Thromboelastographic assessment of the efficacy of rFVIIa in vitro and in vivo

Abstract

Haemorrhage is a leading cause of death in both the military and civilian environs and blood loss from sites which are not easily accessible or do not lend themselves to direct physical compression to reduce blood loss contribute hugely to the haemorrhage mortality rate, particularly in the face of delay before surgical intervention. A number of agents aimed at controlling non-compressible haemorrhage are currently under evaluation, including activated recombinant factor Vila (rFVIIa), a drug injected intravenously. rFVIIa is an attractive option to control blood loss in this population of patients since the drug can be injected at any site, the effects of rFVIIa targeted to where they are required. A number of clinical case reports and case series have demonstrated a beneficial effect of rFVIIa in trauma victims, when used as a last resort. These anecdotal reports are yet to be corroborated by adequately powered clinical trials. Animal studies have yielded conflicting results, some demonstrating a clear effect of rFVIIa on survival and others finding no benefit, or effect only on parameters such as blood product usage. Further research is required to firmly establish the efficacy of rFVIIa in trauma patients. The in vivo animal study from which blood samples for the present study were obtained provided a model of haemorrhage followed by progressive haemodilution associated with intravenous fluid resuscitation. The main aim of the in vitro study that forms the experimental work for this thesis was to compare the ability of rFVIIa with placebo to enhance clotting under the effects of progressive haemodiltion. A further aim was to establish whether a second dose of rFVIIa under these conditions had any effect. The study utilised an established technique called thromboelastography (TEG) to compare clotting in blood samples treated in vitro with rFVIIa and placebo.