Clinical trial NCT06887907: Phenotypic and Transcriptomic Description of Megakaryocytes in Sickle Cell Patient
Official title: Phenotypic and Transcriptomic Description of Megakaryocytes in Sickle Cell Patient
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sickle Cell Disease (SCD)
Keywords: Megakaryocyte
Sickle Cell Disease
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2025-03-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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).

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

Primary outcomes:
measure: Description of circulant megakaryocytes
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Pierre COUGOUL, MD
role: PRINCIPAL_INVESTIGATOR
References: