Preliminary report: Measurement of apixaban and rivaroxaban in plasma from bleeding patients.

OBJECTIVES

The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, are used for anticoagulation treatment. Although biochemical monitoring is not required, severe bleedings caused by DOAC have been reported. We therefore evaluated the chromogenic assay Biophen DiXaI (Biophen) using plasma from non-bleeding patients in treatment with DOAC and on spiked plasma from patients with ongoing bleeding.

METHODS

The Biophen method was compared with an in-house reference method; liquid chromatography-tandem mass spectrometry (LC-MS/MS) using plasma spiked with the compounds ranging from 20 to 1500 μg/L. Furthermore, the methods were compared using plasma from non-bleeding patients in treatment with DOAC (n = 106). In addition, plasma was collected from patients not treated with DOAC, but with ongoing bleeding and tested in spiking experiments (n = 14).

RESULTS

Analysis of plasma from 106 patients receiving rivaroxaban (n = 91) or apixaban (n = 15) showed agreement and correlation between the methods. Measurement in spiked plasma from patients with active bleeding, however, revealed a 26% overestimation by the assay.

CONCLUSIONS

Our findings show that Biophen is suitable for measuring apixaban and rivaroxaban concentrations in plasma. However, our results in patients with active bleeding show an overestimation of 26%. This should be taken into account when assessing possible intoxication with apixaban and rivaroxaban in patients presenting with bleeding.