Cell-derived microvesicles in infective endocarditis: Role in diagnosis and potential for risk stratification at hospital admission.

OBJECTIVES: To characterize the plasmatic profile of cell-derived microvesicles (MVs) at diagnosis and during the treatment of patients with infective endocarditis (IE). METHODS: Blood samples from 57 patients with IE were obtained on 3 consecutive moments: upon admission (T0), at 2 weeks (T1), and at the end of treatment (T2), and were compared with 22 patients with other bacterial infections. MPs were measured by flow cytometry and labeled for specific cell markers of CD45 (leukocytes), CD66b (neutrophils), CD14 (monocytes), CD41a (platelets), CD51 (endothelial cells), CD3 (T lymphocyte) and CD235a (erythrocytes). RESULTS: MVs from platelets (pltMVs), leukocytes (leukMVs), neutrophils (neutMVs), monocytes (monoMVs) and lymphocytes (lymphMVs) were significantly more elevated in the patients with IE, compared to the patients with other bacterial infections, despite comparable age, sex, blood counts and C-reactive protein levels. MVs values revealed a relatively stable pattern over time in IE, except for a significant increase in leukMVs and neutMVs in T1. LeukMVs (p = 0.011), neutMVs (p = 0.010), monoMVs (p = 0.016) and lymphMVs (p = 0.020), measured at admission, were significantly higher in IE patients that died during hospitalization in comparison with those that survived. In a multivariable analyses, the levels of neutMVs remained as an independent factor associated with mortality (odds ratio 2.203; 95% confidence interval 1.217 - 3.988; p = 0.009), adjustment for heart failure during the treatment. CONCLUSIONS: Plasma levels of pltMVs, leukMVs, neutMVs, monoMVs and lymphMVs were significantly more elevated in patients with IE than in patients with other bacterial infections at hospital admission. Furthermore, neutMVs at admission have been identified as an independent predictor of mortality in patients with IE. Thus, cell derived MPs may become an important tool in the differential diagnosis and mortality risk assessment early in the course of IE suspected cases.

Outcomes of infective endocarditis in the current era: Early predictors of a poor prognosis.

BACKGROUND: The early identification of patients at risk of complications of infective endocarditis (IE) using parameters obtained as part of routine practice is essential for guiding clinical decision-making. This study aimed to identify a parameter at hospital admission that predicts the outcome, adding value to other well-known factors of a poor prognosis in IE. METHODS: Two hundred and three patients with IE were included in this study. Clinical evaluation, echocardiography, blood cultures, and routine laboratory tests were performed at hospital admission. The endpoint was in-hospital mortality. RESULTS: The mean age of the patients was 48.2±16.6 years; 62% were male and 38% had rheumatic heart disease. During treatment, cardiac surgery was performed in 111 patients (55%), and the overall in-hospital mortality rate was 32%. In the multivariable analysis, the independent predictors of death were age (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.02-1.13), C-reactive protein (CRP) at hospital admission (OR 1.12, 95% CI 1.04-1.21), length of the vegetation at diagnosis (OR 1.15, 95% CI 1.03-1.28), development of heart failure (OR 6.43, 95% CI 2.14-19.33), and embolic events during antimicrobial therapy (OR 12.14, 95% CI 2.11-71.89). CONCLUSIONS: An elevated CRP level at hospital admission and vegetation length at diagnosis were strong predictors of in-hospital mortality in IE, independent of other prognostic parameters, specifically taking into account patient characteristics and complications during therapy.

Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies.

Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that occurs prior to platelet accumulation (i.e. the classical first wave of hemostasis). These three waves of hemostasis, in the event of atherosclerotic plaque rupture, may turn pathogenic, and cause uncontrolled vessel occlusion and thrombotic disorders (e.g. heart attack and stroke). Current anti-platelet therapies have significantly reduced cardiovascular mortality, however, on-treatment thrombotic events, thrombocytopenia, and bleeding complications are still major concerns that continue to motivate innovation and drive therapeutic advances. Emerging evidence has brought platelet adhesion molecules back into the spotlight as targets for the development of novel anti-thrombotic agents. These potential antiplatelet targets mainly include the platelet receptors glycoprotein (GP) Ib-IX-V complex, ß3 integrins (αIIb subunit and PSI domain of ß3 subunit) and GPVI. Numerous efforts have been made aiming to balance the efficacy of inhibiting thrombosis without compromising hemostasis. This mini-review will update the mechanisms of thrombosis and the current state of antiplatelet therapies, and will focus on platelet adhesion molecules and the novel anti-thrombotic therapies that target them.