Dr De Paepe acknowledges that this work was supported by a grant nr.# G.0171.05N from the Fund for Scientific Research, Flanders to ADP and a Methusalem grant # BOF08/01M01108 from the Flemish Government and the Ghent University to ADP. FM is a postdoctoral research fellow from the Fund for Scientific Research, Flanders. Dr Shovlin acknowledges funding support from the British Heart Foundation, donations from British HHT patients and the NIHR Biomedical Research Centre Funding Scheme. “
“Summary. An antibody response to therapeutically administered factor VIII (FVIII) can occur in up to 30% of patients with haemophilia,
resulting in the production of inhibitors that neutralize FVIII coagulant activity. Immune tolerance induction (ITI) therapy can be used to eradicate inhibitors PLX3397 cost in these Olaparib solubility dmso patients, allowing them to continue with factor replacement therapy. Patients with inhibitors (prior to initiation
of ITI, while on ITI or those who fail ITI) experience more difficulty in treating bleeds than those patients who do not develop inhibitors. Increasingly, prophylaxis with bypassing therapy is being employed in patients who develop inhibitors. Two bypassing agents, a plasma-derived activated prothrombin complex concentrate [aPCC (FEIBA®; Baxter AG, Vienna, Austria)] and NovoSeven® [recombinant factor VIIa (rFVIIa); NovoNordisk, Denmark] are potentially available for prophylaxis in patients with haemophilia who have developed inhibitors. Results from recent retrospective studies demonstrate the efficacy and safety of both aPCC and rFVIIa in decreasing the frequency of bleeding episodes in patients with haemophilia and inhibitors. In this article, we highlight 4-Aminobutyrate aminotransferase a number of ongoing studies that aim to identify patients who should be placed on prophylaxis with bypassing agents. The development of neutralizing antibodies (inhibitors) to replacement factors [factor VIII (FVIII) or factor IX (FIX)] [1] can be devastating
for patients with haemophilia [2]. The burden of orthopaedic complications and the impact on quality of life (QoL) are more severe in haemophilic patients who have developed inhibitors than in those without inhibitors [3]. Incidence estimates suggest that inhibitors develop in 20–30% of patients with haemophilia A and in 5% of patients with haemophilia B [4], and although these patients do not experience more bleeding episodes than those without inhibitors, haemostasis is more difficult to control when bleeding does occur [2]. Inhibitors may be transient or resolve with immune tolerance induction (ITI) therapy [5], the initiation of which aims to eradicate inhibitors with the purpose of permitting a return to prophylaxis with FVIII or FIX replacement. Since the introduction of ITI, the success rate achieved with various regimens has typically been between 60% and 80% [6].