The plasma hemostatic proteome: thrombin generation in healthy individuals

Background and objectives: The range of plasma concentrations of hemostatic analytes in the population is wide, In this study these components of blood coagulation phenotype are integrated in an attempt to predict clinical risk. Methods: We modeled tissue factor (TF)-induced thrombin generation in the control population (N = 473) from the Leiden Thrombophilia Study utilizing a numerical simulation model. Hypothetical thrombin generation Curves were established by modeling pro- and anticoagulant factor levels for each individual. These curves were evaluated using parameters which describe the initiation, propagation and termination phases of thrombin generation, i.e. time to 10 nm thrombin (approximate clot time), total thrombin and the maximum rates and levels of thrombin generated. Results and conclusions: The time to 10 nm thrombin varied over a 3-fold range (2.9-9.5 min), maximum levels varied over a similar to 4-fold range (200-800 rim), maximum rates varied similar to 4.8-fold (90-435 nM min(-1)) and total thrombin varied similar to 4.5-fold (39-177 mu M s(-1)) within this control population. Thrombin generation curves, defined by the clotting factor concentrations, were distinguished by sex, age, body mass index (BMI) and oral contraceptive (OC) use. Our results show that the capacity for thrombin generation in response to a TF challenge may represent a method to identify an individual's propensity for developing thrombosis.