Special lectures in haemophilia management

Abstract

Summary. During the last two decades major advances have been achieved in the management of haemophilia. Modern approaches aimed at preventing the recurrent bleedings and their sequelae have been widely adopted. Major challenges of intensive treatment regimens employed today, such a short half life of haemophilia therapeutics with a need for frequent injections and the risk of inhibitor, encourage further development towards the production of factor concentrates with prolonged efficacy and reduced immunogenicity. Intensive research work on gene therapy aimed at ultimate cure of haemophilia by the restoration of missing factor FVIII (FVIII) and factor IX (FIX) production is ongoing. The current issues of gene therapy and mechanisms, modifying the host immune response to the FVIII and FIX transgene material and the coagulation factors expressed are the topic of the Arosenius lecture by Katherine High. Despite an extensive research on mechanisms leading to inhibitor development, the real reason of these serious complications of haemophilia therapy still remains unclear. Alessandro Gringeri will discuss the immunogenicity of plasma derived FVIII (pd FVIII) and recombinant FVIII (rFVIII) concentrates as one of potential, treatment related, and probably ÔmodifiableÕ risk factors for inhibitor development. The SIPPET study -a new prospective, randomised study aimed to reveal real incidence of inhibitors in patients treated with either pdFVIII or rFVIII will be presented.

The hope and reality of long‐acting hemophilia products

“…In addition, barriers persist limiting the adoption and adherence of effective prophylactic therapy, particularly in the developing world. Standard prophylaxis regimens (using 25–40 IU/kg of FVIII three times per week or 50–100 IU/kg of FIX twice per week) are difficult for some individuals and suboptimal adherence remains a problem [11]. The development of alloantibodies that inhibit the activity of infused replacement products also remains a significant complication [12].…”

Management of bleeding disorders in children

“…Thus, more data are needed, from multivariate analyses of all known risk factors, to corroborate findings from the current analysis of inhibitor development during administration of rFVIII or pdVWF/FVIII in PUPs with haemophilia. The ongoing, randomized, prospective Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) will have appropriate statistical power and is expected to clarify the true incidence of inhibitors in PUPs with haemophilia who are given rFVIII or pdVWF/FVIII [17,18].…”

Haemophilia: provision of factors and novel therapies: World Federation of Hemophilia goals and achievements

“…Gene therapy is considered one of the best hopes for achieving a cure for a broad spectrum of hereditary and acquired diseases, including haemophilia. The success of gene therapy in the preclinical haemophilia arena has been accruing for >15 years and proof of principle that gene therapy works in humans has been established in clinical trials (Murphy & High, 2008; Batorova et al , 2010). Currently, two Phase I/II trials are in progress with liver‐directed adeno‐associated virus (AAV) FIX gene transfer in which two different AAV serotypes are being evaluated (Murphy & High, 2008; Nathwani, 2010a; Nathwani et al , 2010b).…”