Recombinant activated factor VII as an adjunctive therapy for bleeding control in severe trauma patients with coagulopathy: subgroup analysis from two randomized trials.
BACKGROUND
We conducted a post-hoc analysis on the effect of recombinant factor VIIa (rFVIIa) on coagulopathic patients from two randomized, placebo-controlled, double-blind trials of rFVIIa as an adjunctive therapy for bleeding in patients with severe trauma.


METHODS
Blunt and penetrating trauma patients were randomly assigned to rFVIIa (200 + 100 + 100 microg/kg) at 0, 1, and 3 hours after transfusion of 8 units of red blood cells (RBCs) or to placebo. Subjects were monitored for 48 hours post-dosing and followed for 30 days. Coagulopathy was retrospectively defined as transfusion of fresh frozen plasma (FFP) (>1 unit of FFP per 4 units of RBCs), FFP in addition to whole blood, and transfusion of platelets and/or cryoprecipitate.


RESULTS
Sixty rFVIIa-treated and 76 placebo subjects were retrospectively identified as being coagulopathic. No significant differences were noted in baseline characteristics. The rFVIIa-treated coagulopathic subgroup consumed significantly less blood product: RBC transfusion decreased by 2.6 units for the whole study population (P = 0.02) and by 3.5 units among patients surviving more than 48 hours (P < 0.001). Transfusion of FFP (1,400 versus 660 ml, P < 0.01), platelet (300 versus 100 ml, P = 0.01), and massive transfusions (29% versus 6%, P < 0.01) also dropped significantly. rFVIIa reduced multi-organ failure and/or acute respiratory distress syndrome in the coagulopathic patients (3% versus 20%, P = 0.004), whereas thromboembolic events were equally present in both groups (3% versus 4%, P = 1.00).


CONCLUSIONS
Coagulopathic trauma patients appear to derive particular benefit from early adjunctive rFVIIa therapy.
Rizoli
Sandro B
SB
Department of Surgery and Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, M4N 3M5 Canada. sandro.rizoli@sw.ca
Boffard
Kenneth D
KD
Riou
Bruno
B
Warren
Brian
B
Iau
Philip
P
Kluger
Yoram
Y
Rossaint
Rolf
R
Tillinger
Michael
M
D000328:Adult; D001778:Blood Coagulation Disorders / Q000188:drug therapy*; D001803:Blood Transfusion; D004311:Double-Blind Method; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000150:complications*
D011994:Recombinant Proteins; D015942:Factor VIIa