Batric Popovic1, Faiez Zannad2, Huguette Louis3, Isabelle Clerc-Urmès4, Cécile Lakomy3, Sébastien Gibot5, Cécile V Denis6, Patrick Lacolley3, Véronique Regnault7. 1. Université de Lorraine, INSERM, DCAC, F-54000 Nancy, France; CHRU de Nancy, Department of Cardiology, Nancy, France. 2. Université de Lorraine, INSERM, DCAC, F-54000 Nancy, France; CHRU de Nancy, Department of Cardiology, Nancy, France; Centre d'Investigations Cliniques Plurithematique 1433, Nancy, France. 3. Université de Lorraine, INSERM, DCAC, F-54000 Nancy, France. 4. CHRU de Nancy, Platform of Clinical Research Facility PARC, Unit MDS, Nancy, France. 5. Université de Lorraine, INSERM, DCAC, F-54000 Nancy, France; CHRU de Nancy, Intensive Care Unit, Nancy, France. 6. INSERM, UMR_S 1176, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France. 7. Université de Lorraine, INSERM, DCAC, F-54000 Nancy, France. Electronic address: veronique.regnault@inserm.fr.
Abstract
BACKGROUND: Subjects with heart failure (HF) are at higher risk of developing thrombosis. We investigated whether endothelium activation and inflammation induce a prothrombotic biological profile in patients with acute decompensated HF (ADHF) and sinus rhythm. METHODS: Our prospective study included 34 ADHF patients, 30 patients with stable chronic HF (CHF) and 30 control inpatients without HF. In vitro thrombin generation and its downregulation by activated protein C (APC) was monitored by calibrated automated thrombography at hospital admission, at the day of discharge and after discharge, following at least six weeks of clinical stability. Circulating endothelium-derived extracellular vesicles (eEVs) were quantified by flow cytometry and nucleosomes by ELISA. RESULTS: Thrombin generation is increased and APC sensitivity is decreased independently of platelets in ADHF at admission compared to controls (p < 0.01). Thrombin generation was also increased in CHF but only in the presence of platelets. Plasma markers of endothelium activation (von Willebrand factor, factor VIII, procoagulant eEVs and circulating nucleosomes) and the ability of plasmas to induce neutrophil extracellular trap formation in control neutrophils are elevated in ADHF at admission compared to controls (p < 0.001). In-hospital prothrombotic changes in ADHF improved significantly at the post-discharge time-point. Circulating nucleosomes were positively correlated with APC sensitivity (p = 0.013) and annexin-V-positive eEVs (p = 0.004). CONCLUSIONS: This proof-of-concept study identified an endothelial-driven hypercoagulable phenotype at the acute phase of decompensated HF contrasting with the platelet-dependent prothrombotic state in CHF. These results highlighted a cross-talk between circulating eEVs and nucleosomes, procoagulant factors and impairment of the APC anticoagulant activity in ADHF.
BACKGROUND: Subjects with heart failure (HF) are at higher risk of developing thrombosis. We investigated whether endothelium activation and inflammation induce a prothrombotic biological profile in patients with acute decompensated HF (ADHF) and sinus rhythm. METHODS: Our prospective study included 34 ADHFpatients, 30 patients with stable chronic HF (CHF) and 30 control inpatients without HF. In vitro thrombin generation and its downregulation by activated protein C (APC) was monitored by calibrated automated thrombography at hospital admission, at the day of discharge and after discharge, following at least six weeks of clinical stability. Circulating endothelium-derived extracellular vesicles (eEVs) were quantified by flow cytometry and nucleosomes by ELISA. RESULTS:Thrombin generation is increased and APC sensitivity is decreased independently of platelets in ADHF at admission compared to controls (p < 0.01). Thrombin generation was also increased in CHF but only in the presence of platelets. Plasma markers of endothelium activation (von Willebrand factor, factor VIII, procoagulant eEVs and circulating nucleosomes) and the ability of plasmas to induce neutrophil extracellular trap formation in control neutrophils are elevated in ADHF at admission compared to controls (p < 0.001). In-hospital prothrombotic changes in ADHF improved significantly at the post-discharge time-point. Circulating nucleosomes were positively correlated with APC sensitivity (p = 0.013) and annexin-V-positive eEVs (p = 0.004). CONCLUSIONS: This proof-of-concept study identified an endothelial-driven hypercoagulable phenotype at the acute phase of decompensated HF contrasting with the platelet-dependent prothrombotic state in CHF. These results highlighted a cross-talk between circulating eEVs and nucleosomes, procoagulant factors and impairment of the APC anticoagulant activity in ADHF.
Authors: Christina Christersson; Tomasz Baron; Frank Flachskampf; Lars Lindhagen; Bertil Lindahl; Agneta Siegbahn Journal: J Cardiovasc Transl Res Date: 2022-06-21 Impact factor: 4.132
Authors: Dominika Klimczak-Tomaniak; Marie de Bakker; Elke Bouwens; K Martijn Akkerhuis; Sara Baart; Dimitris Rizopoulos; Henk Mouthaan; Jan van Ramshorst; Tjeerd Germans; Alina Constantinescu; Olivier Manintveld; Victor Umans; Eric Boersma; Isabella Kardys Journal: Sci Rep Date: 2022-02-18 Impact factor: 4.379