Performance Evaluation of Von Willebrand:Collagen-Binding Assays to Diagnose Von Willebrand Factor Deficiency in Patients With Increased Risk of Bleeding (PERICOLL)

Von Willebrand Disease (VWD) is defined as an inherited bleeding disorder that is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and also binds and stabilizes blood clotting factor VIII (FVIII) in the circulation. The most severe forms of VWD are usually easy to diagnose (obvious hemorrhagic symptoms and major VWF deficiency), whereas the mild forms of the disease are still difficult to confirm. It is indeed reported that about 1% of the population carry mild biological VWF deficiency without any bleeding tendency and any "actual disease". On the contrary, some patients with severe bleeding history can carry a true VWF abnormality, well-confirmed by genetic studies, without any VWF deficiency when evaluated with standard biological methods, such as Ristocetin Cofactor activity (VWF:RCo). However, in these patients, the use of alternative methods, such as PFA-100 (Platelet Fonction Analyzer-100), the study of Factor VIII (FVIII:C) to VWF (FVIII:C/VWF) ratio or the evaluation of VWF activity using more specialized methods such as VWF:CB (VWF-Collagen Binding) assay can detect the VWF deficiency and possible hemorrhagic predisposition.

In this project, the investigators plan to assess the performance of VWF:CB in the diagnosis of VWF deficiency in patients with unexplained bleeding history.

Study Overview

• Status: Completed
• Conditions: Von Willebrand Disease
• Intervention / Treatment: Other: Non interventional study

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21079
    • Dijon University Hospital
  • Nantes, France, 44093
    • Nantes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study plans to enroll 200 patients (100 per Center) in a 2-year period. The recruitment will occur in standard consultation activity of the 2 Hemostasis Centers of Dijon and Nantes. As each Center carries out about 1200 consultations/year, this projection appears as feasible, since a majority of them are induced by hemorrhagic profile. Such a number of patients will allow reliable statistical analysis.

Description

Inclusion Criteria:

• Patient with bleeding history sent to the Hemophilia Treatment Center in Dijon or Nantes University Hospital with abnormal bleeding score (>3 in men and >5 in women
• Patient who has provided a signed consent to participate at this study and for blood sampling
• Affiliation with French social security system

Non-Inclusion Criteria:

• Minors will not be included in the study.
• On-going pregnancy and postpartum period (3 months after delivery)
• Substitutive treatment with coagulation factor concentrates or desmopressin administration within 10 days before sampling.
• Ongoing infectious or inflammatory disease that can modify VWF levels.
• Diagnosis of obvious hemostasis disorder

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Von Willebrand factor levels measured with Von Willebrand factor: Collagen-Binding methods	Deficiency is defined when VWF level is < 50IU/dL, as usually defined by Favaloro E.J. (2000). A composite reference standard (CRS) will be used to improve the imperfect Gold Standard (VWF: RCo). CRS will be defined as being positive if either VWF: RCo, VWF:Ag, PFA-100 or FVIII:C will be positive and negative otherwise.	Up to 1 year

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2017
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: June 2, 2016
• First Submitted That Met QC Criteria: June 6, 2016
• First Posted (Estimate): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: hematology; Willebrand factor deficiency; Willebrand:Collagen-binding
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Von Willebrand Diseases
• Other Study ID Numbers: RC16_0028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No