Thrombin generation profiles in deep venous thrombosis

BackgroundL: Reliable markers and methods to predict risk for thrombosis are essential to clinical management. Objective: Using an integrated approach that defines an individual's comprehensive coagulation phenotype might prove valuables in identifying individuals at risk for experiencing a thrombotic event. Methods: Using a numerical simulation model, we generated tissue factor (TF) initiated thrombin curves using coagulation factor levels from the Leiden Thrombophilia Study population and evaluated thrombotic risk, by sex, age, smoking, alcohol consumption, body mass index (BMI) and oral contraceptive (OC) use. We quantitated the initiation, propagation and termination phases of each individuals comprehensive TF-initiated thrombin generation curve by the parameters: time to 10 nM of thrombin, maximum time, level and rate (MaxR) of thrombin generated and total thrombin. Results: The greatest risk association was obtained Using MaxR; with a 2.6-fold increased risk at MaxR exceeding the 90th percentile. The odds ratio (OR) for MaxR was 3.9 in men, 2.1 in women, and 2.9 in women on OCs. The association of risk with thrombin generation did not differ by age (OR:2.8 <= 45 years > OR:2.5) BMI (OR:2.9 <= 26 kg m(-2) > :2.3) Or alcohol Use. In both numerical simulations and empirical synthetic plasma, OC use created extreme shifts ill thrombin generation in both control women and women with it prior thrombosis, with a larger shirt in thrombin generation ill control women, This suggets in interaction of OC use with underlying prothrombotic abnormalities. Conclusions: Thrombin generation based Upon the individual's blood composition is associated with the risk for thrombosis and may be useful LIS a predictive market- for evaluating thrombosis on an individual basis.