A message from Crystal Azevedo, Eastern Maine Healthcare System: Hello George, I was wondering if you or your colleagues are familiar with the interfering effects of rivaroxaban on tests for thrombophilia? I am testing a sample of plasma where the prescribed dose is 15 mg twice per day, and most of the test results are suspect. Thanks as always for your input!
Hi, Crystal, and thank you for your question. At the International Society on Thrombosis and Haemostasis biennial meeting last week, Dr. Trevor Baglin of Cambridge University Hospitals in the UK indicated that rivaroxaban (Xarelto®), apixaban(Eliquis®), and, by generalization, yet-to-be released edoxaban, all direct Xa inhibitors, prolong the prothrombin time (PT) and partial thromboplastin time (PTT) in an unpredictable fashion, though they do not affect the thrombin time or the clot-based (Clauss) fibrinogen assay, as does dabigatran (Pradaxa®). So, any PT– or PTT-based assay, such as lupus anticoagulant testing, the functional protein S or the clot-based protein C or antithrombin assay, is unreliable. I’ve not seen data on chromogenic assays, though I presume they will function normally.
Added July 28: Also, I just reviewed a poster on the subject from the ISTH meeting:Fareed J, Syed D, Kahn D, Jeske W, Escalante V, Iqbal O, Hoppensteadt D, Cunanan J, Walenga JM. Biochemical and pharmacological differentiation of dabigatran, apixaban and rivaroxaban. J Thromb Haemostas 2013;11 Suppl 2: Abstr PB 2.47-1. Dr. Fareed’s group did an in vitro study and demonstrated that the anti-Xa anticoagulants rivaroxaban and apixiban prolonged the activated clotting time, PT, PTT, thromboelastograph (TEG), and thrombin generation test. In all cases, the direct thrombin inhibitor dabigatran had a larger effect on the assay than the anti-Xa drugs, however, any measurement based on the PT and PTT is affected. I presume, but have seen no proof, that rivaroxaban would interfere with the chromogenic antithrombin assay, which employs Xa as its substrate, but perhaps not the chromogenic protein C nor any immunoassay or molecular assay.
some additional data:
The results from antithrombin assay
some additional data:
The results from antithrombin assays were dependent on the type of reagent, with the Xa-based assay being sensitive to rivaroxaban with an estimated increase of 0.09 IU mL(-1) per 100 ?g L(-1) rivaroxaban. The APTT-based assay for APC resistance is affected in a dose-dependent manner whereas an assay based on the activation of coagulation at the prothrombinase level was unaffected.
Hillarp A et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost 2011;9:133-9.
Two hours after rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling, protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban.
Mani H, et al. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions. Thromb Haemost 2013;109:127-36.