Lupus Anticoagulant Interference in Activated Protein C Resistance Testing

Abstract

Second-generation activated protein C resistance (APC-R) assay was developed to avert interferences from lupus anticoagulant (LA) and warfarin therapy by prediluting the patient sample with factor V (FV)-depleted plasma. We investigated the effect of LA on the second generation APC-R assay in 121 LA-positive patients. Twenty-five APC-R-positive patients were tested for the mutation in FV (Leiden, Hong Kong, and Cambridge). Eleven had FV Leiden and twelve were negative for any mutation (2 were not tested). Of 12, 8 had APC-R suggestive of heterozygous and 4 had APC-R suggestive of homozygous defects. These patients had strong LA activity, compared to those with concurrent FVL. This was associated with a trend toward increased thrombosis risk compared to those with normal APC-R. These findings suggest that LA causes acquired APC-R, reflecting an in vivo pathophysiologic effect of LA rather than merely an in vitro phenomenon even with the second generation APC-R assay.