CONGENITAL RESISTANCE TO ACTIVATED PROTEIN-C IN PATIENTS WITH LUPUS ANTICOAGULANTS - EVALUATION OF 2 FUNCTIONAL ASSAYS

The R506Q mutation (''Factor V Leiden'') is responsible for the resist ance to activated Protein C (aPCR), that is evaluated by coagulation t ests. Such tests cannot be used in patients with lupus anticoagulants (LAs), due to the interfering effect exerted by these antibodies on '' in vitro'' phospholipid-dependent coagulation tests. For this reason, assays have been developed to evaluate aPCR that are insensitive to th e presence of LA antibodies. We evaluated two such coagulation tests i n the plasma of 82 consecutive patients with LAs. By polymerase chain reaction 3 patients (3.6%) were found heterozygous for the R506Q mutat ion. aPCR was evaluated by two clotting assays, proposed to be ''insen sitive'' to the presence of LAs: 1. aPCR-tissue factor-based assay, us ing Factor V deficient plasma and 1:40 diluted test plasma; 2. aPCR-dR VVT-based assay with highly concentrated phospholipids. Their interass ay coefficient of variation was 28% and 6.2%, respectively. Compared t o the polymerase chain reaction analysis, the 2 tests displayed the fo llowing characteristics: sensitivity 67% vs 100%, specificity 92% vs 9 6%, positive predictive value 25% vs 50%, negative predictive value 99 % vs 100%, respectively. Among LA patients without the R506Q mutation, 5 scored positive in the aPCR-tissue factor-based assay, 2 in the aPC R-dRWT-based assay and another one in both assays. Our findings sugges t that the aPCR-dRVVT-based test is more reliable and sensitive than t he aPCR-tissue factor-based one to the R506Q mutation in patients with LAs. Both assays, when negative, make unlikely the presence of the R5 06Q mutation. Polymerase chain reaction analysis remains, however, to be performed when either test is positive.