Megakaryocyte Heterogeneity in Sickle Cell Disease (MegaDrep)

Characterization of Megakaryocytic Subpopulations and the "Immune" Phenotype of Platelets of the Sickle Cell Disease Patient

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, painful crisis called vaso-occlusive crisis (VOC) and chronic inflammation. Activated platelets of SCD patients participated to both chronic inflammation and painful VOC. Platelets are anucleated cells from the fragmentation of megakaryocytes in bone marrow.

The main aim of this study is to characterize the distribution of the different megakaryocyte subpopulations of sickle cell disease patients SS and SC and in particular the "immune" megakaryocytes CD148+CD48+ and to compare it with the platelet phenotype.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease (SCD)

Detailed Description

Platelets are activated in all sickle cell disease patients at baseline with higher expression of selective P (CD62P). Platelets provide a major function in primary hemostasis by the formation of the platelet clot and also participate in coagulation through the formation of an electro-negative phospholipid surface essential to the enzymes of the coagulation cascade. It is now known that platelets are also immune cells that are able to secrete pro-inflammatory cytokines (TGF beta, IFN gamma), that they express certain Toll-like receptors (TLR4) and the inflammasome NLRP3 leading to the activation of caspase-1. Several teams, including ours, have shown that inflammasome and/or caspase-1 can be activated in an infectious context, particularly viral (dengue fever, COVID) and inflammatory (chronic inflammatory bowel diseases, etc.).

Platelets are anucleated cells from the fragmentation of megakaryocytes. Their protein profile is therefore the result of bone marrow differentiation of megakaryocytes. Recently, it has been shown a cellular heterogeneity within megakaryocytes including immune megakaryocytes whose proportion can significantly increase in stress and inflammation condition. It is not clear whether these immune megakaryocytes that could behave as antigen-presenting cells are capable of producing blood platelets.

We wonder whether sickle cell disease patients have a different proportion of these immune megakaryocytes compared to healthy subjects and whether their activated blood platelets carry specific markers of these immune megakaryocytes.

SCD 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 composed of patients who come for hip or knee replacement and do not suffer from chronic disease. Only one blood and bone marrow collection will be realized during the study.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Valérie Hamony Soter; Phone Number: +590590934677; Email: valerie.soter@chu-guadeloupe.fr
• Study Contact Backup: Name: melanie petapermal; Phone Number: +590590934667; Email: melanie.petapermal@chu-guadeloupe.fr

Study Locations

• Guadeloupe
  • Pointe-à-Pitre, Guadeloupe, 97159
    • CHU de la Guadeloupe
    • Contact: Valérie Hamony Soter; Phone Number: +590590934677; Email: valerie.soter@chu-guadeloupe.fr
    • Contact: Mélanie Petapermal; Email: melanie.petapermal@chu-guadeloupe.fr
    • Principal Investigator: Veronique Baccini, MD PhD
    • Sub-Investigator: Maryse Etienne-Julan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with sockle celle disease are patients who come for their disease. Control group are patients who come at the University hospital of Guadeloupe (Pointe à Pitre), for hip or knee replacement and will do not suffer from chronic disease.

Description

Inclusion Criteria:

• patients with SS or SC SCD
• diagnosis of SCD performed by electrophoresis or HPLC in a reference laboratory for hemoglobinopathies
• patients older than 18 years at inclusion
• 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 SCD 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
• the control group (AA subjects) will be patients older than 18 years old who come at the University hospital of Guadeloupe, (Pointe à Pitre) for hip or knee replacement and will do not suffer from chronic disease.

Exclusion Criteria:

• patients younger than 18 years old
• patients with hemoglobinopathy other than SS and SC SCD
• 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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
SS patients; patients with SS sickle cell disease
SC patients; patients with SC sickle cell disease
control group AA; patient without sickle cell disease (AA hemoglobin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of immune megakaryocytes CD148+CD48+ in bone marrow	The primary outcome will be the evaluation of the proportion of immune megakaryocytes CD148+CD48+ in bone marrow of sickle cell disease patients in comparison to control group.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
platelet phenotype	The secondary outcomes are to compare the platelet phenotype between the three groups of patients, including the proportion of CD148+CD48+ platelets, to study the activation of this platelet subpopulation (expression of CD62P) and establish whether there is a relationship between the proportion of immune megakaryocytes in the bone marrow and the proportion of CD148+CD48+ platelets in the blood.	24 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de la Guadeloupe
• Investigators: Study Chair: Veronique Baccini, MD PhD, CHU de la Guadeloupe

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 24, 2025
• First Submitted That Met QC Criteria: February 24, 2025
• First Posted (Actual): February 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: platelets; sickle cell disease; immune megakaryocytes; CD48; CD148
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: PAP_RIPH2_2024/04; 2024-A01093-44 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No