Abstract
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.
Keywords
rivaroxaban - prothrombin time assay - activated partial thromboplastin time - thromboplastin
reagent - prothrombinase-induced clotting time assay - chromogenic substrate methods