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

摘要

Background. Recombinant factor VIIa (rFVIIa) has been successfully used in various clinicalnconditions to treat severe coagulopathy, but its efficacy may be affected by the underlyingnconditions. We therefore investigated the efficacy of rFVIIa treatment under conditions ofnhypofibrinogenaemia in a pig model of blunt liver injury.nMethods. Severe haemodilution was instigated in four groups of seven anaesthetized pigs.nBefore inflicting liver injury, animals were assigned to receive either 70 mg kg21nfibrinogenn(fibrinogen group) or placebo (control group). Thirty seconds after injury, rFVIIa (180 mgnkg21n) (rFVIIa and fibrinogen+rFVIIa groups) or vehicle (control and fibrinogen groups)nwas administered. Haemodynamic variables, coagulation parameters, and blood lossnwere monitored for 2 h. Histology was examined to evaluate the presence of thrombinand the consistency of liver injury.nResults. At the end of the observation period, total blood loss [median (range)] decreased innall intervention groups [fibrinogen: 1275 (1221–1439) ml, P¼0.036; rFVIIa: 966 (923–1136)nml, P¼0.008; fibrinogen+rFVIIa: 678 (475–756) ml, P¼0.008] when compared with controlnanimals [blood loss: 1752 (1735–2221) ml]. The mortality rate in the control group wasn100%, whereas only 42% of fibrinogen-substituted animals died (P¼0.023). All animalsntreated with rFVIIa or fibrinogen+rFVIIa (P,0.001) survived and no signs ofnthromboembolism were observed.nConclusions. rFVIIa under conditions of hypofibrinogenaemia exhibited a positive impact onncoagulation parameters and a reduction in blood loss. These effects were significantlynimproved after prior substitution with fibrinogen.