Endothelial Dysfunction Leads to Bleeding Diathesis

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.