Activated factor VII–antithrombin complex predicts mortality in patients with stable coronary artery disease: a cohort study

Abstract

Olivieri O. Activated factor VII-antithrombin complex predicts mortality in patients with stable coronary artery disease: a cohort study.J Thromb Haemost 2016; 14: 655-66. Essentials• Activated factor VII-antithrombin complex (FVIIa-AT) in plasma may reflect tissue factor exposure.• FVIIa-AT levels were assessed in an angiographically controlled coronary artery disease (CAD) cohort.• High FVIIa-AT levels correlated with an increased thrombin generation.• High FVIIa-AT levels were associated with a greater risk of mortality in patients with stable CAD.Summary. Background: Plasma concentration of activated factor VII (FVIIa)-antithrombin (AT) complex has been proposed as an indicator of intravascular exposure of tissue factor. Objectives: The aims of this observational study were to evaluate (i) FVIIa-AT plasma concentration in subjects with or without coronary artery disease (CAD) and (ii) its association with mortality in a prospective cohort of patients with CAD. Methods: FVIIa-AT levels were measured by ELISA in 686 subjects with (n = 546) or without (n = 140) angiographically proven CAD. Subjects with acute coronary syndromes and those taking anticoagulant drugs at the time of enrollment were excluded. CAD patients were followed for total and cardiovascular mortality. Results: There was no difference in FVIIa-AT levels between CAD (84.8 with 95% confidence interval [CI] 80.6-88.2 pmol L -1 ) and CAD-free subjects (83.9 with 95% CI 76.7-92.8 pmol L -1 ). Within the CAD population, during a 64-month median followup, patients with FVIIa-AT levels higher than the median value at baseline (≥ 79 pmol L -1 ) had a two-fold greater risk of both total and cardiovascular mortality. Results were confirmed after adjustment for sex, age, the other predictors of mortality (hazard ratio for total mortality: 2.05 with 95% CI 1.22-3.45, hazard ratio for cardiovascular mortality 1.94 with 95% CI 1.01-3.73, with a slight improvement of C-statistic over traditional risk factors), FVIIa levels, drug therapy at discharge, and even patients using all the usual medications for CAD treatment. High FVIIa-AT levels also correlated with increased thrombin generation. Conclusions: This preliminary study suggests that plasma concentration of FVIIa-AT is a thrombophilic marker of total and cardiovascular mortality risk in patients with clinically stable CAD.

VIIaAT complexes, procoagulant phospholipids, and thrombin generation during postprandial lipemia

“…22 Also, the prothrombotic state, as assessed by the plasma VIIaAT concentration, was associated with the endogenous potential to generate thrombin and a greater risk of mortality in patients with previous stable coronary artery disease. 23 Taken together, many studies suggest VIIaAT as a useful surrogate for TF activity measurement in peripheral blood. 3,[20][21][22][23][24][25][26] Plasma PPL activity increased slightly in response to the oral fat We also studied whether OFTT-induced postprandial lipemia influenced the individual's potential to generate thrombin in vitro.…”

“…23 Taken together, many studies suggest VIIaAT as a useful surrogate for TF activity measurement in peripheral blood. 3,[20][21][22][23][24][25][26] Plasma PPL activity increased slightly in response to the oral fat We also studied whether OFTT-induced postprandial lipemia influenced the individual's potential to generate thrombin in vitro. Weak signs of activation were seen, and the overall responses to the OFTT were not statistically significantly different between cases and controls.…”

Missense changes in the catalytic domain of coagulation factor X account for minimal function preventing a perinatal lethal condition

“…Data were analysed by the statistic software GraphPad Prism 5. Bell‐shaped curves and the specific parameter lag time were obtained by extrapolating the first derivative of relative fluorescence units (RFU) as a function of time (seconds) . Statistical differences were evaluated by the t test.…”

Coagulation Factor XII Levels and Intrinsic Thrombin Generation in Multiple Sclerosis

“…Thrombin generation in plasma samples was evaluated by the addition of a specific thrombin fluorogenic substrate (Calbiochem-Novobiochem, La Jolla, CA, USA) ( 26 , 27 ). Plasma samples were diluted (1/5) in a HBS buffer (Hepes 20 mM, NaCl 150 mM, PEG-8000 0.1%, pH 7.4) and incubated for 5 min at 37°C.…”