Abstract Number: PB1094
Meeting: ISTH 2022 Congress
Background: The prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels.
Aims: We aimed to study the accuracy of PiCT to determine rivaroxaban, apixaban, and edoxaban drug concentrations and assessed whether clinically relevant drug levels could be predicted correctly.
Methods: This analysis was conducted as part of the Simple-Xa study, a prospective multicenter cross-sectional study including 932 patients treated with rivaroxaban, apixaban, or edoxaban. Citrated plasma samples were collected, and the Pefakit® PiCT was conducted on a Siemens Atellica Coag 360. Ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was done to determine drug concentrations. Cut-off levels were determined using receiver-operating characteristics curves (ROC) and sensitivities regarding clinically relevant drug concentrations calculated (30 mg L-1; 50 µg L-1; 100 µg L-1).
Results: Samples of 851 individuals were available for the current analysis (apixaban, n=414; rivaroxaban, n=373; edoxaban, n=64). The median age was 76 (IQR 66 to 83), and 360 patients were female (42.7%). The correlation (Spearman’s correlation coefficient) between PiCT and drug concentrations was 0.85 in case of rivaroxaban (95% CI 0.82, 0.88), 0.66 in apixaban (95% CI 0.60, 0.71), and 0.78 in edoxaban (95% CI 0.65, 0.86). The sensitivity to detect clinically relevant drug concentrations was 85.1% in case of 30 µg L-1 (95% confidence interval [CI] 82.0, 87.7; specificity 77.9, 95%CI 72.1, 82.7), 85.7% in case of 50 µg L-1 (95% CI 82.4, 88.4; specificity 77.3, 95% CI 72.5, 81.5), and 85.1% in case of 100 µg L-1 (95% CI 80.9, 88.4; specificity 73.2%, 95% CI 69.1, 76.9). The distribution of PiCT in patients with and without clinically relevant concentrations is shown in Figure 1.
Conclusion(s): Overall, the association of PiCT with rivaroxaban, apixaban, and edoxaban drug concentrations was moderate, but the majority of clinically relevant drug levels were predicted correctly.
Figure
Distribution of prothrombinase-induced clotting times in patients with and without clinically relevant concentrations of rivaroxaban, apixaban, and edoxaban. Ultra-high performance liquid chromatography-tandem mass spectrometry -LC-MS/MS- was used to determine drug concentrations. Optimal thresholds are given at 36.0 s, 39.6 s, or 46.1 s, respectively.
To cite this abstract in AMA style:
Sathanantham V, Studt J, Mendez A, Alberio L, Fontana P, Wuillemin W, Schmidt A, Graf L, Gerber B, Mäder G, Bovet C, Sauter T, Nagler M. Prothrombinase-induced clotting time for the measurement of rivaroxaban, apixaban, and edoxaban drug concentrations: a cross-sectional study [abstract]. https://abstracts.isth.org/abstract/prothrombinase-induced-clotting-time-for-the-measurement-of-rivaroxaban-apixaban-and-edoxaban-drug-concentrations-a-cross-sectional-study/. Accessed September 27, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/prothrombinase-induced-clotting-time-for-the-measurement-of-rivaroxaban-apixaban-and-edoxaban-drug-concentrations-a-cross-sectional-study/