0000000000587952
AUTHOR
Rene Van Oerle
Thrombin generation in cardiovascular disease and mortality – results from the Gutenberg Health Study
Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted…
Plasma Kallikrein Contributes to Coagulation in the Absence of Factor XI by Activating Factor IX
Objectives: FXIa (factor XIa) induces clot formation, and human congenital FXI deficiency protects against venous thromboembolism and stroke. In contrast, the role of FXI in hemostasis is rather small, especially compared with FIX deficiency. Little is known about the cause of the difference in phenotypes associated with FIX deficiency and FXI deficiency. We speculated that activation of FIX via the intrinsic coagulation is not solely dependent on FXI(a; activated FXI) and aimed at identifying an FXI-independent FIX activation pathway. Approach and Results: We observed that ellagic acid and long-chain polyphosphates activated the coagulation system in FXI-deficient plasma, as could be demo…
Lipid-Mediated Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample
Abstract Background: Tissue factor pathway inhibitor (TFPI), a Kunitz-type serine protease, is a potent anticoagulant protein in the extrinsic coagulation pathway and acts by inhibiting both the FXa and the Tissue Factor-FVIIa complex. In contrast to total and free TFPI antigen levels, the reference values and clinical determinants of total TFPI activity have not yet been studied in detail in the general population. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and investigate its association with cardiovascular disease (CVD) and total mortality, in a population at large. Methods: For this study, the first 4779 subjects of the population-ba…
Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample.
Abstract Objective Tissue factor pathway inhibitor (TFPI) is a potent anticoagulant protein in the extrinsic coagulation pathway. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and its association with cardiovascular disease (CVD) and total mortality. Methods Total TFPI activity was assessed in a selection of the population-based Gutenberg Health Study (n = 5,000). Statistical analysis was performed to identify the determinants for total TFPI activity as well as the associations with CVD and mortality. Results Multivariable linear regression analysis identified smoking (β 0.095 [0.054–0.136]) as a positive determinant for total TFPI activity…
Abstract 147: The Role of Thrombin Generation in Cardiovascular Disease and Mortality - Results from the Population-based Gutenberg Health Study
Background: Thrombin formation is one of the key enzymatic processes that direct the activity of the hemostatic system. Thrombin generation (TG), a method addressing the overall potential of a given plasma sample to form thrombin, may be a potential tool to improve risk stratification for cardiovascular diseases (CVD). This study aims to explore the relation between TG and cardiovascular risk factors (CVRFs), CVD, and total mortality. Methods: For this study, N=5000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. TG was measured by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor (TF) trigger in platelet poor …
Clinical Determinants of Thrombin Generation Measured in Presence and Absence of Platelets-Results from the Gutenberg Health Study.
AbstractThe tendency of a plasma sample to generate thrombin, a central enzyme in blood coagulation, might be an important indicator of prothrombotic risk linked to cardiovascular disease (CVD), but the presence of platelets may be a critical determinant. Clinical data, laboratory markers and thrombin generation (TG), investigated in both platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1 pM TF, were available in 407 individuals from the Gutenberg Health Study. Given the well-known effect of anticoagulants on TG, subjects taking anticoagulants (n = 15) have been excluded resulting in 392 subjects for further analysis. Lag time, endogenous thrombin potential (ETP) and peak height…