Haemophilia A and B are the most frequent inherited bleeding disorders. Together with von Willebrand disease, a defect of primary haemostasis associated with a secondary defect in coagulation factor VIII (FVIII), these disorders include 95% to 97% of all the inherited deficiencies of coagulation factors 1. The other 3%-5% are represented by rare bleeding disorders (RBDs), the less common inherited disorders, including deficiency of fibrinogen, prothrombin, factors V, combined V+VIII, VII, X, XI and XIII. These disorders are inherited in an autosomal recessive manner and their prevalence is approximately 1:500 000 or less in the general population of western countries.
The natural history and spectrum of clinical manifestations of RBDs are not well established, since few centres in the world have the opportunity to see a significant number of these rare patients. There are a few RBD databases available on-line but most of them are national or focus only on molecular or clinical aspects of a single deficiency. None systematically collects clinical, phenotypic, genotypic and treatment features of RBDs.
In 2004, at the 50th Scientific and Standardisation Committee (SSC) meeting organised by the International Society of Thrombosis and Haemostasis held in Venice, an SSC working group on "Rare Bleeding Disorders" was established within the framework of the FVIII/IX subcommittee. The main goals of this group are:
To establish and implement an International Database of Rare Bleeding Disorders that will allow for comprehensive analysis of the distribution of patients affected by RBDs in each region of the world, increasing the knowledge of the clinical and therapeutic aspects of these deficiencies To identify available drugs for replacement therapy for each RBD in different regions of the world with the final aim of monitoring and overhauling world-wide drug production, cost and distribution to encourage the development of drugs, particularly for deficiencies with no available therapeutic treatment To meet these goals, the International Database on Rare Bleeding Disorders (RBDD) was developed to efficiently collect and extract existing data on RBDs. The database contains clinical, genetic and therapeutic information, including clinical manifestations, type of bleeding, type of deficiency, complications, treatment, and prenatal diagnosis. In order to identify potential collaborators worldwide, an on-line
website was set up to facilitate networking of Haemophilia Centres around the world.
Preliminary information on distribution of affected patients in four major areas of the world (North, Central and South America, Europe, Asia and Africa), available treatment in these centres and reported problems in treatment availability have been evaluated using a specific questionnaire. The results of this analysis are published on the website. Further information concerning clinical manifestations and management of patients will be collected by a future analysis of individual information obtained for each specific disease. The results could be useful to understanding the gaps in our knowledge of clinical manifestations, treatment practices and patient outcome. This analysis will be important for determining scientific, regulatory and other challenges to be faced in the development of novel products and in the design of further required clinical trials, in order to finally provide evidence-based guidelines for diagnosis and management of patients affected by RBDs.
