STUDIES ON PHOSPHOLIPID ANTIBODIES, APC-RESISTANCE AND ASSOCIATED MUTATION IN THE COAGULATION-FACTOR-V GENE

The influence of antibodies against phospholipids (PLa) on APC respons e was investigated in 155 women with a history of thromboembolism and/ or repeated foetal losses. PLa were determined as antibodies against c ardiolipin (CLa) and phosphatidyl serine (PSa) and as lupus anticoagul ant (LA) tested by dilute Russell's Viper Venom time and by the Textar in/Ecarin ratio. APC-response was studied by a clotting (aPTT-based) a nd by an amidolytic (factor IXa-X-based) assay. A reduced response to APC (APC-resistance) was found in 49% of 65 PLa-positive and in 13% of 90 PLa negative samples ((2)(chi)=23.9; p<0.5x10(-4)). It was more co mmon in the samples with LA, as compared to CLa+PSa positive (58% vs. 30%, not significant). The presence of the mutation causing Arg(506)-G ln substitution in coagulation factor V was investigated in 84 samples . The occurrence of the mutation in APC-resistant patients with CLa+PS a or with LA in one of the two assays was similar to those without PLa (84% and 100%, respectively). In the absence of APC resistance, the o ccurence of the mutation was similar in the samples with and without P La (14% vs. 11%). Samples with LA, determined by both tests used, comp rised a special group where the frequency of the mutation in the APC r esistant samples was significantly reduced (p<0.01). In the latter sam ples, the pathogenic mechanism of APC resistance may be connected with the influence on phospholipid membranes.