Change in Platelet Lipid Metabolism and Procoagulant Phenotype Induced by Cardiopulmonary Bypass. Impact on Postoperative Inflammatory Response and Bleeding Complications During Cardiac Surgery. (PLACARD)
研究概览
详细说明
Cardiac surgery remains associated with high morbidity and mortality despite improvements in peri and post-operative care. Cardiopulmonary bypass (CPB) triggers a sterile inflammatory response, characterized by vascular hyperpermeability, excessive vasodilation, and cardiac arrythmias, i.e. atrial fibrillation. In parallel, major peri-operative bleeding frequently necessitates transfusion of allogeneic blood products. The pathophysiology underlying these complications is multifactorial. Direct contact of blood with the CPB tubing system, combined with ischemia-reperfusion injury, profoundly alters both the inflammatory and haemostatic systems. Among blood components, platelets are particularly vulnerable to CPB-induced alterations. Platelet dysfunction is widely recognized as the main haemostatic defect associated with CPB and a major contributor to post-operative bleeding. Recent findings have demonstrated that platelet lipid metabolism plays a key role in regulating thrombo-inflammatory responses in sepsis. These observations raise the hypothesis that CPB-induced alterations in platelet lipid metabolism may critically modulate the balance between inflammation and haemostasis in cardiac surgery.
The PLACARD project therefore aims to investigate how CPB-induced platelet modifications influence post-operative inflammatory responses and bleeding complications.
Specific objectives:
- Characterize the impact of CPB on the formation of procoagulant platelets.
- Assess changes in platelet lipid composition and bioenergetics before, during and after cardiac surgery.
- Correlate ex-vivo platelet alterations with post-operative clinical outcomes and biological markers during the stay in the cardiovascular intensive care unit.
This project addresses a critical unmet need in cardiac surgery: understanding the mechanistic link between CPB-induced platelet dysfunction and thrombo-inflammatory complications. By focusing on platelet lipid metabolism, a pathway largely unexplored in this context, the project moves beyond traditional platelet function assays. The results are expected to provide fundamental mechanistic insights into procoagulant platelet formation during CPB and may identify novel biomarkers or therapeutic targets to reduce bleeding and inflammatory complications in high-risk surgical patients.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Christophe Beauloye, MD, PhD
- 电话号码：003227642812
- 邮箱：christophe.beauloye@uclouvain.be
研究联系人备份
- 姓名：Richard Coulie, MD
- 邮箱：richard.coulie@uclouvain.be
学习地点
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Brussels、比利时、1200
- Cliniques Universitaires Saint-luc
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接触：
- Christophe Beauloye, MD, PhD
- 电话号码：003227642812
- 邮箱：christophe.beauloye@uclouvain.be
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接触：
- Richard Coulie, MD
- 邮箱：richard.coulie@uclouvain.be
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副研究员：
- Richard Coulie, MD
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副研究员：
- Mona Momeni, MD, PhD
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首席研究员：
- Christophe Beauloye, MD, PhD
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Adult patients (≥ 18 years old) suffering from coronary disease and/or severe valvular dysfunction (mitral or aortic) undergoing elective coronary angiography or cardiac surgery with cardiopulmonary bypass.
Exclusion Criteria:
- Uninterrupted preoperative dual antiplatelet therapy
- Active chronic inflammatory disease
- Recent chemotherapy or immunotherapy (< 3 months)
- Active solid malignancy
- History of hematologic malignancy
- Hemophilia or other coagulopathy
- History of thrombocytopenia (< 100,000 platelets/mm³)
- Recent administration of thrombopoietin receptor agonist or immunoglobulins
- History of thrombopathy, thrombocytosis, or myeloproliferative syndrome
- History of heparin-induced thrombocytopenia (HIT)
- Cirrhosis or hepatic fibrosis (with or without hypersplenism)
- History of splenectomy, regardless of initial indication
- History of systemic autoimmune disease (e.g., systemic lupus erythematosus, scleroderma, antiphospholipid syndrome, systemic vasculitis)
- Recent major surgery (< 3 months)
- Severe renal insufficiency (eGFR ≤ 30 mL/min/m²) with or without dialysis
- Recent or chronic corticosteroid therapy
- Recent acute coronary syndrome, STEMI type (< 3 months)
- Urgent surgery or procedure
- Preoperative hemodynamic instability
学习计划
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Cathlab patients
This group includes patients with coronary disease and/or valvular disease scheduled for elective coronary angiography.
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An arterial blood sample will be obtained at the beginning of the coronary angiography by using the arterial sheat in place, before administration of Heparin.
An arterial blood sample will be obtained via the arterial line before anesthetic induction, 60 minutes after the beginning of cardiopulmonary bypass and 4 hours after the arrival in the intensive care unit
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实验性的：Cardiac surgery patients
This arm includes patients with coronary disease and/or valvular disease scheduled for elective cardiac surgery with cardiopulmonary bypass.
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An arterial blood sample will be obtained at the beginning of the coronary angiography by using the arterial sheat in place, before administration of Heparin.
An arterial blood sample will be obtained via the arterial line before anesthetic induction, 60 minutes after the beginning of cardiopulmonary bypass and 4 hours after the arrival in the intensive care unit
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Procoagulant platelet formation
大体时间：Throughout the entire study, approximately during 32 months
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Ex-vivo flow cytometric assessment of the pourcentage of procoagulant platelet population under basal and stimulated conditions.
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Throughout the entire study, approximately during 32 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Platelet lipidomics
大体时间：Throughout the entire study, approximately during 32 months
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Assessment of the impact of cardiac surgery and cardiopulmonary bypass on platelet lipid metabolism.
Pourcentage of patients with platelet Acety-CoA Carboxylase phosphorylation.
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Throughout the entire study, approximately during 32 months
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Postoperative bleeding
大体时间：Throughout the entire study, approximately during 32 months
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Correlation between the ex-vivo primary outcomes and clinical postoperative parameters (chest drain output (mL) and need for blood transfusion (units of packed red cells, fresh frozen plasma, platelets and fibrinogen)).
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Throughout the entire study, approximately during 32 months
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Postoperative inflammation
大体时间：Throughout the entire study, approximately during 32 months
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Correlation between the ex-vivo primary outcomes and biological postoperative parameters (C-reactive protein).
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Throughout the entire study, approximately during 32 months
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Postoperative platelet function
大体时间：Throughout the entire study, approximately during 32 months
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Correlation between the ex-vivo primary outcomes and biological postoperative parameters (platelet aggregometry results).
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Throughout the entire study, approximately during 32 months
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Postoperative coagulation
大体时间：Throughout the entire study, approximately during 32 months
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Correlation between the ex-vivo primary outcomes and biological postoperative parameters (thromboelastography and standard coagulation results (INR, aPTT, Fibrinogen)).
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Throughout the entire study, approximately during 32 months
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- PLACARD
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
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