Comparison of Thrombin Generation, Platelet Activation and Aggregation Profiles in Patients With Sickle Cell Disease Depending on Their SS or SC Genotype (DrepAgreg) (DrepAgreg)
Comparison of Thrombin Generation, Platelet Activation and Aggregation Profiles in Patients With Sickle Cell Disease Depending on Their SS or SC Genotype
Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, painful crises called vaso-occlusive crises (VOC) and chronic inflammation. Activated platelets from SCD patients contribute to both chronic inflammation and painful VOC. Individuals with the HbSC genotype experience anemia and less severe clinical manifestations than those with the HbSS genotype; however, they are at higher risk of venous thromboembolic events, particularly pulmonary embolism.
This study aims to investigate whether sickle cell patients exhibit different thrombin generation profiles as well as distinct platelet activation and aggregation profiles, depending on their SS or SC genotype.
Visão geral do estudo
Status
Condições
Descrição detalhada
Sickle cell anemia is the most common genetic disease worldwide. It is due to a homozygous mutation in the beta globin gene leading to the production of abnormal hemoglobin S (HbS). This hemoglobin polymerizes and precipitates in the red blood cells (RBCs) under hypoxic conditions, leading to the rigidification of the red blood cells that obstruct the small vessels and are subsequently destroyed. The disease is thus characterized by chronic hemolytic anemia associated with painful vaso-occlusive crises (VOC) and chronic inflammation. The HbSC genotype is associated with anemia and less severe clinical manifestations than the HbSS genotype. However, the risk of venous thromboembolic events, particularly pulmonary embolism, is paradoxically higher. The pathophysiological mechanisms involved in the occurrence of VOC and venous thromboembolic events (VTE) have not been fully elucidated. They involve phenomena of ischemia-reperfusion and complex interactions between the RBC, the endothelium, the leucocytes and the platelets. The sickle RBCs express phosphatidylserine (PS) on their surface, which facilitates their adhesion to other blood cells and their interaction with the endothelium. The release of hemoglobin and free heme into the circulation, along with oxidative stress, induces endothelial activation and dysfunction, as well as vascular inflammation, platelet activation and clotting. Numerous studies have documented the existence of coagulation activation in sickle cell patients during the stable phase of the disease and during VOCs, decreased levels of physiological inhibitors of coagulation and resistance to activated protein C. One of the main mechanisms of coagulation activation in sickle cell patients is increased tissue factor expression on the surface of activated monocytes and endothelial cells. Free heme promotes NETs (neutrophil extracellular traps) formation, which activates the intrinsic coagulation pathway. Moreover, platelets probably play a pivotal role in the thrombo-inflammatory process, coagulation activation, and the occurrence of VOC and VTE. We hypothesize that sickle cell patients may exhibit a different thrombin generation profile as well as distinct platelet activation and reactivity profiles, depending on their SS or SC genotype.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: mélanie petapermal, Master degree
- Número de telefone: +590 0590934667
- E-mail: melanie.petapermal@chu-guadeloupe.fr
Locais de estudo
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Bobigny, França, 93000
- Hôpital Avicenne
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Contato:
- Sylvain Lejeune, MD PhD
- E-mail: sylvain.le-jeune@aphp.fr
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Investigador principal:
- sylvain lejeune, MD PhD
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Les Abymes, Guadalupe, 97159
- CHU de la Guadeloupe
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Contato:
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Contato:
- mélanie petapermal
- Número de telefone: 0590934667
- E-mail: melanie.petapermal@chu-guadeloupe.fr
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Investigador principal:
- Maryse ETIENNE JULAN, MD
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
Patients with sickle cell disease and the HbSS or HbSC genotype recruited from the participating study centers in Guadeloupe or Bobigny
Descrição
Inclusion Criteria:
- SCD patients with SS or SC
- diagnosis of SCD performed by electrophoresis or high-performance liquid chromatography (HPLC) in a reference laboratory for hemoglobinopathies
- patients older than 18 years at inclusion
- clinically in a steady state at inclusion (no complication in the last month and no 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) or at the Adult Rare Diseases Reference Center "Sickle Cell Disease / Major Sickle Cell Syndromes" of the Avicenne hospital in Bobigny.
- patients who will provide written informed consent in accordance with the Declaration of Helsinki
- patients affiliated with national social security
Exclusion Criteria:
- patients younger than 18 years old
- patients with hemoglobinopathy other than SS and SC SCD
- patients who have received transfusion therapy or on bleeding therapy for less than three months
- patients no affiliated with national social security
- pregnant or breastfeeding patients
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Modelos de observação: COHORT
- Perspectivas de Tempo: CROSS_SECTIONAL
Coortes e Intervenções
Grupo / Coorte |
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SS Group
Patients with sickle cell disease and an SS genotype. |
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SC Group
Patients with sickle cell disease and an SC genotype. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Endogenous thrombin potential (ETP)
Prazo: At baseline
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Thrombin generation profiles will be assessed in whole blood, plasma, and platelet-rich plasma. Endogenous thrombin potential will be compared between patients with sickle cell disease and an SS genotype and patients with sickle cell disease and an SC genotype |
At baseline
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Lag time of thrombin generation
Prazo: At baseline
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Thrombin generation will be assessed in whole blood, plasma, and platelet-rich plasma. Lag time will be compared between patients with sickle cell disease and the HbSS genotype and those with the HbSC genotype. |
At baseline
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Time to peak thrombin generation
Prazo: At baseline
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Thrombin generation will be assessed in whole blood, plasma, and platelet-rich plasma. Time to peak will be compared between patients with sickle cell disease and the HbSS genotype and those with the HbSC genotype. |
At baseline
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Peak height of thrombin generation
Prazo: At baseline
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Thrombin generation will be assessed in whole blood, plasma, and platelet-rich plasma. Peak height will be compared between patients with sickle cell disease and the HbSS genotype and those with the HbSC genotype. |
At baseline
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Platelet activation profile
Prazo: At baseline
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Platelet activation profiles will be assessed and compared between patients with sickle cell disease and the HbSS genotype and those with the HbSC genotype. |
At baseline
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Platelet aggregation profile
Prazo: At baseline
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Platelet aggregation profiles will be assessed and compared between patients with sickle cell disease and the HbSS genotype and those with the HbSC genotype. |
At baseline
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Diretor de estudo: Véronique Baccini, MD PhD, chu de la guadeloupe
- Investigador principal: Sylvain Lejeune, MD PhD, Centre de Référence Maladies Rares Adulte de Bobigny " Drépanocytose / syndromes drépanocytaires majeurs " de l'hôpital Avicenne
- Investigador principal: Maryse ETIENNE JULAN, MD, CHU de la Guadeloupe Coordonnateur, Centre de référence des syndromes drépanocytaires majeurs, thalassémies et autres pathologies rares du globule rouge et de l'érythropoïèse
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Doenças Vasculares
- Doenças cardiovasculares
- Doenças Genéticas, Congênitas
- Doenças Hematológicas
- Embolia e Trombose
- Anemia Hemolítica Congênita
- Anemia Hemolítica
- Anemia
- Hemoglobinopatias
- Tromboembolismo
- Doenças e Anormalidades Congênitas, Hereditárias e Neonatais
- Doenças hemic e linfáticas
- Anemia Falciforme
- Tromboembolismo venoso
Outros números de identificação do estudo
- CHUG_RIPH2_2026/01
Plano para dados de participantes individuais (IPD)
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