Vascular Abnormalities and Bleeding Diathesis

Endothelial Dysfunction Leads to Bleeding Diathesis

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.

Study Overview

• Status: Completed
• Conditions: 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.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • UH Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A specific Family

Description

Inclusion criteria:

- members of the family

Exclusion criteria:

- patient who refused to participate

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Affected family members
Affected PM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
platelet count	automatic count of platelet	1 day
platelet aggregation	automated assay using adenosine diphosphate (ADP), arachidonic acid (AA) agonists	1 day
VWF (von Willebrand factor)	activity/antigen levels measurements	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VWF mutimerization status	multimer distribution	1 day
immunostaining of platelets	fixed platelet studies coverslips are challenged with a panel of primary antibodies for immunofluorescence staining	2 to 3 days

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Muriel GIANSILY-BLAIZOT, UH Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: mucocutaneous bleeding; surgery bleeding outcomes
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease Attributes; Hematologic Diseases; Hemostatic Disorders; Blood Coagulation Disorders; Hemorrhage; Disease Susceptibility; Hemorrhagic Disorders
• Other Study ID Numbers: RECHMPL20_0471

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: NC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No