Monitoring low dose recombinant factor VIIa therapy in patients with severe factor XI deficiency undergoing surgery

Although factor XI (FXI) concentrate is an effective replacement therapy in severe FXI deficiency without inhibitors, some patients are unwilling to receive it because it is plasma-derived. We report on the use and monitoring of low dose, recombinant factor VIIa (rFVIIa, NovoSeven?), to cover surgery (caesarean section, cholecystectomy and abdominoplasty) in four female patients (FXI:C 2-4 IU/dl, aged 32-51 years) who wished to avoid exposure to plasma. None of our patients had inhibitors to FXI. Our aim was to find the optimal dose of rFVIIa by in vitro spiking of patient samples and to correlate this with the response to rFVIIa in vivo . Prior to surgery, venous blood was collected into sodium citrate with corn trypsin inhibitor and spiked with 0.25-1.0 μg/ml rFVIIa in vitro , equivalent to a 15-70 μg/kg dose of rFVIIa in vivo . Analysis using thromboelastometry and thrombin generation assays, triggered with tissue factor, showed that the thrombin generation assay was insufficiently sensitive to the haemostatic defect in these patients. A concentration of 0.5 μg/ml was as effective as 1.0 μg/ml FVIIa in normalising thromboelastometry in vitro in all four patients. Therefore, patients received 15-30 μg/kg rFVIIa at 2-4 hourly intervals with tranexamic acid 1g every six hours. Post treatment samples were taken at 10-240 minutes and showed initial normalisation of thromboelastometry with gradual return to baseline after 2-4 hours. In conclusion, low-dose rFVIIa therapy was successfully used in four patients with severe FXI deficiency undergoing surgery to prevent bleeding and can be monitored using thromboelastometry.