Rivaroxaban

The following should be considerations for the quantitative measurement of Xarelto^® (rivaroxaban) ^1,2:

• Suspected accumulation of drug (ie, fragile elderly patients with renal insufficiency)
• Overdose
• Acute renal failure
• Severe renal failure and dialysis dependence
• Bleeding complications or thrombosis during treatment
• Emergency situations (if available in time)

                o   Examples: prior to urgent surgery; life-threatening bleeding; stroke                        (if fibrinolytic treatment indicated); acute percutaneous coronary                        intervention (if heparin bolus indicated). It should be noted that                        measuring rivaroxaban levels is not recommended as a method of                        ensuring absence of drug before invasive procedures. Instead,                        thrombin time and anti-Xa activity may be obtained by the local                        laboratory to assess the presence of rivaroxaban or other direct oral                        anticoagulants

• Suspected drug interactions

For patients with a body mass index >40 kg/m², based on pharmacokinetic studies and expert opinion, obtaining a peak and trough value after at least 5 doses may be of interest to ensure that plasma concentrations are approximately within the range published for other patients²

The method is a modified, chromogenic anti-Xa assay. The optical density derived from the patient sample is compared to that of calibrators with known rivaroxaban concentration. The resulting concentration is reported in mg/L. 

No. However, peak and trough levels have been observed based on adult Phase II clinical trial data and simulated virtual data (Table below.). 

Note that the lower limit of detection for this rivaroxaban assay is 30 mg/L. Rivaroxaban trough levels may be below this value. For this reason, it is suggested that samples be collected at the peak (3-4 hours after the last dose).

Although rivaroxaban has been approved in children, given the number of potential formulations and developmental changes in pediatric patients, no established therapeutic reference ranges have been established. However, rivaroxaban does have a predictable, dose-dependent PK/PD profile across age groups of neonates and children.³

Other anti-Xa anticoagulants, including unfractionated heparin, low molecular weight heparin (enoxaparin, tinzaparin, dalteparin), and fondaparinux, may interfere with the results.

Gross lipemia, hemolysis >375 mg/dL, and gross icterus also interfere with the assay.

Yes, rivaroxaban can prolong the prothrombin time/international normalized ratio (PT/INR) and the activated partial thromboplastin time (aPTT) and therefore falsely decrease clotting-based factor assays (factors II, V, VII, VII, IX, XI, and XII) or yield an inhibitor pattern. Clotting-based methods for protein C and S activity may also be falsely elevated. A lupus anticoagulant test may also be impacted, resulting in a false positive. 

This interference is typically concentration dependent. It should be noted that neither antithrombin III activity nor activated protein C resistance testing performed at Quest Diagnostics are affected by rivaroxaban or other anti-Xa medications such as apixaban or edoxaban; fibrinogen activity, thrombin time, and reptilase assays are not affected by this medication.⁴