Role of Inflammasome in Platelet Activation in Sickle Cell Disease Patient

Completed

• Conditions: Sickle Cell Disease

• Registration Number: NCT06986837
• Lead Sponsor: Centre Hospitalier Universitaire de la Guadeloupe

Brief Summary

Sickle cell disease is characterized by chronic hemolytic anemia, painful crisis called vaso-occlusive crisis and chronic inflammation. Activated platelets of Sickle cell disease patients participated to both chronic inflammation and painful vaso-occlusive crisis .

The main aim of this study is to characterize the contribution of Nucleotide-binding domain Leucine Rich repeat containing Protein 3 inflammasome in platelets' activation in Sickle cell disease and to connect platelet activation, inflammation and sickle cell disease complication.

Detailed Description

During inflammation, platelets are activated through different cell signaling pathways, all of them leading to P selectin expression. Platelets activated by intravascular hemolysis (hemoglobin and heme) and High-Mobility Group Box protein 1 released by activated cells, participate to vaso-occlusive crisis occurrence through an increase of pro-inflammatory state. Toll-Like Receptor 4, expressed at the membrane of platelets, and the Nucleotide-binding domain Leucine Rich repeat containing Protein 3. inflammasome expressed by platelets, may also be involved in these processes. In addition, platelets express Bruton Tyrosine Kinase which could be activated through Nucleotide-binding domain Leucine Rich repeat containing Protein 3 and Toll-Like Receptor 4 pathways. These platelet cell signaling activation pathways related to inflammation, not well explored in Sickle cell disease, could connect platelet activation, inflammation and vaso-occlusive crisis . In this study, the collaborators will determine Nucleotide-binding domain Leucine Rich repeat containing Protein 3 activation state in platelets of Sickle cell disease patients.

Sickle cell disease patients will be recruited in the active file of the sickle cell center of Guadeloupe. Two groups of patients will be constituted: SS patients and SC patients. The control group will be patients who came for screening at the sickle cell center of Guadeloupe (University hospital of Guadeloupe, Pointe à Pitre).

Only one blood collection will be realized during the annual follow up visit of the patients and during the screening visit for the controls.

Study Timeline

• Study Start: 2020-10-14
• Primary Completion: 2023-02-05
• Study Completion: 2024-04-20
• Status Verified: 2025-05
• Study First Submitted: 2025-05-06
• Study First Submitted QC: 2025-05-22
• Last Update Submitted: 2025-05-22
• Study First Posted: 2025-05-23
• Last Update Posted: 2025-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

• patients with SS or SC Sickle cell disease
• diagnosis of SCD performed by electrophoresis or HPLC in a reference laboratory for hemoglobinopathies
• clinically in a steady state at inclusion (without complication in the last month and without transfusion in the three last months)
• patient followed up for Sickle cell disease at the sickle cell center of Guadeloupe (University hospital of Guadeloupe, Pointe à Pitre)
• patients who will provide written informed consent in accordance with the Declaration of Helsinki
• patients affiliated to national social security

Exclusion Criteria

• • patients with hemoglobinopathy other than SS and SC Sickle cell disease
• patients with a transfusion therapy or on bleeding therapy for less than three months
• patients no affiliated to national social security
• pregnant or breastfeeding patients
• patients who will not provide written informed consent in accordance with the Declaration of Helsinki

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
platelets' Nucleotide-binding domain Leucine Rich repeat containing Protein 3 activation	Baseline	flow cytometry

Trial Locations

Locations (1)

Chu de La Guadeloupe; 🇬🇵 Pointe-à-Pitre, Guadeloupe