Molecular abnormalities responsible for thrombosis. Genetic aspects

The association between congenital deficiencies and recurrent thrombosis strongly suggests that antithrombin III, protein C and protein S play a major role in inhibiting thrombin formation in vivo. Genetic analysis using DNA fragment amplification by polymerase chain reaction and direct gene sequencing has led to the identification of many novel mutations in qualitative and quantitative deficiencies. Elucidation of the molecular basis of these deficiencies is critical to our understanding of natural antithrombotic mechanisms. It not only provides information on the structural features governing protein function, but also permits a better classification, based on genomic abnormalities of hereditary deficiencies responsible for mild to severe phenotypes and may prove of further value to define the most pertinent plasma assays for routine diagnosis.