Comparison of the effect of plasma-derived and recombinant human FVIIa in vitro and in a rabbit model

Both purified plasma-derived FVIIa (pFVIIa) and recombinant FVIIa (rFVIIa) were shown to shorten the in vitro APTT in haemophilic plasma significantly. After addition of 3.8 micrograms/ml of pFVIIa or rFVIIa, corresponding to 110-140 FVII U/ml, the APTT was normalized in both haemophilia A and haemophilia B plasma. Furthermore, the prolonged APTT in plasma from a patient with acquired inhibitors against FVIII:C was normalized by addition of pFVIIa or rFVIIa in vitro. These results indicate an alternative pathway to the FVII or FVIIa-TF complex formation involving phospholipids (present in the APTT reagent). No signs of systemic activation of the coagulation system in rabbits following infusion of 500, 1000, 5000 U pFVIIa or rFVIIa/kg body weight, corresponding to about 150 micrograms/kg body weight, were seen. This corresponded to 2-3 times the clinical dose of FVIIa.