Prothrombin conversion accelerates with increasing age in women but not in men: findings from the Moli-sani Cohort Study

Background: The thrombin dynamics method has been used as an add-on analysis method for the thrombin generation test over the past years to study the balance between pro- and anticoagulant pathways. Thrombin generation test results are known to be age-dependent and gender-dependent. Objectives: In this study, we investigated the association of thrombin dynamics parameters with age and gender. Methods: Thrombin generation was measured in 17,530 individuals of the Moli-sani cohort using the Calibrated Automated Thrombinography method. Thrombin dynamics analysis was performed to quantify parameters of prothrombin conversion and thrombin inactivation. Differences in thrombin dynamics parameters in men and women and in different age groups were investigated. Additionally, reference ranges for each age and gender category were established. Results: Thrombin dynamics parameters change throughout life, and these changes differ between men and women. The total amount of prothrombin conversion decreased with increasing age (-14.4% difference between 35-44 and 85+ years of age; R = -0.234; P < .001), although the maximum rate of prothrombin conversion increased with age in women (+18.2%; R = 0.079; P < .001). The ability to inactivate thrombin decreases with age as well (-13.7%; R = -0.320; P < .001), indicating a shift towards a more procoagulant phenotype with advancing age. This is reinforced by the diminished inhibitory actions of thrombomodulin on the procoagulant pathway. Conclusion: The balance between prothrombin conversion and thrombin inactivation becomes more procoagulant with increasing age, but only in women. Therefore, age and gender appropriate reference values for thrombin dynamics parameters would be of interest for the clinical implementation of thrombin generation and thrombin dynamics analysis.