Determination of Rivaroxaban in Urine Samples From Patients Undergoing Elective Hip- and Knee Replacement Surgery Using a Point of Care Method

Abstract 1162

Rivaroxaban is approved at fixed dose for several indications to prevent thromboembolism. Despite the lack of need to dose adjust rivaroxaban it may be necessary to determine its activity/concentration in specific patient populations. Several assays are available to determine the anticoagulant in plasma samples. A point of care (POC) method may provide immediate results for patients requiring acute medical interventions and facilitate therapeutic decisions.

Plasma and urine samples were taken from patients (n=150) after having given written informed consent before and between days 4 to 6 following primary elective total knee (THR) and hip replacement (THR) surgery on antithrombotic therapy with 10mg rivaroxaban od. For laboratory assays, rivaroxaban was purified from commercially available Xarelto®. The compound was characterized by analytical methods and was quantified in plasma samples using the factor Xa specific S2222 chromogenic substrate assay as described (J Thromb Haemost 2012,10:1433–6). In urine rivaroxaban was determined by a POC method incubating the lyophilized reagents on mini-strips followed by incubation with patient‘s urine (patent No GB1019674.9). The development of colour of urine samples 10 min after incubation with reagents was determined quantitatively by optical density (OD) measurement and judged by eye qualitatively according negative and positive colour (three independent readings by SD, SK, CG, and photographic documentation). To determine the positive and negative predictive value (PPV, NPV) of plasma samples, a cutoff value of <25 ng/ml rivaroxaban was defined. The PPV and NPV of the POC method with urine samples were determined according to positive and negative results of colour development judged by eye reading.

Before administration of rivaroxaban 127/144 patients displayed plasma concentrations of 11.1+7.1 ng/ml (mean, standard deviation) and 17 patients a concentrations of 40.4+13.1 ng/ml (cut off value >25ng/ml). The NPV was 88.2%. During therapy the concentration of rivaroxaban was 76.7+36.6 ng/ml in 113/135 patients (above cutoff value) and 14.3+5.2 ng/ml in 22/135 patients (below cutoff value). The PPV was 83.7%. Values were negative in 16.3% of these patients. Using the POC method for rivaroxaban in urine all of 117 patients had negative values with OD measurement (1.23+0.14 OD units) and eye measurement. The NPV was 100%. During therapy with rivaroxaban 4/125 patients had negative colour development by eye measurement with an OD of 1.21+0.02. 121/125 showed colour development as judged by eye corresponding to an OD of 0.16+0.09. The PPV was 96.8%. There was no interobserver variability. Limitation of the methods is the lack of sure information about the compliance of the patients. Further validation of the POC method is ongoing.

Under real life conditions the POC method and judgement of colour development by eye increased the PPV and NPV from about 85% using plasma samples to more than 95% using urine samples for determination of rivaroxaban. The method is non-invasive, rapid, and specific, can be repeatedly performed and may be used by medical personal and patients. Colour development differs from the POC method for dabigatran from urine samples of patients on treatment.