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Genomics of Fibrin Clot Structure in Patients With Constitutional Dysfibrinogenemia

NCT05233384 · Status: ACTIVE_NOT_RECRUITING · Type: OBSERVATIONAL · Enrollment: 70

Last updated 2024-06-18

No results posted yet for this study

Summary

Hereditary dysfibrinogenemia results from monoallelic mutation in one of the fibrinogen genes (FGA, FGB, FGG). The spectrum of molecular abnormalities is broad, leading to several subtypes of coagulation disorders with specific biological and clinical features. The correlation between the genotype and the phenotype is poor, and the clinical course of patients, from major bleeding to recurrent thromboses, is unpredictable. Fibrin clot structure is a determinant of the risk of thrombosis in cardiovascular diseases. In all individuals, fibrin networks define the propensity of clot to be more resistant to removal or, on the contrary, susceptible to fragmentation leading to bleeding complications. Besides fibrinogen variants, other relatively common genetic polymorphisms in coagulation and fibrinolytic pathways may affect the fibrin clot structure and therefore act as modifiers of the blood clot function.

In this proposal, the investigators will analyze properties (polymerization, fibrinolysis, viscoelastic properties, permeation) and ultrastructure (size, number, packaging, architecture of fibrin fiber by confocal microscopy and scanning electron microscopy) of plasma-based clots in relation to the presence of genetic modifiers (polymorphisms). Polymorphisms will be detected using a whole exome sequencing (WES) in a selected panel of genes of the coagulation and fibrinolytic pathways. The gene panel of 28 genes will include the three fibrinogen genes plus 25 potential modifier genes including F5, F2, PAI-1, PROCR and MTHFR. The overall clot phenotype will be correlated to the presence of prothrombotic polymorphisms and to the patient's clinical phenotype. The investigators plan to include about 100 patients with dysfibrinogenemia. The combination of integrative hemostasis models with genetic dataset will provide a global view of the patient's individual hemostatic profile. This may allow to better predict the clinical outcome and help provide a more personalized therapeutic strategy and precision medicine. In addition, the development of models allowing a reliable global assessment of fibrin clot architecture will be the basis for further research in other acquired diseases involving thrombotic or bleeding events.

Conditions

  • Hereditary Dysfibrinogenemia

Interventions

BIOLOGICAL

Blood test

For each patient included, this study will involve the collection of 20 ml of blood during a blood test carried out as part of routine care. One EDTA tube (4,5 ml) will be withdrawn and frozen for genetic testing. 15 ml of citrated blood sample (3 to 5 tubes, depending on the used tubes) are necessary for the study of fibrin clot structure. Citrated tubes will be double centrifugated and frozen (-80°C) according to "Groupe Français d'Études sur l'Hémostase et la thrombose" guidelines (centrifugation protocol: 1500 to 2000g at least 15min, or 2000 to 2500g at least 10min with an intermediate decantation).

Sponsors & Collaborators

  • University Hospital, Clermont-Ferrand

    lead OTHER

Principal Investigators

  • Aurélien LEBRETON · University Hospital, Clermont-Ferrand

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-07-28
Primary Completion
2024-05-15
Completion
2024-12-31

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05233384 on ClinicalTrials.gov