Effect of antiplatelet agents on Escherichia coli sepsis mechanisms: A review

Despite ever-increasing improvements in the prognosis of sepsis, this condition remains a frequent cause of hospitalization and mortality in Western countries. Sepsis exposes the patient to multiple complications, including thrombotic complications, due to the ability of circulating bacteria to activate platelets. One of the bacteria most frequently implicated in sepsis, Escherichia coli, a Gram-negative bacillus, has been described as being capable of inducing platelet activation during sepsis. However, to date, the mechanisms involved in this activation have not been clearly established, due to their multiple characteristics. Many signaling pathways are thought to be involved. At the same time, reports on the use of antiplatelet agents in sepsis to reduce platelet activation have been published, with variable results. To date, their use in sepsis remains controversial. The aim of this review is to summarize the currently available knowledge on the mechanisms of platelet activation secondary to Escherichia coli sepsis, as well as to provide an update on the effects of antiplatelet agents in these pathological circumstances

High levels of circulating leukocyte microparticles are associated with better outcome in acute respiratory distress syndrome

International audienceINTRODUCTION: The current study has addressed the presence and the cellular origin of microparticles (MP) isolated from bronchoalveolar lavage (BAL) fluid and from blood samples from patients with acute respiratory distress syndrome (ARDS). Their prognostic interest was also investigated. METHODS: Fifty-two patients were included within the first 24 hours of ARDS. They were compared to spontaneous breathing (SB) and ventilated control (VC) groups. Bronchoalveolar lavage (BAL) and blood samples were obtained on Day 1 and Day 3 in an ARDS group. Leukocyte microparticles (LeuMP), neutrophil microparticles (NeuMP), endothelial microparticles (EMP), and platelet microparticles (PMP) were measured in arterial blood and in BAL samples by flow cytometry. Mortality from all causes was recorded at Day 28. RESULTS: All MP subpopulations were detected in BAL. However, only LeuMP and NeuMP were elevated in ARDS patients compared to the SB group (P = 0.002 for both). Among ARDS patients, higher levels of LeuMP were detected in blood (Day 1) and in BAL (Day 3) in survivors as compared with the non survivors. Circulating LeuMP >60 elements/microliter detectable on Day 1 of ARDS, was associated with a higher survival rate (odds ratio, 5.26; 95% confidence interval, 1.10 to 24.99; P = 0.037). CONCLUSIONS: The identification of the cellular origin of microparticles at the onset of ARDS has identified LeuMP as a biomarker of prognostic significance. The higher levels of LeuMP in survivors could be associated with a protective role of this MP subpopulation. This hypothesis needs further investigations

056: Biological efficacy of a 600mg loading dose of clopidogrel in ST-elevation myocardial infarction

BackgroundOptimal platelet reactivity (PR) inhibition is critical to prevent thrombotic events in primary percutaneous coronary intervention (PCI). We aimed to determine the relationship between high on-treatment platelet reactivity (HTPR) and ST-elevation myocardial infarction (STEMI) following a 600mg loading dose (LD) of clopidogrel.Methods and resultsWe performed a prospective monocentre study enrolling patients on clopidogrel undergoing PCI. The VASP index was used to assess PR inhibition after clopidogrel LD. HTPR was defined according to the consensus as a VASP index ≥50%. The present study included 833 patients undergoing PCI. Most patients had PCI for an acute coronary syndrome (58.7%). The mean VASP index was 50±23% with a large inter-individual variability (range: 1–94%). Patients with a VASP index ≥50% were significantly older (p=0.03), with a higher BMI (p<0.001), more often diabetic (p=0.03), taking omeprazole (p=0.03), admitted for an ACS and with a high fibrinogen level compared to good responders (VASP<50%). In multivariate analysis BMI, omeprazole use, acute coronary syndrome and high fibrinogen level (p<0.001) remained significantly associated with HTPR. Of importance, in this analysis STEMI was independently associated with HTPR when compared with the other forms of ACS (NSTEMI and unstable angina) with an odd ratio of 2.14 (95% CI: 1.3 –3.5; p=0.003).ConclusionSTEMI is associated with high on-treatment platelet reactivity following 600mg of clopidogrel. The present results suggest that 600mg of clopidogrel may not be able to achieve an optimal PR inhibition in STEMI patients undergoing PCI and more potent drugs may be preferred

