Evaluating and monitoring the efficacy of recombinant activated factor VIIa in patients with haemophilia and inhibitors

Although the use of bypassing agents has dramatically improved the management of haemophilia in patients with inhibitors, questions remain regarding optimal dosing regimens and methodology for monitoring their clinical effectiveness. In this study, we evaluated the efficacy and safety of two different doses of recombinant activated factor VIIa (rFVIIa) in patients with haemophilia and inhibitors and assessed the feasibility of using thromboelastography (TEG) and thrombin generation assays (TGA) for monitoring the response to rFVIIa. Six patients aged 9-49 years with congenital or acquired haemophilia with inhibitors who experienced a total of nine bleeding episodes were included. Seven episodes were treated with conventional rFVIIa dosing (72.7-109.1 μg/kg), and two episodes were treated with a single high-dose regimen (254.6-264.0 μg/kg). Clinical and haemostatic responses were evaluated. Haemostasis was assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT), factor VII coagulant activity (FVII:C), TEG, and TGA. Six out of seven (85.7%) bleeding episodes responded to conventional rFVIIa dosing, and half (50%) responded to the high-dose regimen. No relationships between PT, aPTT, and FVII:C levels and clinical outcome were observed. However, changes in TEG and TGA parameters tended to correspond to clinical response, although large inter-individual variation in rFVIIa efficacy was noted. A good response was seen with rFVIIa in treating acute bleeding episodes in patients with haemophilia and inhibitors. Because changes in TEG and TGA may correlate with clinical outcomes of rFVIIa, TEG and TGA may be useful for monitoring rFVIIa activity in inhibitor-positive haemophilia.