Utility of Thrombin-Generation Assay in the Screening of Factor V G1691A (Leiden) and Prothrombin G20210A Mutations and Protein S Deficiency

BACKGROUND: The thrombin-generation assay has a variety of clinical uses, including diagnosis of thromboembolism-related disease, and particular profiles are associated with thrombophilic risk factors. The aim of this study was to evaluate the use of this assay in screening and identifying patients who require specific thrombophilic testing. METHODS: We used a 2-step approach to perform specific thrombophilic testing and thrombin-generation assays on 169 consecutive patients. The first step was to identify particular profiles of thrombin generation corresponding to each type of thrombophilic risk factor and to determine the pertinent variables related to thrombin generation. We then performed ROC curve analysis for each predefined variable to determine the relevant cutoffs for identification of patients in need of further testing (negative predictive value, 100%). RESULTS: Suggestive profiles were seen in factor V Leiden (n = 49) and prothrombin (n = 12) mutations and in protein S deficiency (n = 12). ROC curves showed that factor V Leiden may be excluded when the difference between lag times obtained in the absence and presence of activated protein C (APC) is >1.5 min and that prothrombin G20210A may also be excluded when the peak thrombin concentration is 63%. CONCLUSION: The thrombin-generation assay represents a promising tool for screening thrombophilic risk factors, particularly in patients who are carriers of factor V Leiden or prothrombin G20210A mutations and patients with protein S deficiency.