Evaluation of Thrombin Generation in Patients with Stable Coronary Artery Disease with a Prior Myocardial Infarction

Background. Despite invasive technologies and the advancement of modern pharmacotherapy in the treatment of coronary artery disease (CAD), patients still have risks of complications. There is a special group of patients with CAD with a prior myocardial infarction (MI). As demonstrated, a prior MI increases risk of recurring cardiovascular events. Thus, there was a decrease in the frequency of such events to a greater extent than that with aspirin monotherapy in the clinical study on combined antiplatelet and anticoagulant therapy in this group. By contrast, there was an increase in the frequency of large bleeding, which is a significant limitation of the combined therapy. Therefore, it is relevant to identify subjects with CAD and high thrombotic risk for individualization of therapy. In this study, the activity of thrombin formation was assessed with help of an integral hemostasis assessment method — a thrombin generation test (TGT) in patients with CAD regarding the presence or absence of MI in anamnesis.

Objective. Investigation of the thrombogenic activity with the help of TGT in patients with CAD with a prior MI.

Materials and methods. A total of 59 patients with a diagnosis of stable CAD hospitalized for myocardial revascularization were examined. Of these, 28 patients who had a history of MI (group 1), and 31 patients without previous MI (group 2). The control group consisted of 31 people without clinical manifestations of atherosclerosis. In vitro thrombin generation in platelet-poor plasma was measured by means of the calibrated automated thrombogram method (Thrombinoscope BV, Maastricht, the Netherlands). Four parameters were derived from the thrombin generation curves: LT (lag time — initiation phase of coagulation, min), Peakthr (peak thrombin concentration, nmol), ttPeak (time to peak concentration, min), ETP (endogenous thrombin potential — area under the thrombin generation curve), and VI (velocity index of thrombin generation, nmol/min).

Results. A significant increase in TGT parameters was revealed in Group 1 compared to Group 2 and control group: the peak height of thrombin (304.09 [279.97-353.91] nmol vs 283.38 [209.07-313, 54] and 258.86 [211.28-299.50] nmol, respectively (p < 0.01)) and the VI thrombin (131.78 [111.98-158.38] nmol/min vs 100.64 [56.33-122.19] and 77.96 [62.45-122,54,] nmol/min, respectively, (p < 0.001)). There was a significant positive correlation between ETP and total cholesterol level (r = 0.35, p = 0.01), LDL (r = 0.32, p = 0.02) in the general group of patients with CAD.

Conclusion. In patients with CAD and prior MI, a higher quantity and rate of thrombin formation were found by TGT, determining the test perspectivity for assessment of thrombotic risk in order to isolate subjects with an indication for more strong antithrombotic therapy.

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