Empirical and theoretical phenotypic discrimination.

We have developed an integrated approach that combines empirical and computational methodologies to define an individual's thrombin phenotype. We have evaluated the process of thrombin generation in healthy individuals and individuals with defined pathologies in order to develop general criteria relevant to assess an individual's propensity for hemorrhage or thrombosis. Three complementary hypotheses have emerged from our work: (i) compensation by the ensemble of other coagulation proteins in individuals with specific factor deficiencies can 'normalize' an individual's thrombin generation process and represents a rationale for their unexpected phenotype; (ii) individuals with clinically unremarkable factor levels may present thrombin generation profiles typical of individuals with hemostatic complications; and (iii) in some hemostatic disorders a specific pattern of expression of a small ensemble of coagulation factors may be sufficient to explain the overall phenotype.