Assays for Monitoring Apixaban and Rivaroxaban in Emergency Settings, State-of-the-Art Routine Analysis, and...

Area of Science:

• Clinical Chemistry
• Pharmacology
• Laboratory Medicine

Background:

• Direct-acting oral anticoagulants (DOACs) like apixaban and rivaroxaban require reliable therapeutic drug monitoring.
• Existing monitoring methods, including anti-Xa assays and LC-MS/MS, vary in their application and performance.
• Home-based sample collection using dried blood volumetric absorptive microsamples (VAMS) offers patient convenience but requires method validation.

Purpose of the Study:

• To compare the performance of an automated anti-Xa chromogenic assay and a laboratory-developed LC-MS/MS method for monitoring apixaban and rivaroxaban.
• To evaluate LC-MS/MS analysis in both plasma and VAMS for DOAC monitoring.
• To assess the clinical laboratory's awareness of performance differences between these analytical methods.

Main Methods:

• Full validation of a laboratory-developed LC-MS/MS method for DOAC analysis.
• Cross-validation of anti-Xa chromogenic assay and LC-MS/MS using 60 patient specimens.
• Analysis of DOAC concentrations in plasma and VAMS, with development of suitable calibrators for VAMS.

Main Results:

• The anti-Xa chromogenic assay and LC-MS/MS method yielded discordant plasma concentrations for apixaban and rivaroxaban.
• Significant lack of agreement was observed between DOAC concentrations measured in plasma versus VAMS.
• Dried plasma and whole blood calibrators were suitable for VAMS analysis, enabling a seven-day run cycle.

Conclusions:

• Clinical laboratories must recognize the performance differences between anti-Xa and LC-MS/MS assays for DOAC monitoring.
• Discrepancies between plasma and VAMS measurements highlight the need for careful interpretation of results.
• Accurate VAMS analysis necessitates concurrent measurement of hematocrit to correct for potential variations.