How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors

Abstract

The management of bleeds in patients with haemophilia A or B complicated by inhibitors is complex. Recombinant activated Factor VII (rFVIIa; NovoSeven RT) is an established therapy in these patients. To develop a consensus-based guide on the practical usage of rFVIIa in haemophilia complicated by inhibitors, nine expert haemophilia specialists from Australia and New Zealand developed practice points on the usage of rFVIIa, based on their experience and supported by published data. Practice points were developed for 13 key topics: control of acute bleeding; prophylaxis; surgical prophylaxis; control of breakthrough bleeding during surgery or treatment of acute bleeds; paediatric use; use in elderly; intracranial haemorrhage; immune tolerance induction; difficult bleeds; clinical monitoring of therapy; laboratory monitoring of therapy; concomitant antifibrinolytic medication; practical dosing. Access to home therapy with rFVIIa is important in allowing patients to administer treatment early in bleed management. In adults, 90-120 μg/kg is the favoured starting dose in most settings. Initial dosing using 90-180 μg/kg is recommended for children due to the effect of age on the pharmacokinetics of rFVIIa. In the management of acute bleeds, 2-hourly dosing is appropriate until bleeding is controlled, with concomitant antifibrinolytic medication unless contraindicated. The practice points provide guidance on the usage of rFVIIa for all clinicians involved in the management of haemophilia complicated by inhibitors.

Combined administration of FVIII and rFVIIa improves haemostasis in haemophilia A patients with high‐responding inhibitors – a thrombin generation‐guided pilot study

“…Our study has proved the safety of combined FVIII–rFVIIa therapy, as treatment was well‐tolerated by young children and adults and no clinical thrombosis or DIC evolved. With regard to efficacy, indeed 70–90% efficacy of rFVIIa therapy alone has previously been reported for mild to moderate hemarthrosis treatment of inhibitor patients , however, most patients required two to three repeated doses of 90 μg kg −1 whereas in our study 90% response was documented following a single combined dose (the median rFVIIa dose being 90 μg kg −1 ) only. Therapy has been applied to mild or moderate bleeds as target joint bleeds were also successfully treated by repeated doses, and minor surgeries were similarly handed with no complications.…”

Spanish Consensus Guidelines on prophylaxis with bypassing agents in patients with haemophilia and inhibitors

“…Importantly, secondary prophylaxis has also been shown to reduce the impact of bleeding events on daily life activities in these patients, both in terms of reducing school or work absenteeism and hospitalisations. Results of these studies have been the subject of recent reviews (19)(20)(21)(34)(35)(36)(37)(38)(39). As far as primary prophylaxis goes, the evidence is very limited, but the objective would be similar to that in patients without inhibitors, i. e. to prevent life-threatening and joint or recurrent bleedings and to avoid haemophilic arthropathy.…”

Pulmonary embolus in a haemophilia patient

“…However, variable responses to the individual bypassing agents are seen within an individual and between patients. 1 Currently there is no effective assay to assess a patient's responsiveness to these therapies. 1 We present a 6-year-old boy with SHA complicated by a FVIII inhibitor, who required extraction of six teeth.…”

“…1 Currently there is no effective assay to assess a patient's responsiveness to these therapies. 1 We present a 6-year-old boy with SHA complicated by a FVIII inhibitor, who required extraction of six teeth. Following the dental extractions haemostasis was obtained with FEIBA 50 U/kg 12 hourly and tranexamic acid mouthwash.…”