Recombinant factor VIIa reduces bleeding after blunt liver injury in coagulopathic, hypofibrinogenaemic pigs

Abstract

BackgroundRecombinant factor VIIa (rFVIIa) has been successfully used in various clinical conditions to treat severe coagulopathy, but its efficacy may be affected by the underlying conditions. We therefore investigated the efficacy of rFVIIa treatment under conditions of hypofibrinogenaemia in a pig model of blunt liver injury. MethodsSevere haemodilution was instigated in four groups of seven anaesthetized pigs. Before inflicting liver injury, animals were assigned to receive either 70 mg kg−1 fibrinogen (fibrinogen group) or placebo (control group). Thirty seconds after injury, rFVIIa (180 µg kg−1) (rFVIIa and fibrinogen+rFVIIa groups) or vehicle (control and fibrinogen groups) was administered. Haemodynamic variables, coagulation parameters, and blood loss were monitored for 2 h. Histology was examined to evaluate the presence of thrombi and the consistency of liver injury. ResultsAt the end of the observation period, total blood loss [median (range)] decreased in all intervention groups [fibrinogen: 1275 (1221–1439) ml, P=0.036; rFVIIa: 966 (923–1136) ml, P=0.008; fibrinogen+rFVIIa: 678 (475–756) ml, P=0.008] when compared with control animals [blood loss: 1752 (1735–2221) ml]. The mortality rate in the control group was 100%, whereas only 42% of fibrinogen-substituted animals died (P=0.023). All animals treated with rFVIIa or fibrinogen+rFVIIa (P<0.001) survived and no signs of thromboembolism were observed. ConclusionsrFVIIa under conditions of hypofibrinogenaemia exhibited a positive impact on coagulation parameters and a reduction in blood loss. These effects were significantly improved after prior substitution with fibrinogen.