In recent years, the validation of a new bleeding score in the adult and paediatric population that has been increasingly utilized worldwide, has allowed for a more homogeneous characterization of the bleeding phenotype [19–21]. Such a genetic study is being started through a collaborative consortium that includes several investigators from around the world. Taking advantage of a large collection of recruited individuals with VWD type 1 and also with a mucocutaneous bleeding disorder without a clear aetiology, and many extended families with multiple

cases, the investigators propose to search for causal genes by carrying out a GWAS. This will be done using a multi-stage study design that JQ1 mouse utilizes available patient material to maximize statistical power and efficiency while minimizing cost. An Selleckchem MLN8237 initial genome-wide discovery stage will be carried out in caucasian patients and controls. Two subsequent sequential follow-up stages will test selected candidate association signals, first in a second caucasian case-control cohort and then by family-based association analysis in a large collection of caucasian multiplex families. Finally, an extension stage will test association signals confirmed in the first replication phase in case-control cohorts from several different non-caucasian

ethnic groups or other bleeding cohorts. This multi-stage approach has demonstrated

to provide enough stringency to ‘pick up’ true signals and eliminate false positives. Recent genome-wide association MCE studies have identified several gene variants involved in platelet size and function as well as myocardial infarction and thrombosis [22–24]. However, most variants affecting bleeding phenotypes remain undiscovered. Therefore, this study may provide new genetic variants involved in bleeding. It is expected that with the discovery of genetic determinants of bleeding, the care of patients with these types of disorders will improve not only by the ability of practitioners to determine bleeding risk but also by the potential therapeutic alternatives that will rise as a result of these new findings. Given the recent significant expansion of our knowledge about human genetics, and in particular, of the molecular basis of coagulation factors, we are now in a position to consider the appropriate role for the inclusion of this knowledge into clinical care. Molecular testing for haemostatic disorders requires access to appropriate expertise, which is not typically available in routine clinical haemostasis laboratories. However, the incorporation of tests based on this knowledge can be done quite easily in specialized centres and aid in patient diagnosis and management.