As explained in the brief summary, whole exome sequencing (WES) of DNA was performed in a family of four patients suffering from unexplained excessive bleeding. It allowed the identification of a variant which segregated to family members with bleeding diathesis. Firstly, in vitro, functional analyses were performed in primary human endothelial cells. Then, in-vivo analysis have to be performed on affected patients.~The four related patients suffering from excessive bleeding have been followed clinically in France for many years. During the follow-up of three of these affected patients, biological studies are planned.~Biological assays include:~Conventional assessment of primary haemostasis: platelet count, platelet aggregation, functional and antigen measurement of von Willebrand factor.~Specific testing: Von Willebrand factor multimeric profile, immunolabeling of platelets.~Conventional assessment is part of the conventional follow-up of patients with inherited bleeding disorder. It will not require any additional blood sample. For specific testing and after informed consent, fresh blood samples of patients will be collected in 1/10 volume of acid-citrate-dextrose and centrifuged for 10 min at 200 g to obtain Platelet-rich plasma (PRP) for functional analysis of platelets and Platelet-poor plasma for the multimerization state of von Willebrand factor. Then, the results will be compared to the in-vitro findings.
Inherited bleeding disorders (IBD) consist of a heterogeneous group of diseases including coagulation and/or platelets defects and more rarely vascular dysfunctions. A family of four patients suffering from unexplained excessive bleeding has been followed clinically in France for many years. Recently, whole exome sequencing (WES) of DNA allowed the identification of a heterozygous genetic variant which segregated to family members with bleeding diathesis. The aim of the study was to better characterize the phenotype by studying VWF and platelets in affected family members ultimately contributing to the pathogenesis of a bleeding diathesis.