Research

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 Rizoli¹ , Kenneth D Boffard² , Bruno Riou³ , Brian Warren⁴ , Philip Iau⁵ , Yoram Kluger⁶ , Rolf Rossaint⁷ , Michael Tillinger⁸ and the NovoSeven® Trauma Study Group

¹Department of Surgery and Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave., Suite H1-71, Toronto, Ontario, M4N 3M5 Canada

²Department of Surgery, Johannesburg Hospital, University of the Witwatersrand, 17 Pallinghurst Road, Parktown, ZA – Johannesburg 2193, South Africa

³Departments of Emergency Medicine and Surgery and Anesthesiology and Critical Care, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, 4 Place Jussieu, 75005, Paris, France

⁴Department of Surgery, Tygerberg Hospital, University of Stellenboch, Fransie van Zyl Avenue, Tygerberg, Bellville 7530 Cape Town, South Africa

⁵Department of Surgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074

⁶Department of General Surgery B, Rambam Medical Centre, 66 Jabotinsky St., Petach Tikvah Bat-Galim, Haifa, 49100, Israel

⁷Department of Anesthesiology, University Clinics, Pauwelsstr. 30, 52057 Aachen, Germany

⁸Medical and Science Department, Novo Nordisk A/S, Novo Alle 2880 Bagsværd, Denmark

author email corresponding author email

Critical Care 2006, 10:R178doi:10.1186/cc5133

Published:	21 December 2006

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 μg/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.