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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：mélanie petapermal, Master degree
- 電話番号：+590 0590934667
- メール：melanie.petapermal@chu-guadeloupe.fr
研究場所
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Les Abymes、グアドループ、97159
- CHU de la Guadeloupe
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コンタクト：
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コンタクト：
- mélanie petapermal
- 電話番号：0590934667
- メール：melanie.petapermal@chu-guadeloupe.fr
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主任研究者：
- Maryse ETIENNE JULAN, MD
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Bobigny、フランス、93000
- Hôpital Avicenne
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コンタクト：
- Sylvain Lejeune, MD PhD
- メール：sylvain.le-jeune@aphp.fr
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主任研究者：
- sylvain lejeune, MD PhD
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
Patients with sickle cell disease and the HbSS or HbSC genotype recruited from the participating study centers in Guadeloupe or Bobigny
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：COHORT
- 時間の展望：CROSS_SECTIONAL
コホートと介入
グループ/コホート |
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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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Endogenous thrombin potential (ETP)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Lag time of thrombin generation
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
捜査官
- スタディディレクター：Véronique Baccini, MD PhD、chu de la guadeloupe
- 主任研究者：Sylvain Lejeune, MD PhD、Centre de Référence Maladies Rares Adulte de Bobigny " Drépanocytose / syndromes drépanocytaires majeurs " de l'hôpital Avicenne
- 主任研究者：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
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CHUG_RIPH2_2026/01
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