MODIFIED APC-RESISTANCE TEST - VARIABLE RATIOS WITH RESPECT TO SOURCEOF FACTOR V-DEFICIENT PLASMA

A single point mutation of the factor V (FV) gene, leading to the subs titution Arg506Gln in the FV molecule (FV-Leiden) and hence resistance to its breakdown by activated protein C (APC), is the most prevalent risk factor for venous thrombosis in the Caucasians, A ratio determine d by activated partial thromboplastin time (APTT) of test plasma in th e presence or absence of exogenous APC (the APC ratio), is the method widely used to screen individuals with this risk factor for thrombosis , Because of functional defects of vitamin K-dependent clotting factor s in patients on oral anticoagulant therapy, this method cannot be app lied to those patients without modification. One modification is to mi x test plasma (1:5 or 1:10) with FV-deficient plasma so that 80-90% of functioning vitamin K-dependent factors are supplied by the FV-defici ent plasma, Even with 10-20% of FV in the mixture, APC-resistance stil l can be demonstrated, In this report, we present our results of the m odified APC-sensitivity assay using FV-deficient plasma from different commercial sources, APC ratios determined by the original method in w hich test plasma is not mixed with FV-deficient plasma can be signific antly different from those determined by the modified method in which test plasma is diluted 1:5 with FV-deficient plasma. This difference b etween methods was observed not only in normal individuals, but also i n FV-Leiden positive individuals, and in patients on warfarin therapy, Further, APC ratios varied significantly depending on the commercial source of the FV-deficient plasma. The modified method is apparently s uitable to identify APC-resistance in patients on warfarin therapy, as well as in individuals not receiving anticoagulant treatment, However , one must be aware that APC-resistance ratios obtained with the modif ied method are likely to be different from those established with the original method, and the source of FV-deficient plasma can be a factor influencing the ratios in the former cases. (C) Wiley-Liss, Inc.