levels of hemoglobin, fibrinogen, and platelets, this group may benefit from additional blood component therapy.
authors.affiliation: US Army Institute of Surgical Research, BAMC-Fort Sam Houston, Texas, USA.
authors.forename: Neil R
authors.initials: NR
authors.lastname: McMullin
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wade
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
authors.forename: Tina G
authors.initials: TG
authors.lastname: Nielsen
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Bruno
authors.initials: B
authors.lastname: Riou
authors.forename: Sandro B
authors.initials: SB
authors.lastname: Rizoli
authors.forename: Yoram
authors.initials: Y
authors.lastname: Kluger
authors.forename: Philip I T
authors.initials: PI
authors.lastname: Choong
authors.forename: Brian
authors.initials: B
authors.lastname: Warren
authors.forename: Bartholomew J
authors.initials: BJ
authors.lastname: Tortella
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Boffard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011237:Predictive Value of Tests; D011517:Prothrombin Time / Q000401:mortality; D012372:ROC Curve; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000097:blood* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D005340:Fibrinogen; D015942:Factor VIIa