Measurement of rivaroxaban and apixaban in serum samples of patients

Abstract

Background: The determination of rivaroxaban and apixaban from serum samples of patients may be beneficial in specific clinical situations when additional blood sampling for plasma and thus the determination of factor Xa activity is not feasible or results are not plausible.

Materials and methods: The primary aim of this study was to compare the concentrations of rivaroxaban and apixaban in serum with those measured in plasma. Secondary aims were the performance of three different chromogenic methods and concentrations in patients on treatment with rivaroxaban 10 mg od (n = 124) or 20 mg od (n = 94) or apixaban 5 mg bid (n = 52) measured at different time.

Results: Concentrations of rivaroxaban and apixaban in serum were about 20-25% higher compared with plasma samples with a high correlation (r = 0·79775-0·94662) using all assays (all P < 0·0001). The intraclass correlation coefficients were about 0·90 for rivaroxaban and 0·55 for apixaban. Mean rivaroxaban concentrations were higher at 2 and 3 h compared with 1 and 12 h after administration measured from plasma and serum samples (all P-values < 0·05) and were not different between 1 vs. 12 h (plasma and serum).

Conclusions: The results indicate that rivaroxaban and apixaban concentrations can be determined specifically from serum samples.

Keywords: Apixaban; chromogenic substrate methods; direct oral anticoagulants; plasma; rivaroxaban; serum.

Figure 1

Boxplots of plasma (open boxes) and serum (stippled boxes) concentrations of rivaroxaban at 12 h after administration of 10 mg rivaroxaban od for 4–6 days in patients with elective hip or knee replacement surgery.

Figure 2

(a–c) Boxplots (S2222 chromogenic substrate method, (a) Coamatic chromogenic substrate assay, (b) and HemosIL chromogenic substrate assay, (c) of plasma (open boxes) and serum (stippled boxes) concentrations of rivaroxaban at 1, 2, 3 and 12 h following administration of 20 mg rivaroxaban od at steady state levels. Samples were taken from patients at different outpatient visits at indicated time intervals after intake of medication. P-values are given in Table 3.

Figure 3

Boxplots of plasma (open boxes) and serum (stippled boxes) concentrations at 12 h following administration of 5 mg apixaban bid at months 3–6 in patients with atrial fibrillation or prevention of recurrent venous thromboembolism. Concentrations were measured using different chromogenic substrate assays.