Abstract Number: PB0555
Meeting: ISTH 2020 Congress
Background: Portola Pharmaceuticals has developed Bevyxxa® a direct factor-Xa inhibitor approved in the US for the venous thromboembolism prophylaxis in medically ill patients. Bevyxxa® is mainly excreted via the bile and has a low renal clearance. The plasma concentration of this drug has been estimated to be approximately ten times less than other factor-Xa inhibitors. An inhibitor-specific Anti-Xa assay may be used to assess Bevyxxa® Anti-Xa activity.
Aims: Proof of concept for the determination of Bevyxxa® concentration in plasma with specific calibrators and controls using STA-Liquid anti-Xa on STA-R Max.
Methods: The assay was optimized using commercial STA-Liquid anti-Xa and two Stago analysers. Assay calibration and quality control (QC) recovery were performed with specific freeze dried calibrator and controls respectively. Normal pooled plasma spiked with seventeen levels of Bevyxxa® were tested. Six ex-vivo samples from Bevyxxa® study were also tested. The following parameters were determined.
- Limit of blank (LoB) using five normal pooled plasma samples.
- Limit of detection (LoD) and linearity limit using Bevyxxa®-spiked plasma (n=8).
- Day-to-day precision (at least 5 series) using two levels of QC and two other levels of Bevyxxa®-spiked plasma.
- Accuracy measurement according to LC-MS reference method using Bevyxxa®-spiked plasma and ex-vivo samples.
- Long term stability of freeze dried calibrator and QC.
Results: Results are summarized in the table I.
Conclusions: This new Bevyxxa® Anti-Xa activity assay automated on STA-R Max is accurate in the 8-110ng/mL range and reproducible with STA-Liquid Anti-Xa using new specific freeze-dried calibrator and controls. This is the very first study with Bevyxxa® samples and Stago commercial system. The results with ex-vivo samples showed good agreement with LC-MS reference method.
|ITEM||Stago Bevyxxa® Anti-Xa Assay|
|Limit of blank (LoB)||5.5 ng/mL|
|Limit of detection (LoD)||8.0 ng/mL|
|Linearity||Relative deviation from linearity (DLi) is less than 15% within the 15-110 ng/mL Bevyxxa® range. Absolute DLi is less than 2.5 ng/mL in the low range (< 15 ng/mL)|
|Day-to-day precision||Maximum CV of 10% with 10-20-30-60 ng/mL Bevyxxa® samples|
|Accuracy||Good agreement between Stago modified assay and LC-MS reference method on spiked and ex-vivo samples: Mean relative difference with LC-MS is below 16% within the 15-110 ng/mL Bevyxxa® range. Mean absolute difference with LC-MS is below 3 ng/mL in the low range (< 15 ng/mL)|
|Long term stability||Freeze-dried Bevyxxa® calibrators and controls stable up to 33 months at 2-8°C.|
[Summary of Stago assay performances.]
To cite this abstract in AMA style:Bourdin M, Perrotin D, Mathieu O, Herve T, Depasse F, Lu G. Modified Anti-Xa Assay for Measuring Betrixaban (Bevyxxa®) Activity in Plasma on STA-R Max [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/modified-anti-xa-assay-for-measuring-betrixaban-bevyxxa-activity-in-plasma-on-sta-r-max/. Accessed November 30, 2021.
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