Study of Constitutional Platelet Disease

NCT04419987 | Unknown

• 1 other identifier: 2019-30
• Study Type: interventional
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief Summary

Platelets are circulating blood cells. They bind to each other and to the wall of the damaged vessel to prevent excessive blood loss. Platelets can be :

• insufficient in number in the case of thrombocytopenia;
• or non-functional in the case of thrombopathy. Constitutional thrombopathies and thrombopenias are rare diseases. Constitutional thrombopenias cause haemorrhage of variable intensity and are sometimes a sign of more serious haematological pathologies. The evolutionary risk of some constitutional thrombopenias is the appearance of myelofibrosis, dysmyelopoiesis or malignant proliferation. While the evolutionary stakes of some thrombopenias and especially syndromic thrombopenias will be more likely to affect other organs (kidney, heart, bones, brain, ...), other constitutional thrombopenias will have few consequences. Their diagnosis will then have the major challenge of distinguishing them from immunological thrombopenias and avoiding the use of inappropriate and sometimes severe treatments (corticosteroids, IV immunoglobulins, immunosuppressants, splenectomy). Mutations in more than forty genes have been identified to date and are responsible for thrombocytopenia. Constitutional thrombopathies are heterogeneous and may involve different platelet constituents. In short, when platelets are stimulated at a lesion site, various soluble or matrix agonists bind to platelet receptors to induce calcium flow, secretion and platelet aggregation at a vascular gap to prevent blood loss. Constitutional thrombopathies are primarily at risk of spontaneous or induced mucocutaneous bleeding. Some thrombopathies are also part of more complex syndromic patterns. In recent decades, considerable progress has been made in the understanding of thrombopathies, enabling them to be better identified. Details have been provided on platelet dysfunctions linked to abnormalities in the processes of granule biogenesis and secretion, and to signalling defects (in particular surface receptor deficiency). Currently, more than thirty genes are the site of autosomal dominant, recessive or X-linked mutations and can be sequenced.

Conditions

Blood Platelet Disease

Outcome Measures

Primary Outcomes (2)

• Adhesion

  Isolated wafers are deposited on substrate coated plates, the wafers adhere to the substrate. Then the number of adherent wafers will be counted by cell imaging. Several substrates will be tested.

  5 years

• Study of platelet protein expression

  A western blot will be made from the platelet lysate, allowing the detection of specific proteins with the help of antibodies directed against the proteins of interest. A semi-quantitative analysis of these proteins will be performed by chemiluminescence.

  5 years

Study Arms (1)

constitutional platelet patholog

EXPERIMENTAL

Patient and relatives having a constitutional platelet pathology

Genetic: draw blood

Interventions

draw blood GENETIC

search for new genetic variations (when the diagnostic exploration will have been non informative) by sequencing exons.

constitutional platelet patholog

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult or minor over 7 years old.
• Patient and relatives with a constitutional platelet pathology (familial thrombocytopenia resulting in a platelet count \< 150 G.L-1 in several family members and/or familial thrombopathy resulting in platelet dysfunction in several members of a family) for which a genetic variation has been demonstrated but whose deleterious nature remains to be confirmed.
• Patient and relatives having a constitutional platelet pathology (familial thrombocytopenia resulting in a platelet count \< 150 G.L-1 in several members of the family and/or familial thrombopathy resulting in platelet dysfunction in several members of a family) for which the genetic diagnosis has not revealed any variation potentially implicated in the pathology.

You may not qualify if:

• Minor under 7 years of age.
• Patient with no platelet pathology.
• Patient with platelet disease: non-chronic, non-familial.
• Patient with a familial platelet disease with a known deleterious mutation.obviously acquired.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Central Study Contacts

Marie-Christine ALESSI

CONTACT

4 91 32 45 06; marie-christine.alessi@univ-amu.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2020
• First Posted: June 9, 2020
• Study Start: July 20, 2020
• Primary Completion: December 20, 2020
• Study Completion: June 1, 2025
• Last Updated: July 9, 2020

Record last verified: 2020-04