Current use of by‐passing agents in Europe in the management of acute bleeds in patients with haemophilia and inhibitors

Abstract

The ultimate goal of treatment for patients with inhibitory antibodies should be to permanently eradicate the inhibitor by immune tolerance induction therapy (ITI). However, ITI procedures fail in a substantial number of patients and in many countries ITI is not even offered owing to its high cost. How patients with inhibitors are managed in different European countries is evaluated with a special focus on the use of by-passing agents, i.e. recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC), as well as the type of monitoring performed. Investigators from 22 large haemophilia centres participating within the network of the European Haemophilia Therapy Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was routinely used in all centres for both children and adults at dosages ranging from 90 to 250 mug kg(-1) at an interval of 2-4 h. aPCC was used in 85% of the centres in adults and in 25% of the centres in children with haemophilia A at dosages of 50-100 IU kg(-1) every 6-12 h. The corresponding figures for children and adults with haemophilia B were 40% and 15% of the centres, respectively. Higher dosages of both agents were considered in the case of life-threatening bleeds. General recommendations were developed, based on the information provided by the survey. The results clearly indicate the need for well-designed comparative studies to optimize the use of by-passing agents.

Syngeneic transplantation of hematopoietic stem cells that are genetically modified to express factor VIII in platelets restores hemostasis to hemophilia A mice with preexisting FVIII immunity

“…[12][13][14] Infusion of NovoSeven (FVIIa) may also restore hemostasis in patients with inhibitors, but it is more costly because of its short half life and may result in thrombotic complications. [15][16][17] Gene therapy could be an alternative treatment for hemophilia A. There has been substantial progress in gene therapy of hemophilia A in preclinical trials.…”

Ocena poziomu jakości życia chorych na hemofilię

“…Wyeliminowanie inhibitora u pacjentów z hemofilią to główny cel leczenia, ponieważ umożliwia substytucję z uży-ciem standardowych koncentratów krzepnięcia krwi. Prawidłową hemostazę można osiągnąć u pacjentów z inhibitorami o niskim mianie (≤5 j.B./mL) za pomocą wysokich dawek niedoborowego czynnika, jednak u pacjentów o mianie wysokim (>5 j.B./mL) należy stosować preparaty zawierające aktywowane czynniki krzepnięcia [20]. Dostępne obecnie dane wskazują, że aktywowane preparaty omijające inhibitor są bezpieczne i skuteczne w kontrolowaniu krwawień u chorych na hemofilię z inhibitorami.…”

6 Factor VIII Concentrates, Factor VIII/von Willebrand Factor Concentrates, Factor IX Concentrates, Activated Prothrombin Complex Concentrates

“…b) Activated PCC (FEIBA) shall be given as initial dose: up to 100 U/kg body weight and a maintenance dose of up to 100 U/kg body weight twice daily [6,19,28,65].…”

“…c) Alternatively recombinant factor VIIa shall be given, mean initial dose 90 μg/kg body weight or 270 μg/kg body weight as single dose (see section 7.4) [6,28].…”

“…Combination with FEIBA at a dose of up to 50 U/kg body weight twice daily during inhibitor elimination may be used to reduce the bleeding tendency [5,6,28].…”