Use of recombinant activated factor VII in trauma

In this article we describe the current use of recombinant activated factor VII (rFVIIa; NovoSeven®) in trauma patients. Emphasis is placed on current uses as defined by key studies, efficacy data, and safety data. Most published studies in trauma patients are retrospective case studies and reports, although an international, double-blind, randomized, controlled, phase II study has been conducted that reported on the efficacy of rFVIIa in reducing the amount of blood products transfused in blunt trauma patients. That study demonstrated the efficacy and safety profile of this hemostatic agent as compared with placebo as adjunctive therapy in the management of severe bleeding associated with trauma. Further prospective, randomized, and placebo-controlled clinical trials will yield more information on the role of rFVIIa in the management of traumatic bleeding. Introduction Trauma mortality has been described to have a trimodal or bimodal distribution [1-4]. Of trauma deaths 50% occur at the scene of injury because of massive head injury or exsanguination [3,4]. There is then a second peak, which represents 30% of the deaths that occur early, half of which are due to uncontrollable hemorrhage [3,4]. A third phase of later deaths, related to multiple organ failure (MOF) associated with prolonged shock, massive transfusion, and infection [5,6], is also seen, although improvements in trauma care have seen figures fall. Life-threatening traumatic hemorrhage that occurs is often due to surgical and coagulopathic bleeding. Successful surgical control of bleeding has been assisted by the evolution and refinement of angioembolization [5,6]. The coagulopathy of trauma has remained problematic and its etiology is multifactorial, involving hypothermia, acidosis, consumption of clotting factors, and dilution [7,8]. If a patient develops the lethal triad of hypothermia, acidosis, and coagulopathy, then surgical control is less likely to be effective alone [9]. Coagulopathy in trauma may also be due to traumatic brain injury, fat embolus syndrome, or pre-existing comorbidities requiring oral anticoagulation. Attempts to minimize transfusion of blood and blood products have led clinicians to look at alternate means of restoring hemostasis [10]. Use of recombinant activated factor VII in trauma Recombinant activated factor VII (rFVIIa; NovoSeven®; Novo Nordisk A/S, Bagsværd, Denmark) has been used to control life-threatening traumatic bleeding that has been uncorrected by other means. rFVIIa acts to amplify coagulation at the local site of injury where tissue factor and phospholipids are exposed, accelerating the tissue factor-dependent pathway and generating a thrombin burst along with platelet surface interactions [11,12]. The first published account of the use of rFVIIa in trauma was a case report from Kenet and coworkers [13] published in 1999, documenting the first successful use of rVIIa in a soldier with traumatic coagulopathy following a high velocity gunshot wound to the inferior vena cava. The first case report in the USA was that by O’Neill and coworkers [14] published in 2002, which described the use of rFVIIa in a patient sustaining multiple stab wounds who was transfused with more than 100 units of blood before receiving a single dose of rFVIIa. This patient’s coagulopathy did resolve, but she later succumbed to sepsis. In 2001 Martinowitz and coworkers [15] reported on the use of rFVIIa in experimental grade V liver trauma in coagulopathic swine. In this experimental model, in which liver packing was combined with rFVIIa treatment, post-treatment blood loss was significantly less and the prothrombin time decreased Review Recombinant activated factor VIIa and hemostasis in critical care: a focus on trauma Alicia M Mohr1, John B Holcomb2, Richard P Dutton3 and Jacques Duranteau4 1Assistant Professor of Surgery, Department of Surgery, New Jersey Medical School, Newark, New Jersey, USA 2COL, MC, US Army, Chief, Trauma Division, Trauma Consultant for The Surgeon General Commander, US Army Institute of Surgical Research, Fort Sam Houston, Texas, USA 3Associate Professor of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA 4Professor, Departement d’Anesthesie-Reanimation, Hopital de Bicetre, Le Kremlin-Bicetre, France Corresponding author: Alicia M Mohr, [email protected] Published online: 7 October 2005 Critical Care 2005, 9(Suppl 5):S37-S42 (DOI 10.1186/cc3784) This article is online at http://ccforum.com/supplements/9/S5/S37 © 2005 BioMed Central Ltd