Videomicroscopy for the Prediction of Bleeding in Constitutional Haemorrhagic Diseases

Study Overview
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Brief Summary
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In Willebrand disease, there is currently no test available to identify non-invasively patients with a high risk of bleeding from angiodysplasias The study propose to use a sublingual capillary bed analysis by video-microscopy, a sensitive, reproducible and non-invasive technique, to assess whether sublingual capillary density is predictive of hemorrhagic risk for patients with von Willebrand disease.

Official Title
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Interest of Sublingual Videomicroscopy for the Prediction of Bleeding in Von Willebrand Disease and Other Constitutional Haemorrhagic Diseases

Conditions
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Von Willebrand Diseases, Glanzmann Thrombasthenia

Intervention / Treatment
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* Device: Sublingual videomicroscopy
* Biological: blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient with a significant form of von Willebrand disease (according to the inclusion criteria of the Willebrand Disease French Reference Center), a Glanzmann Thrombasthenia, a moderate to severe Haemophilia A or a woman carrying the hemophilia gene Social insured patient Exclusion Criteria: Minor patient Refusal of consent Person benefiting from a system of legal protection Pregnant patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with haemorrhagic disease<br>Patients with von Willebrand disease or Patients with Glanzmann Thrombasthenia | Device: Sublingual videomicroscopy<br>* Measurement of sublingual capillary density by video microscopy<br>Biological: blood sample<br>* Collection of citrate tubes of 5 mL at baseline and at 36 months<br>|
| Other: Control group<br>Patients with moderate or severe hemophilia A or women carrying the hemophilia gene | Device: Sublingual videomicroscopy<br>* Measurement of sublingual capillary density by video microscopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the ROC curve from Sublingual capillary density to inclusion for the event existence of at least a clinically significant haemorrhage |  | at 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sublingual capillary density | To compare the sublingual capillary density of patients with von Willebrand disease to that of 3 other groups of patients: with a severe form of hemophilia A with a moderate form of hemophilia A women carrying the hemophilia gene | At baseline | 
| qualitative abnormalities of sublingual capillaries (capillary haemorrhage, capillary dystrophy) | presence or absence of qualitative abnormalities | At baseline and at 3 years | 
| delta of Sublingual capillary density increase |  | between inclusion and end of study (at 3 years) | 
| ISTH-BAT haemorrhagic score (International Society on Thrombosis and Hemostasis - Bleeding Assessment Tool) | ISTH-BAT is a questionnaire minimum score ranges from 0 to 10 whereas maximum score ranges from 20 to 30 | At baseline, at 3 years | 
| delta of increase of ISTH-BAT haemorrhagic score | ISTH-BAT is a questionnaire minimum score ranges from 0 to 10 whereas maximum score ranges from 20 to 30 | between inclusion and end of study (at 3 years) | 
| plasma levels of proangiogenic markers | dosage of angiopoietin-1, angiopoetin-2 (pg/mL) measured by ELISA | at inclusion and end-of-study visits(at 3 years) | 
| plasma levels of galectine | galectin-1 and galectin-3 measured by ELISA | at inclusion and end-of-study visits(at 3 years) | 
| plasma levels of VEGF | Concentration (pg/ml) of Vascular Endothelial Growth Factor (VEGF) in blood measured by ELISA | at inclusion and end-of-study visits(at 3 years) | 
| delta of increase in plasma levels of all proangiogenic markers |  | At inclusion and end of study (at 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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constitutional haemorrhagic diseases, Videomicroscopy, prediction, bleeding, Videomicroscopy, prediction, bleeding