039: Platelet reactivity predicts both ischemic and bleeding events at one year follow-up in acute coronary syndome patients receiving prasugrel

There are evidences of a link between platelet reactivity inhibition and thrombotic and bleeding events. We have previously demonstrated that PR after prasugrel loading dose (LD) predicts short-term thrombotic events. We aimed to further investigate the relationship between PR under prasugrel and one-year thrombotic and bleeding events.MethodPatients were prospectively included in this multicentre study if they had a successful PCI for an acute coronary syndrome (ACS) and received prasugrel. Vasodilator-Stimulated Phosphoprotein (VASP index) was measured after prasugrel LD. Endpoint included the rate of thrombotic events (cardiovascular death, myocardial infarction and stent thrombosis) and bleeding events (TIMI) at one year.ResultsThree hundreds and one patients were enrolled. Nine patients (3%) were lost to follow-up at one year. The rates of thrombotic and bleeding events at one year were 7.5 and 6.8% respectively. The mean VASP index after a 60mg LD of prasugrel was 34}23% and 76 patients (25%) were considered as having high on-treatment platelet reactivity (HTPR). Patients with HTPR had a higher rate of thrombotic events compared to good responders (19.7 vs 3.1%;p<0.001). Patients with a minor or major non-CABG related TIMI bleeding had lower PR compared to patients with no bleeding events (21}18 vs 35}23%;p=0.008). In multivariate analysis, the VASP index predicted both thrombotic and bleeding events (OR: 1.44 (95% CI: 1.2–1.72; p<0.001 and 0.75 (95% CI: 0.59–0.96;p=0.024 (respectively, per 10% increase)).ConclusionPlatelet reactivity measurement after prasugrel LD predicts both ischemic and bleedings events at one year follow-up for ACS patients undergoing PCI

Apport du diagnostic in vitro (de la médecine préventive au schéma thérapeutique)

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Iatrogénie et éducation thérapeutique du patient sous antivitamine K à l'officine

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Intérêt du suivi de l'index de phosphorylation de la protéine VASP [Vasodilator Stimulated Phosphoprotein] chez des patients résistants au clopidogrel (étude prospective, randomisée, multicentrique)

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Contribution du rituximab dans le traitement du PTT autoimmun

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality of ACE2 tends to explain why this molecule plays such an important role in the clinical manifestations of coronavirus disease 2019 (COVID-19). At the very start of the pandemic, a publication from our Institute (entitled “ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome”), was one of the first reviews linking COVID-19 to the duplicitous nature of ACE2. However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types. To gain insight into the physiopathology of SARS-CoV-2 infection, it is essential to consider the polymorphism and expression levels of the ACE2 gene (including its alternative isoforms). Over the past 2 years, an impressive amount of new results have come to shed light on the role of ACE2 in the pathophysiology of COVID-19, requiring us to update our analysis. Genetic linkage studies have been reported that highlight a relationship between ACE2 genetic variants and the risk of developing hypertension. Currently, many research efforts are being undertaken to understand the links between ACE2 polymorphism and the severity of COVID-19. In this review, we update the state of knowledge on the polymorphism of ACE2 and its consequences on the susceptibility of individuals to SARS-CoV-2. We also discuss the link between the increase of angiotensin II levels among SARS-CoV-2-infected patients and the development of a cytokine storm associated microvascular injury and obstructive thrombo-inflammatory syndrome, which represent the primary causes of severe forms of COVID-19 and lethality. Finally, we summarize the therapeutic strategies aimed at preventing the severe forms of COVID-19 that target ACE2. Changing paradigms may help improve patients’ therapy

Mélagatran (un nouveau concept dans le domaine des traitements anticoagulants)

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF