kluger and colleagues   have done us a service with their careful review of outcomes in patients with traumatic brain injury ( tbi ) from a previous factor viia ( fviia ) trauma trial . although the numbers are small , this work will be important in motivating future prospective trials . mortality in this small cohort was greater than in the overall study population , emphasizing the lethality of tbi plus shock . the lack of self - reported thromboembolic events is encouraging and is in accordance with other prospective trials of fviia use , which have suggested that the risk is real but not excessive . also encouraging are the trends in the outcome variables reported , including mortality and organ failure end - points . although none of these are significant in themselves , they are collectively significant in that they all vary in the same way , favoring fviia . traumatic brain injury ( tbi ) is the most common cause of death after trauma , and it is the most difficult to treat . with no ability to repair or replace injured brain tissue , we are reduced to management of symptoms as they develop and often futile efforts to prevent secondary injury from hypoxia , hypotension , hyperglycemia , hyperthermia , electrolyte imbalances , or progressive cerebral edema . this task is especially complex in the polytraumatized patient , because each associated injury  whether treated or ignored  adds to the likelihood of secondary tbi . delayed fracture fixation increases the risk for pulmonary dysfunction , whereas early operative repair exposes the brain to the risks for hypotension , hypoxia , and adverse effects of anesthetic agents . the combination of hemorrhagic shock and severe tbi is especially lethal , with mortality as much as 10 times greater than that for either condition alone . severe tbi causes coagulopathy through a number of mechanical and inflammatory pathways , but the most significant of these is simple consumption . the brain is rich in tissue factor , which is exposed to the circulation in large quantities when the blood - brain barrier is disrupted by trauma . first , the already small quantity of fviia normally found in the circulation is quickly consumed . second , this consumption triggers a strong local anticoagulant response , which can easily become a systemic effect . prolonged prothrombin time is common following severe tbi , even without evidence of systemic blood loss , and is a very strong marker for poor outcome . recombinant fviia therapy for tbi has been enticing to clinicians for the past 5 years . in our own series of patients receiving fviia following trauma  perhaps the largest single center experience in the world tbi is the second leading indication , found in about 150 out of 350 patients . the immediate clinical effect is dramatic and readily observed ; the prothrombin time normalizes rapidly , even with small doses , and surface bleeding from wounds visibly slows . we have also harbored the notion , unproven but physiologically sensible , that fviia will slow the progression of tbi - associated intracranial hemorrhage on both the macroscopic and microscopic levels , and thus reduce the potential for secondary injury . to the extent that hemorrhagic stroke and tbi have similar pathophysiology , early findings with use of fviia in stroke patients tempering the use of fviia in tbi patients has been the cost , the lack of clinical trials addressing this population , and  most importantly  the unknown risk for thromboembolic complications . after retrospectively examining this risk in our own series of patients , we were struck by two things . first , the baseline rate of post - traumatic cerebral infarction is not well understood ; retrospective diagnosis depends on the presence of computed tomography scans with contrast ( unusual in tbi ) or computed tomography scans obtained days to weeks after injury ( when infarcted brain can be identified ) , and also to some degree on the resolution of the scanner used . all of the post - fviia brain infarcts observed in our series occurred in the presence of severe tbi , just as the majority of all of the complications we found occurred at the site of an identified vascular injury . the current worldwide trial of fviia in trauma patients , focused on the treatment of hemorrhagic shock , specifically excludes patients with severe tbi . there is a clear and urgent need to study this population , however , and to study the very wide range of doses currently seeing anecdotal use , all the way from 10 to 15 g / kg in centers such as my own to the 400 g / kg reported on by kluger and coworkers . even a modest improvement in long - term outcomes achieved by early treatment with fviia would have an impact on the population of patients with severe tbi and give us a badly needed arrow for our therapeutic quiver . rd has received research funding and consulting fees from novo nordisk , inc , the manufacturers of fviia and is a member of their international steering committee for trauma trials .
traumatic brain injury is the leading killer after trauma , in part because of coagulopathy . 
 factor viia may be a useful therapy in this setting , depending on the relative risk for thromboembolic complications . 
 kluger and coworkers recently conducted a retrospective review of patients with traumatic brain injury from a previous factor viia and trauma trial . 
 it documents an encouragingly low rate of complications , and should provide a strong incentive to conduct a prospective study of factor viia in patients with severe traumatic brain injury .