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.