Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome

Abstract

Rivaroxaban can affect lupus anticoagulant (LA) testing and antiphospholipid antibodies (aPL) may interfere with the anticoagulant action of rivaroxaban. To establish the influence of rivaroxaban on LA detection and of aPL on the anticoagulant action of rivaroxaban. Rivaroxaban and 52 IgG preparations (20 LA+ve, 12 LA-ve thrombotic antiphospholipid syndrome [APS] patients, and 20 normal controls [NC]) were spiked into pooled normal plasma (PNP) for relevant studies. LA detection was also studied in APS patients receiving rivaroxaban 20mg once daily. In vitro spiking of samples with rivaroxaban showed no false positive LA with Textarin time, Taipan venom time/Ecarin clotting time (TVT/ECT), dilute prothrombin time (dPT) and in-house dilute Russell's viper venom time (DRVVT), but false positives in the majority of NC and LA negative IgG with two commercial DRVVT reagents at 250ng/mL but not 50ng/mL rivaroxaban. Ex vivo studies: six LA+ve patients on rivaroxaban remained LA positive with TVT/ECT and DRVVT at peak (162-278ng/mL) and trough (30-85ng/mL) rivaroxaban levels. Six LA-ve patients became (apparently) LA+ve with two DRVVT reagents (test/confirm ratio median [confidence interval], 1.6 [1.3-1.8], 1.6 [1.4-1.9]) but not with TVT/ECT at peak rivaroxaban levels, and remained LA-ve with both DRVVT reagents and TVT/ECT at trough levels. aPL positive IgG spiking of PNP had no effect on rivaroxaban's anticoagulant action on thrombin generation or rivaroxaban anti-Xa levels. The TVT/ECT ratio and Textarin time were not affected even at peak rivaroxaban levels, enabling detection of LA exvivo. aPL had no effects on rivaroxaban's anticoagulant action invitro.