Measuring the anticoagulant effects of target specific oral anticoagulants—reasons, methods and current limitations

Abstract

To simplify and optimize oral anticoagulation, new target-specific oral anticoagulants (TSOAs) have been developed. The direct thrombin-inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban are the first such compounds to receive approval in certain countries for various indications. Due to the predictable pharmacokinetic and pharmacodynamic profiles of these drugs, routine monitoring of patients receiving TSOA therapy has not been considered necessary. However, it has now been realized that in routine clinical settings, there are several situations where it may be prudent to assess the level of TSOA anticoagulation. Several studies evaluating the influence of TSOAs on various coagulation assays have been performed to identify systems that can be used to monitor these drugs. With a particular focus on dabigatran and rivaroxaban, we will describe and discuss the potential of several methods for measuring the anticoagulant effect of TSOAs, as well as their methodological limitations and the restrictions in transferring their results into clinical context.

Point-of-Care Coagulation Testing for Assessment of the Pharmacodynamic Anticoagulant Effect of Direct Oral Anticoagulant

“…However, in special patient populations, for example, in patients with acute deterioration of renal function, before acute surgical interventions, during unexpected bleeding or thrombotic events while on therapy with DOA, or if suspicion of overdose and intoxication occurs, assessment of DOA pharmacokinetics might be necessary 26,27 with assays enabling at least a semiquantification of drug concentrations.…”

Multi-analyte analysis of non-vitamin K antagonist oral anticoagulants in human plasma using tandem mass spectrometry

“…Monitoring of routine coagulation parameters is of limited use only, as the anticoagulant effect is described qualitatively, not quantitatively. Moreover, reagents for these tests differ in their sensitivities and between laboratories, complicating comparability and reproducibility [8,26] . Compared to specific coagulation assays that indirectly assess NOAC plasma concentrations -such as calibrated chromogenic anti-Xa assays for rivaroxaban and apixaban or a calibrated diluted thrombin time assay for dabigatran -LC-MS/MS provides direct quantitation, enables rapid multi-analyte analysis, and shows better performance especially in the lower concentration range [9 -11] .…”

Interpretation of coagulation test results under direct oral anticoagulants

“…However, plasma concentrations of DOAC have been investigated and listed in Table 2 [ [22][23][24]. Some patients' cohorts will benefit from monitoring DOAC therapy or from determination of plasma concentrations, even though outstanding questions have to be answered [25,26]. Assured is the fact that laboratory and clinical evaluation is useful in exclusion of an underlying bleeding tendency due to DOAC or renal insufficiency.…”