Evaluation of a new chronometric assay for factor V Leiden-dependent APC resistance

Since the first description by Dahlback et al (1) of a hereditary defect in the plasma of three unrelated thrombophilic patients characterized by a poor anticoagulant response to activated protein C (APC), many reports have shown a high prevalence of the APC resistance in both the general and thrombophilic populations (2-6). In almost all cases APC resistance is due to a single point mutation in the factor V gene, (a G to A substitution at nucleotide position 1691), which predicts the synthesis of a factor V molecule (FVQ506 or FV Leiden) in which the Arg 506 in one of the APC cleavage sites is replaced by Gln (7), rendering factor Va resistant to inactivation by APC. The FVQ506 mutation is the most frequent hereditary risk factor for venous thrombosis (2, 5, 6, 8-10) making an assay for APC resistance with a high predictive value for the muation highly desirable, especially when molecular diagnosis at the gene level is not possible. The aim of this study was to evaluate the performance of a new factor Xa-based assay for the FV Leiden-dependent APC resistance.