Influence of coagulation factors and tissue factor concentration on the thrombin generation test in plasma

Duchemin, Jérôme; Pan‐Petesch, Brigitte; Arnaud, Bertrand; Blouch, Marie-Thérèse; Abgrall, Jean-François

doi:10.1160/th07-09-0581

Cited by 102 publications

(34 citation statements)

References 30 publications

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“…ETP value represents total endogenous thrombin amount that can be generated by TF stimulation. The ETP value increases as procoagulant factors increase or anticoagulant factors decrease [ 17 , 19 ]; therefore, our results showed that high levels of ETP were observed in hyperlipidemia, suggesting relatively high levels of procoagulant factors. Peak thrombin level is also changed similar to ETP values.…”

Section: Discussionmentioning

confidence: 81%

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Influence of Blood Lipids on Global Coagulation Test Results

Kim

Song

et al. 2015

Ann Lab Med

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BackgroundHigh levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA).MethodsPT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II).ResultsThe procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values.ConclusionHigh blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

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Section: Discussionmentioning

confidence: 81%

“…TGA's lag time is mainly determined by factor VII, factor XII, and protein S levels [ 17 , 19 ]. In other words, a decrease in factor VII and XII or elevation of protein S can increase lag time.…”

Section: Discussionmentioning

confidence: 99%

Influence of Blood Lipids on Global Coagulation Test Results

Kim

Song

et al. 2015

Ann Lab Med

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“…Either way, activation of the endothelium results in an increase of PAI-1 and vWF. The increase in PAI-1 may explain the decrease in PAPc [51], while the increase in ETP might be explained by the increased levels of factor VIII [3,52] commonly associated with an increase in vWF and other pro-coagulants [53]. Both impaired IFN production and endothelial activation may play a role in the increased systemic haemostatic activity found in patients with mild asthma.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects: an observational study

Majoor¹,

Pol²,

Kamphuisen³

et al. 2014

Respir Res

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BackgroundAsthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance.Methods28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation).Results13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01).Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1.ConclusionsExperimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load.Trial registrationThis trial was registered at the Dutch trial registry (http://www.trialregister.nl): NTR1677.

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“…a normal assay readout. Sensitivity of different global coagulation tests for deficiencies in procoagulant factors are based on data provided in the following publications: clotting time based PT and APTT [38,39], thrombin generation assay (TGA) [40], thromboelastography (TEG) [41]. The presence of factor V in the assay reagents makes the Owren PT insensitive to this coagulation factor.…”

Section: Introductionmentioning

confidence: 99%

Global assays and the management of oral anticoagulation

Brinkman

2015

Thrombosis J

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Coagulation tests range from global or overall tests to assays specific to individual clotting factors and their inhibitors. Whether a particular test is influenced by an oral anticoagulant depends on the principle of the test and the type of oral anticoagulant. Knowledge on coagulation tests applicable in monitoring status and reversal of oral anticoagulation is a prerequisite when studying potential reversal agents or when managing anticoagulation in a clinical setting. Specialty tests based on the measurement of residual activated factor X (Xa) or thrombin activity, e.g., are highly effective for determining the concentration of the new generation direct factor Xa- and thrombin inhibitors, but these tests are unsuitable for the assessment of anticoagulation reversal by non-specific prohemostatic agents like prothrombin complex concentrate (PCC) and recombinant factor VIIa (FVIIa). Global coagulation assays, in this respect, seem more appropriate. This review evaluates the current status on the applicability of the global coagulation assays PT, APTT, thrombin generation and thromboelastography in the management of oral anticoagulation by vitamin K antagonists and the direct factor Xa and thrombin inhibitors. Although all global tests are influenced by both types of anticoagulants, not all tests are useful for monitoring anticoagulation and reversal thereof. Many (pre)analytical conditions are of influence on the assay readout, including the oral anticoagulant itself, the concentration of assay reagents and the presence of other elements like platelets and blood cells. Assay standardization, therefore, remains an issue of importance.

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Influence of coagulation factors and tissue factor concentration on the thrombin generation test in plasma

Cited by 102 publications

References 30 publications

Influence of Blood Lipids on Global Coagulation Test Results

Influence of Blood Lipids on Global Coagulation Test Results

Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects: an observational study

Global assays and the management of oral anticoagulation

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