Phenotypic and Transcriptomic Description of Megakaryocytes in Sickle Cell Patient

NCT ID: NCT06887907

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-03-13
• Study Completion Date: 2028-04-01

Brief Summary

Sickle cell disease is the most common inherited blood disorder in the world. Chronic hemolysis induces platelet activation and chronic inflammation. Platelets and megakaryocyte, as medullar platelets precursors, are known to play a role in innate immunity. Little is known about the role of megakaryocytes at basal state and during acute complication in sickle cell disease patients. The aim of this study is to evaluate the role of megakaryocytes in sickle cell disease.

Detailed Description

Sickle cell disease is the most common inherited blood disorder worldwide. It is a hemoglobinopathy characterized by a chronic hemolysis, vaso-occlusion, endotheliopathy, coagulation activation and chronic inflammation. It is a multisystemic disease leading to acute (Vaso-occlusive crisis, acute chest syndrome) and chronic complications with multiorgan damage. Platelets are activated and release pro-inflammatory mediators in sickle cell disease patients. Less is known about megakaryocytes, precursors of platelets, in sickle cell disease. Nevertheless, it recently has been shown that megakaryocytes, are also produced in the lung and can displayed a pro-inflammatory transcriptomic signature depending on local conditions. An increase in pulmonary megakaryocytes has been described in vascular diseases associated with excessive coagulation, in acute respiratory distress syndrome, and infections demonstrated that during severe SARS-CoV2 pneumonia, there was an increase in circulating megakaryocytes characterized by a pro-inflammatory transcriptomic signature. Acute chest syndrome represents the first cause of mortality in patients with sickle cell disease, characterized by an acute respiratory failure whose pathophysiology includes vaso-occlusive phenomena, infection and inflammation. Given a pro-inflammatory and pro-thrombotic state in sickle cell disease, particularly in acute chest syndrome, we suggest that the megakaryocyte may be involved in the pathophysiology of sickle cell disease. The aim of this study is to evaluate the role of megakaryocytes by peripheral blood sampling from 10 sickle cell disease patients at rest since at least 1 year, 10 sickle cell disease patients at rest and 20 patients during acute complications (10 sickle cell disease patients during vaso-occlusive crises, 10 sickle cell disease patients during acute chest syndrome).

Conditions

Sickle Cell Disease (SCD)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Sickle cell disease patients at rest since at least 1 year

Patient at steady state since at least 1 year

No interventions assigned to this group

Sickle cell disease patients at rest

Patient at steady state (without crises)

No interventions assigned to this group

Vaso-occlusive crisis

Sickle cell disease patients during vaso-occlusive crisis

No interventions assigned to this group

Acute chest syndrome

Sickle cell disease patients during acute chest syndrome

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Sickle cell disease SS or S-béta° thalassemia
• Patient at steady state since at least 1 year or at steady state (without crisis), or during vaso-occlusive crisis or during acute chest syndrome
• Age > 18 years old

Exclusion Criteria

• Patient objects to take part in the study Hematologic disorder (leukemia, myeloma, myelodysplasic syndrome, myeloproliferative syndrome)
• Immune thrombocytopenia, Immunosuppressive or anti-inflammatory (biotherapies, corticosteroids, non steroidal anti-inflammatories drugs) Page 12 sur 23
• Anti-platelets agents
• Red blood cell exchange or transfusion < 3 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre COUGOUL, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

CHU de Toulouse

Toulouse, France, France

Site Status: RECRUITING

Countries

France

Central Contacts

Pierre COUGOUL, MD

Role: CONTACT

cougoul.pierre@iuct-oncopole.fr

0531156265 ext. 33

Facility Contacts

Pierre COUGOUL, MD

Role: primary

cougoul.pierre@iuct-oncopole.fr

0531156265 ext. 33

Other Identifiers

RC31/25/0017

Identifier Type: -

Identifier Source: org_study_id