Phenotypic and Transcriptomic Description of Megakaryocytes in Sickle Cell Patient (MEGADREP)

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.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease (SCD)

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 Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Pierre COUGOUL, MD; Phone Number: 33 0531156265; Email: cougoul.pierre@iuct-oncopole.fr

Study Locations

• France
  • Toulouse, France, 31059
    • Recruiting
    • CHU de Toulouse
    • Contact: Pierre COUGOUL, MD; Phone Number: 33 0531156265; Email: cougoul.pierre@iuct-oncopole.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient from CHU de Toulouse at steady state since at least 1 year or at steady state (without crisis), or during vaso-occlusive crisis or during acute chest syndrome

Description

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 Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Sickle cell disease patients at rest since at least 1 year; Patient at steady state since at least 1 year
Sickle cell disease patients at rest; Patient at steady state (without crises)
Vaso-occlusive crisis; Sickle cell disease patients during vaso-occlusive crisis
Acute chest syndrome; Sickle cell disease patients during acute chest syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of circulant megakaryocytes	Phenotypic and transcriptomic description of circulant megakaryocytes in sickle cell patient	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Pierre Cougoul, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 14, 2025
• First Submitted That Met QC Criteria: March 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Sickle Cell Disease; Megakaryocyte
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: RC31/25/0017

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