Determination of rivaroxaban in human plasma samples.

Rivaroxaban is one of the novel oral direct factor Xa inhibitors, which is effective in preventing thromboembolic complications at fixed doses (i.e., once daily), without the need for dose adjustment according to laboratory monitoring. Nearly 60% of rivaroxaban is cleared from circulation by glomerular filtration, 30% of which is excreted as active drug. Therefore, as renal elimination plays a pivotal role in the metabolism of this drug, impairment of renal function may be important during anticoagulation with rivaroxaban over long periods of time. The assessment of the anticoagulant effect/concentration of rivaroxaban may thus be useful in special patient populations such as in the elderly and eldest, during acute diseases with concurrent dehydration, before surgery, during bleeding or thrombotic episodes, or to verify adherence to therapy. Rivaroxaban prolongs prothrombin time in a dose-dependent, linear fashion. Activated partial thromboplastin time (APTT) is also prolonged, but in an exponential manner. Substantial differences in test results might be generated by different thromboplastin and APTT reagents. One-step prothrombin-induced clotting time assay is sensitive to low concentrations of rivaroxaban. Chromogenic substrate assays specific for factor Xa are also sensitive to rivaroxaban. Several initiatives are currently ongoing to standardize the various methods to determine rivaroxaban in human plasma samples, some of which will be summarized in this article along with the dose-dependent effects of rivaroxaban on relevant coagulation parameters. Therefore, although rivaroxaban prolongs all coagulation assays used to assess the anticoagulant effects of most anticoagulants, the most specific assay cannot be identified at present. Moreover, clinical trials are needed to determine the relationship of assay results with bleeding or thrombotic complications.

Determination of the anticoagulant effects of new oral anticoagulants: an unmet need.

Thromboembolic diseases require anticoagulation for their prevention and treatment. New oral anticoagulants, specifically direct factor Xa and thrombin inhibitors, were developed to overcome the limitations of conventional anticoagulants. Their benefit has been demonstrated using fixed doses without laboratory-guided dose adjustment for patients following elective knee and hip replacement, treatment of venous thromboembolism and prevention of embolic events in atrial fibrillation. These anticoagulants are excreted by glomerular filtration at a rate of between 25 and 80%. Thus, lower doses are required for patients with impaired renal function. Therefore, determination of the anticoagulant effects may be needed in other specific patient populations. Prothrombin time, activated partial thromboplastin time, prothrombin-induced clotting time, ecarin clotting time, hemoclot assay, other specific coagulation assays and chromogenic substrate are available to determine the effect of the anticoagulants. Standardization of methods, development of point-of-care tests and identification of patient groups is ongoing.