Recombinant activated factor VII as an adjunctive therapy for bleeding control in severe trauma patients with coagulopathy: subgroup analysis from two randomized trials

Sandro B Rizoli, Kenneth D Boffard, Bruno Riou, Brian Warren, Philip Iau, Yoram Kluger, Rolf Rossaint, Michael Tillinger, NovoSeven Trauma Study Group, Sandro B Rizoli, Kenneth D Boffard, Bruno Riou, Brian Warren, Philip Iau, Yoram Kluger, Rolf Rossaint, Michael Tillinger, NovoSeven Trauma Study Group

Abstract

Introduction: 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).

Conclusion: Coagulopathic trauma patients appear to derive particular benefit from early adjunctive rFVIIa therapy.

Figures

Figure 1
Figure 1
Trial profile. The figure shows the number of penetrating and blunt trauma patients eligible in the two groups (placebo and recombinant activated factor VII [rFVIIa]), the exclusion of patients because of traumatic brain injury (TBI) and insufficient data concerning the coagulopathic state, and the number of patients finally adjudicated to the placebo and rFVIIa analysis. RBC, red blood cells.
Figure 2
Figure 2
Comparison of the proportion of patients (all coagulopathic patients as well as coagulopathic patients surviving more than 48 hours) requiring massive transfusion. Massive transfusion was defined as more than 12 red blood cell (RBC) units within 48 hours of the first dose, which equals more than 20 units of RBCs (inclusive of the 8 pre-dose units) in the placebo and recombinant activated factor VII (rFVIIa) groups.

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