Megakaryocyte Heterogeneity in Sickle Cell Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Sickle Cell Disease (SCD). Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Guadeloupe
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Characterization of Megakaryocytic Subpopulations and the "Immune" Phenotype of Platelets of the Sickle Cell Disease Patient
Overview
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.
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.
Primary outcome measures
- proportion of immune megakaryocytes CD148+CD48+ in bone marrow [Time frame: 24 months]
Secondary outcome measures (1)
- platelet phenotype [Time frame: 24 months]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Other
Study locations
Guadeloupe · 1 center
- Chu de La Guadeloupe — Pointe-à-Pitre
Identifiers
NCT: NCT06850337 · PAP_RIPH2_2024/04 · 2024-A01093-44