Abstract Background Rivaroxaban is direct anti-FXa oral anticoagulant indicated for the prevention of venous thromboembolic events (VTE) in patients who have had orthopedic surgery, prevention of stroke and embolism in patients with atrial fibrillation, deep vein thrombosis (DVT) and pulmonary embolism (PE) treatment. Rivaroxaban is also indicated to reduce the risk of cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Due to the use of this drug across the regional patient population, our hospital system decided to validate a rivaroxaban test for urgent clinical situations. Some of these situations include trauma patients, especially those with potential renal dysfunction. Rivaroxaban is cleared by the liver and kidneys, and clearance may be delayed in patients with renal and liver dysfunction. Rivaroxaban can be measured with a chromogenic anti-Xa assay using drug specific calibrators and controls, reporting in gravimetric units (ng/ml). The objective of the study was to validate a test that could measure the levels of rivaroxaban in sodium citrate plasma for our automated coagulation analyzers using criteria for validation of laboratory developed tests (LDTs). Methods We used guidance from the CAP (College of American Pathologists) checklist COM.40350 to guide our validation protocol. The validation procedure included: analytical accuracy, precision, reportable range to include lower limit of detection, interfering substances assessment, linearity, and carryover. Standard data analysis programs and were used to assess data acceptability, while following manufacturer recommendations. STA Rivaroxaban Calibrator, STA Rivaroxaban Control, and STA Liquid Anti-Xa reagents were run on a STA R MAX automated coagulation analyzer using standard operating procedures as provided by the manufacturer, by certified and trained medical laboratory professionals (Diagnostica Stago, Inc., Parsippany, NJ). A combination of 32 specimens were used for our study, including remnant plasma from known patients taking rivaroxaban along with BIOPHEN rivaroxaban quality control plasmas from Aniara Diagnostica (West Chester, OH). 42 known rivaroxaban patient and quality control plasmas were used to establish correlation between two different STA R MAX analyzers. Known samples covered the full reportable range of 10-500 ng/ml. Interfering substances were determined by spiking known value target samples with food coloring and unfractionated heparin to mimic slight, moderate, and high levels of interfering substances. Results Method comparability between two different STA R MAX instruments produced an R Value= 0.99. Intra-run and total precision were measured using quality control plasmas, with both observed % CV 5.0 (see table). Rivaroxaban quality control samples spiked with heparin showed interference with the rivaroxaban results (not shown). Interfering substance determination showed any amount of hemolysis in the sample interferes in the assay, but slight amounts of icterus or lipemia can be tolerated without adversely affecting the result (not shown). Carryover assessment was also performed and determined acceptable using the rivaroxaban quality control plasmas (not shown). Conclusion Our laboratory was successfully able to validate Rivaroxaban as a laboratory developed test. An interpretative comment appended to the result provides information for ordering clinicians, developed in collaboration with our hospital pharmacy division.
Hoesl et al. (Wed,) studied this question.