Biochemical determinants of thrombin generation in a general population with arterial and venous disease background

Background: The current study aims to identify the biochemical determinants of plasma thrombin generation in a large population-based study by comparing individuals with a history of arterial or venous thrombosis to cardiovascular healthy individuals. Methods: This study comprised 502 individuals with a history of arterial disease, 195 with history of venous thrombosis and 1402 cardiovascular healthy individuals (reference sample) from the population-based Gutenberg Health Study (GHS). Calibrated Automated Thrombography was assessed and coagulation factors were measured by means of BCS XP Systems. To assess the biochemical determinants of TG variables, a multiple linear regression analysis, adjusted for age, sex and antithrombotic therapy, was conducted. Results: The lag time was mainly positively associated with the natural coagulant and anti-coagulant factors in the reference sample, i.e. higher factors result in a longer lag time. The same determinants were negative for individuals with a history of arterial or venous thrombosis, with a 10 times higher effect size. ETP was predominantly positively determined by factor II, VIII, X and IX in all subsamples. However, the effect sizes of the reported associations were 4 times higher for the arterial and venous subsamples in comparison to the reference sample. Conclusion: This large-scale analysis demonstrated a stronger effect of the coagulant and natural anti-coagulant factors on the thrombin potential in individuals with a history of arterial or venous thrombosis as compared to healthy individuals, which implicates sustained alterations in the plasma coagulome in subjects with a history of thrombotic vascular disease, despite intake of antithrombotic therapy.