Foreword

Abstract

von Willebrand disease (VWD) is probably the most common congenital bleeding disorder while haemophilia, although relatively rare, remains the best characterized. Advances in the prevention and treatment of bleeding episodes in both conditions have translated into improved quality of life and survival across all age groups. However, improved survival does not come without its own side effect. As patients advance in age, several previously unrecognized morbidities continue to manifest. In this supplement, we highlight the most relevant complications in the ageing population and overview current approaches to their management, while realizing areas of unmet needs. The other focus of the supplement is to shed light upon persisting challenges in the prophylactic treatment of bleeding episodes in patients with haemophilia and VWD, within all age groups. Since the middle of the last century, clotting factor replacement for persons with haemophilia has evolved from plasma cryoprecipitate to plasma protein-free recombinant factor. Reactionary focus on pathogen transmission was addressed in the late 1980s with viral reduction measures for plasma-derived clotting factor (pd-CF) and the development of recombinant clotting factor (rCF) concentrates. What has resurfaced is the unsolved dilemma of inhibitor development in a substantial number of individuals with haemophilia A, and possibly a differential inhibitor induction rate among recipients of pd-CF containing von Willebrand factor (VWF) and rCF. In addition, renewed attention on the profile of the inhibitor patient has incriminated genetic predispositions, timing and intensity of exposure to CFs and temporally associated immunological danger signals. Cogent studies to address these questions, in the United States and internationally, include SIPPET, the CDC Inhibitor Study and the Haemophilia Inhibitor Genetics Study (HIGS). In addition, the means by which these inhibitors can be eradicated using ITI procedures are under investigation. Prophylactic treatment has been recommended for children with severe haemophilia in view of its efficacy in reducing the number of bleeds and therefore preventing the development of haemophilic arthropathy. Nonetheless, the ideal age for starting prophylaxis and the optimal dosing schedule, remain unclear. Moreover, the fact that primary prophylactic treatment with clotting factor has dramatically preserved the joints of younger persons with haemophilia brings into question whether the whole of this benefit continues throughout the adult life of haemophilia patients. It is not known whether intensive episodic or prolonged regular prophylaxis contributes to ageing-related disorders, such as ischaemic heart disease or renal disease, or prevents osteoporosis, in persons with haemophilia; a new focus for the community of haemophilia clinicians and scientists to address. Various investigator-initiated studies are underway in the US, keeping in mind that prospective collaborations are necessary to study this important subset of individuals with haemophilia. Plasma-derived concentrates containing both VWF and coagulation factor VIII (FVIII) have been available since the early 1980s for the treatment of severe VWD with proven haemostatic efficacy and safety. Several clinical studies are also ongoing to evaluate the efficacy and safety of novel recombinant products or single VWF replacement without FVIII, and the benefits of prophylactic use in this patient population. Nonetheless, establishing specific management guidelines, while utilizing the longstanding experience from patients with haemophilia, is warranted. A special focus on women affected with VWD is also called for, as they can experience significant gynaecological and obstetrical bleeding episodes that not only affect their physical health but also their psychosocial well-being. The author received an honorarium from Grifols S.A. for participating in the symposium and production of the article. The author thanks Content Ed Net for providing valuable editorial assistance in the preparation of the article; funding for this assistance was provided by Grifols S.A.