Clinical trial NCT04553172: Vascular Abnormalities and Bleeding Diathesis
Official title: Endothelial Dysfunction Leads to Bleeding Diathesis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bleeding Diathesis
Keywords: mucocutaneous bleeding
surgery bleeding outcomes
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2020-09-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A specific Family

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion criteria:

- members of the family

Exclusion criteria:

- patient who refused to participate

Primary outcomes:
measure: platelet count
timeFrame: 1 day
measure: platelet aggregation
timeFrame: 1 day
measure: VWF (von Willebrand factor)
timeFrame: 1 day
Secondary outcomes:
measure: VWF mutimerization status
timeFrame: 1 day
measure: immunostaining of platelets
timeFrame: 2 to 3 days
Other outcomes:
Locations:
city: Montpellier
country: France
facility: UH Montpellier
Study officials:
affiliation: UH Montpellier
name: Muriel GIANSILY-BLAIZOT
role: PRINCIPAL_INVESTIGATOR
References: