Screening for the FV: Q506 Mutation – Evaluation of Thirteen Plasma-based Methods for their Diagnostic Efficacy in Comparison with DNA Analysis

Abstract

SummaryThe factor V (FV) mutation Q506 that causes resistance to activated protein C (APC) is the genetic defect associated most frequently with venous thrombosis. The laboratory diagnosis can be made by DNA analysis or by clotting tests that measure the degree of prolongation of plasma clotting time upon addition of APC. Home-made and commercial methods are available but no comparative evaluation of their diagnostic efficacy has so far been reported. Eighty frozen coded plasma samples from carriers and non-carriers of the FV: Q506 mutation, diagnosed by DNA analysis, were sent to 8 experienced laboratories that were asked to analyze these samples in blind with their own APC resistance tests. The APTT methods were highly variable in their capacity to discriminate between carriers and non-carriers but this capacity increased dramatically when samples were diluted with FV-deficient plasma before analysis, bringing the sensitivity and specificity of these tests to 100%. The best discrimination was obtained with methods in which fibrin formation is triggered by the addition of activated factor X or Russell viper venom. In conclusion, this study provides evidence that some coagulation tests are able to distinguish carriers of the FV: Q506 mutation from non-carriers as well as the DNA test. They are inexpensive and easy to perform. Their use in large-scale clinical trials should be of help to determine the medical and economic benefits of screening healthy individuals for the mutation before they are exposed to such risk factors for venous thrombosis as surgery, pregnancy and oral contraceptives.