Apixaban does not interfere with protein s or activated protein c resistance (factor v leiden) testing using aptt-based methods

Abstract

Context.-Apixaban causes a false increase in activated protein C resistance (APCR) ratios and possibly protein S activity. Objective.-To investigate whether this increase can mask a diagnosis of factor V Leiden (FVL) or protein S deficiency in an actual population of patients undergoing apixaban treatment and hypercoagulation testing. Design.-During a 4.5-year period involving 58 patients, we compared the following 4 groups: heterozygous for FVL (FVL-HET)/taking apixaban, wild-type/taking apixaban, heterozygous for FVL/no apixaban, and normal APCR/no apixaban. Patients taking apixaban were also tested for protein S functional activity and free antigen (n ¼ 40). Results.-FVL-HET patients taking apixaban had lower APCR ratios than wild-type patients (P,.001). Activated protein C resistance in FVL-HET patients taking apixaban fell more than 3 SD below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite apixaban. In contrast to rivaroxaban, apixaban did not interfere with the assessment of protein S activity (mean activity 93.9 IU/dL, free antigen 93.1 IU/ dL, P ¼.39). A total of 3 of 40 patients (8%) had low free protein S antigen (30, 55, and 57 IU/dL), with correspondingly similar activity results (27, 59, and 52 IU/dL, respectively). Apixaban did not cause a missed diagnosis of protein S deficiency. Conclusions.-Despite apixaban treatment, APCR testing can distinguish FVL-HET from healthy patients, rendering indiscriminate FVL DNA testing of all patients on apixaban unnecessary. Apixaban did not affect protein S activity.