Cardiac Surgery, Cardiopulmonary Bypass, Platelet Activation
Conditions
Keywords
Procoagulant platelets, Platelet lipidomics, Postoperative inflammation, Postoperative bleeding
Brief summary
The PLACARD research project aims to investigate the impact of CPB-induced platelet modifications during cardiac surgery on the post-operative inflammatory response and bleeding complications. Our objectives are to study the impact of CPB on the formation of procoagulant platelets, to assess changes in platelet lipid profile and bioenergetics before, during and after cardiac surgery, and to connect the ex-vivo observations to post-operative clinical and biological parameters of these patients during their stay in cardiovascular intensive care unit.
Detailed description
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: 1. Characterize the impact of CPB on the formation of procoagulant platelets. 2. Assess changes in platelet lipid composition and bioenergetics before, during and after cardiac surgery. 3. 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.
Interventions
BIOLOGICALArterial blood sample
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.
Sponsors
Université Catholique de Louvain
Fonds National de la Recherche Scientifique
Fondation Mont-Godinne
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Procoagulant platelet formation | Throughout the entire study, approximately during 32 months | Ex-vivo flow cytometric assessment of the pourcentage of procoagulant platelet population under basal and stimulated conditions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet lipidomics | Throughout the entire study, approximately during 32 months | Assessment of the impact of cardiac surgery and cardiopulmonary bypass on platelet lipid metabolism. Pourcentage of patients with platelet Acety-CoA Carboxylase phosphorylation. |
| Postoperative bleeding | Throughout the entire study, approximately during 32 months | 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)). |
| Postoperative inflammation | Throughout the entire study, approximately during 32 months | Correlation between the ex-vivo primary outcomes and biological postoperative parameters (C-reactive protein). |
| Postoperative platelet function | Throughout the entire study, approximately during 32 months | Correlation between the ex-vivo primary outcomes and biological postoperative parameters (platelet aggregometry results). |
| Postoperative coagulation | Throughout the entire study, approximately during 32 months | Correlation between the ex-vivo primary outcomes and biological postoperative parameters (thromboelastography and standard coagulation results (INR, aPTT, Fibrinogen)). |
Countries
Belgium
Contacts
CONTACTChristophe Beauloye, MD, PhD
CONTACTRichard Coulie, MD
Outcome results
None listed