[Factors influencing thrombin generation measured as thrombin-antithrombin complexes levels and using calibrated automated thrombogram in patients with advanced coronary artery disease].

INTRODUCTION Haemostatic factors play an important role in atherothrombosis. Thrombin generation is a crucial stage of blood coagulation. OBJECTIVES Comparison of different thrombin generation markers: thrombin-antithrombin complex (TAT) generation and calibrated automated thrombogram method (CAT). Identification of factors influencing thrombin generation in patients with stable angina (SA) enrolled to the coronary artery bypass grafting (CABG) surgery. Analysis of traditional (age, gender, hypertension and diabetes) and novel (fibrinogen and C-reactive protein [CRP]) risk factors and the antiplatelet therapy (aspirin 75-150 mg/d) in relation to coagulation. PATIENTS AND METHODS In 135 SA patients with left main coronary artery stenosis (> 50%) or major epicardial artery stenosis (> 70%), plasma TAT levels, maximal thrombin concentration (C(max)) and endogenous thrombin potential (ETP) were determined. A marker of the platelet activation (beta-thromboglobulin) was also measured. RESULTS No correlations among TAT, C(max), ETP, risk factors and beta-thromboglobulin were observed. Linear regression model showed that independent predictors of TAT levels were age (beta = 0.5; p = < 0.0001), male gender and diabetes (beta = 0.36; p = 0.02). CRP independently predicted TAT and ETP (beta = -0.24 and beta = 0.22; p < 0.05, respectively), while fibrinogen predicted C(max) (beta = 0.21; p < 0.05). Independent predictors of beta-thromboglobulin were a male gender and aspirin use cessation (beta = 0.46; p = 0.01). Aspirin treatment had no effect on thrombin generation. CONCLUSIONS Age, higher fibrinogen, CRP, diabetes and male gender influence thrombin generation and/or coagulation activation in SA patients. Plasma levels of thrombin-antithrombin complexes do not correlate with the parameters obtained using the calibrated automated thrombogram method (C(max), ETP).

[1]  G. Niccoli,et al.  Instability mechanisms in unstable angina according to baseline serum levels of C-reactive protein: the role of thrombosis, fibrinolysis and atherosclerotic burden. , 2007, International journal of cardiology.

[2]  E. Stępień,et al.  Altered fibrin clot structure in patients with advanced coronary artery disease: a role of C‐reactive protein, lipoprotein(a) and homocysteine , 2007, Journal of thrombosis and haemostasis : JTH.

[3]  S Butenas,et al.  Caution in the interpretation of continuous thrombin generation assays , 2007, Journal of thrombosis and haemostasis : JTH.

[4]  K. Mann,et al.  Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions. , 2007, Blood.

[5]  A. Gori,et al.  Markers of hypercoagulability and inflammation predict mortality in patients with heart failure , 2006, Journal of thrombosis and haemostasis : JTH.

[6]  J. Brittenden,et al.  Markers of coagulation activation, endothelial stimulation and inflammation in patients with peripheral arterial disease. , 2005, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[7]  J. Paramo,et al.  Prothrombin Fragment 1+2 Is Associated With Carotid Intima-Media Thickness in Subjects Free of Clinical Cardiovascular Disease , 2004, Stroke.

[8]  G. Davı̀,et al.  Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women. , 2003, The Journal of clinical endocrinology and metabolism.

[9]  F. Rosendaal,et al.  Estrogens, progestogens and thrombosis , 2003, Journal of thrombosis and haemostasis : JTH.

[10]  J. Aznar,et al.  Inflammation, fibrinogen and thrombin generation in patients with previous myocardial infarction. , 2002, Haematologica.

[11]  E. Bramucci,et al.  Thrombogenic potential of human coronary atherosclerotic plaques. , 2001, Blood.

[12]  K. Mann,et al.  Simvastatin Depresses Blood Clotting by Inhibiting Activation of Prothrombin, Factor V, and Factor XIII and by Enhancing Factor Va Inactivation , 2001, Circulation.

[13]  S. Olson,et al.  Heparin Enhances the Specificity of Antithrombin for Thrombin and Factor Xa Independent of the Reactive Center Loop Sequence , 2001, The Journal of Biological Chemistry.

[14]  T. Wascher,et al.  Alterations in platelet Ca2+ signalling in diabetic patients is due to increased formation of superoxide anions and reduced nitric oxide production , 1999, Diabetologia.

[15]  J. Morser,et al.  Both Cellular and Soluble Forms of Thrombomodulin Inhibit Fibrinolysis by Potentiating the Activation of Thrombin-activable Fibrinolysis Inhibitor* , 1998, The Journal of Biological Chemistry.

[16]  L. Mazzanti,et al.  Decreased nitric oxide synthase activity in platelets from IDDM and NIDDM patients , 1998, Diabetologia.

[17]  A. Folsom,et al.  Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. , 1997, Circulation.

[18]  Samin K. Sharma,et al.  Identification of active tissue factor in human coronary atheroma. , 1996, Circulation.

[19]  K. Ishikawa,et al.  Platelet-dependent thrombin generation in patients with diabetes mellitus: effects of glycemic control on coagulability in diabetes. , 1996, Journal of the American College of Cardiology.

[20]  K. Oku,et al.  Clinical Significance of New Coagulation and Fibrinolytic Markers in Ischemic Stroke Patients , 1991, Stroke.

[21]  J. T. ten Cate,et al.  Laboratory and clinical evaluation of an assay of thrombin-antithrombin III complexes in plasma. , 1988, Clinical chemistry.

[22]  A. P. Ball,et al.  Generation of the combined prothrombin activation peptide (F1-2) during the clotting of blood and plasma. , 1977, The Journal of clinical investigation.