Abstract
BackgroundRecombinant factor VIIa (rFVIIa) is registered for use in haemophilia with inhibitors and other rare bleeding disorders, but has also been used in various other clinical conditions to terminate life-threatening bleeding. Underlying conditions (e.g. coagulopathy) and dosing may affect treatment efficacy. The objective of the present study was to evaluate the impact of increasing doses of rFVIIa on blood loss and coagulation assays in haemodiluted and hypothermic pigs undergoing blunt liver injury.MethodsA grade III blunt liver injury was induced in 28 pigs after 70% haemodilution and cooling to 32.6–33.4°C. Ten minutes after trauma, animals randomly received placebo or 90, 180 or 360 μg/kg rFVIIa. Global coagulation parameters, thromboelastometry (TEM) and plasma thrombin generation (TG) were determined at different time points during the observation period of 120 minutes.ResultsTotal blood loss was significantly lower following 90 μg/kg rFVIIa (1206 [1138–1470] mL) relative to placebo (2677 [2337–3068] mL; p<0.05), with no increased effect with higher dose levels of rFVIIa. Following trauma and haemodilution, coagulation was impaired relative to baseline in both TEM and TG analysis. At 60 and 120 minutes after trauma, TEM variables improved in the rFVIIa-treated animals compared with the placebo group. Similarly, rFVIIa improved coagulation kinetics in TG. As was observed with blood loss, no significant effect between different rFVIIa dose levels was found in TEM or TG. Macro- and microscopic post-mortem examination did not reveal any signs of thromboembolic events.ConclusionEarly administration of 90 μg/kg rFVIIa reduced blood loss in pigs undergoing blunt liver injury even after severe haemodilution and hypothermia, with no further effect of higher dose levels. Coagulation assays showed impaired coagulation in coagulopathic animals, with a dose-independent improvement in animals treated with rFVIIa.
Highlights
Trauma is often associated with coagulopathy, which complicates the control of bleeding and leads to a four-fold increase in the risk of mortality [1,2]
At 60 and 120 minutes after trauma, Thromboelastometry analysis (TEM) variables improved in the Recombinant factor VIIa (rFVIIa)-treated animals compared with the placebo group
Therapy with purified or recombinant coagulation factors, such as fibrinogen, prothrombin complex concentrates (PCCs) and recombinant activated coagulation factor VII, has been shown to reduce severe bleeding and may be used as an approach to restore coagulation in traumatic injury complicated by coagulopathy [4,5,6]. rFVIIa was initially developed to treat haemophilia patients with inhibitory antibodies [7] and approved indications for its use have been expanded to include other rare bleeding disorders
Summary
Trauma is often associated with coagulopathy, which complicates the control of bleeding and leads to a four-fold increase in the risk of mortality [1,2]. Coagulopathy of trauma has multiple causes, including tissue injury, shock, hypothermia, haemodilution, inflammation and acidosis [1,2]. RFVIIa was initially developed to treat haemophilia patients with inhibitory antibodies [7] and approved indications for its use have been expanded to include other rare bleeding disorders. The potential effect of rFVIIa may be affected by dosing regimen and the presence of severe haemodilution, hypothermia and acidosis [10,11,12]. The objective of the present study was to evaluate the impact of increasing doses of rFVIIa on blood loss and coagulation assays in haemodiluted and hypothermic pigs undergoing blunt liver injury
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
