Phenotypic and Transcriptomic Description of Megakaryocytes in Sickle Cell Patient

Recruiting

• Conditions: Sickle Cell Disease (SCD)

• Registration Number: NCT06887907
• Lead Sponsor: University Hospital, Toulouse

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).

Study Timeline

• Status Verified: 2025-03
• Study Start: 2025-03-13
• Study First Submitted: 2025-03-14
• Study First Submitted QC: 2025-03-14
• Last Update Submitted: 2025-03-14
• Study First Posted: 2025-03-20
• Last Update Posted: 2025-03-20
• Primary Completion: 2027-04-01
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Description of circulant megakaryocytes	12 months	Phenotypic and transcriptomic description of circulant megakaryocytes in sickle cell patient

Trial Locations

Locations (1)

CHU de Toulouse; 🇫🇷 Toulouse, France