Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome

J Thromb Haemost. 2015 Jul;13(7):1264-73. doi: 10.1111/jth.12917. Epub 2015 May 9.

Abstract

Introduction: Rivaroxaban can affect lupus anticoagulant (LA) testing and antiphospholipid antibodies (aPL) may interfere with the anticoagulant action of rivaroxaban.

Aims: To establish the influence of rivaroxaban on LA detection and of aPL on the anticoagulant action of rivaroxaban.

Methods: 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 20 mg once daily.

Results: 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 250 ng/mL but not 50 ng/mL rivaroxaban. Ex vivo studies: six LA+ve patients on rivaroxaban remained LA positive with TVT/ECT and DRVVT at peak (162-278 ng/mL) and trough (30-85 ng/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.

Conclusions: The TVT/ECT ratio and Textarin time were not affected even at peak rivaroxaban levels, enabling detection of LA ex vivo. aPL had no effects on rivaroxaban's anticoagulant action in vitro.

Keywords: Russell's viper venom time; antiphospholipid syndrome; lupus anticoagulant; prothrombin activator (Taipan venom); rivaroxaban.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antiphospholipid / blood*
  • Antiphospholipid Syndrome / blood
  • Antiphospholipid Syndrome / diagnosis
  • Antiphospholipid Syndrome / drug therapy*
  • Biomarkers / blood
  • Blood Coagulation / drug effects*
  • Blood Coagulation Tests
  • Case-Control Studies
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use*
  • False Positive Reactions
  • Humans
  • Immunoglobulin G / blood*
  • Lupus Coagulation Inhibitor / blood
  • Predictive Value of Tests
  • Reproducibility of Results
  • Rivaroxaban / adverse effects
  • Rivaroxaban / therapeutic use*
  • Thrombosis / blood
  • Thrombosis / diagnosis
  • Thrombosis / drug therapy*
  • Treatment Outcome

Substances

  • Antibodies, Antiphospholipid
  • Biomarkers
  • Factor Xa Inhibitors
  • Immunoglobulin G
  • Lupus Coagulation Inhibitor
  • Rivaroxaban