Recombinant factor VIIa in trauma patients with the ‘triad of death’ Biswadev Mitra a,b, *, Peter A. Cameron a,b , Michael J. Parr c , Louise Phillips b a Emergency and Trauma Centre, The Alfred Hospital, Melbourne, Australia b Department of Epidemiology and Preventive Medicine, Monash University, Australia c Intensive Care Unit, Liverpool Hospital, University of New South Wales, Sydney, Australia Introduction Major trauma is a leading cause of death with an overall mortality of about 11%. 4,11 Traumatic coagulopathy is present in 20–34% of trauma patients and accounts for at least a four-fold increase in mortality. 3,12,13 When coagulopathy, hypothermia and acidosis are present in major trauma patients, patients have been described as within the ‘triad of death’. 9 Trauma patients presenting to hospital with the ‘triad of death’ have a mortality of 50–60%. 9,17 There has been considerable debate regarding the ‘off-label’ use of recombinant activated factor VIIa (rFVIIa, eptacog alpha, Novoseven). In trauma, effectiveness has not been established. The use of rFVIIa in trauma patients is usually late rescue therapy when conventional damage control resuscitation and surgery has failed to control bleeding. At this stage of trauma resuscitation where uncontrolled bleeding continues, trauma patients are likely to have components of the ‘triad of death’. In vitro studies have shown factor VIIa to work as well in hypothermic conditions as at temperatures of 37 8C. However, acidosis has been shown to severely impair the activity of FVIIa. 14 It has been postulated that the activity of proteases in the coagulation system is dramatically reduced by acidosis and therapeutically administered factor VIIa is not able to overcome the haemostatic defect in such patients. In vivo, hypothermia and acidosis has also been associated with adverse outcome in trauma patients receiving rFVIIa. This has resulted in most clinical guidelines excluding hypothermic and acidotic patients from receiving factor VIIa, further limiting its use in exsanguinating trauma patients. The aim of this study was to investigate the use of rFVIIa in trauma patients with the ‘triad of death’ to identify potential futility. Materials and methods Setting The Australia and New Zealand Haemostasis Registry (ANZHR) collects data from patients without haemophilia treated with rFVIIa at participating hospitals throughout Australia and New Injury, Int. J. Care Injured 43 (2012) 1409–1414 A R T I C L E I N F O Article history: Received 11 November 2010 Received in revised form 24 January 2011 Accepted 31 January 2011 Keywords: Wounds and injuries Factor VIIa Hypothermia Acidosis Blood coagulation disorders Triad of death A B S T R A C T Introduction: The use of recombinant factor VIIa (rFVIIa) in trauma patients is usually part of rescue therapy when haemorrhage and coagulopathy have not responded to conventional treatment. In this scenario, trauma patients are likely to have one or more components of the ‘triad of death’ (coagulopathy, acidosis and hypothermia). The aim of this study was to report on the outcome of trauma patients with the ‘triad of death’ immediately prior to receiving rFVIIa. Materials and methods: Trauma patients receiving rFVIIa with the ‘triad of death’ were identified from the Australia and New Zealand Haemostasis Registry (ANZHR) and included in the study. The ‘triad of death’ was defined as an INR of >1.5, serum pH of <7.2 and a core temperature of <35 8C. Pre-dose clinical signs, investigations, adverse events and outcomes were analysed. Results: There were 2792 patients in the ANZHR, of which 386 were trauma patients and 45 patients had the ‘triad of death’. Patients with the ‘triad of death’ were significantly older and had higher injury severity scores than other trauma patients, with a mortality of 68.9%. Survivors were significantly less acidaemic (p < 0.001) and had significantly less packed red blood cell (PRBC) transfusion prior to rFVIIa administration (p = 0.041) than non-survivors with the triad of death. Discussion: In the face of refractory bleeding, coagulopathy, acidosis and hypothermia following conventional resuscitation, the use of rFVIIa in trauma patients was associated with survival in 31% of patients and may be considered as a management option. Administration of rFVIIa in patients with a pH of <6.91 appears futile. ß 2011 Elsevier Ltd. All rights reserved. * Corresponding author at: Emergency and Trauma Centre, The Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia. Tel.: +61 3 9076 2782; fax: +61 3 9076 2699. E-mail address: b.mitra@alfred.org.au (B. Mitra). Contents lists available at ScienceDirect Injury jo ur n al ho m epag e: ww w.els evier .c om /lo cat e/inju r y 0020–1383/$ – see front matter ß 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2011.01.033