Measuring Direct Oral Anticoagulant Levels in Laboratory Practice: Impact of Different Storage Conditions of Blood Samples

Background: Direct oral anticoagulants (DOACs) have simplified anticoagulant therapy, but plasma level testing (i.e., anti-Xa and anti-IIa activities) remains important in specific clinical situations (e.g., emergency surgery, bleeding, renal impairment, or suspected non-adherence). However, the impact of sample storage on assay reliability is not well defined. This study evaluated the stability and potential systematic errors in DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) plasma levels after 24 h storage under different conditions. Methods: We enrolled 182 patients on one of the four DOACs. Blood samples were collected in duplicate citrated tubes. The first tube was processed within 4 h to obtain baseline values, with plasma successively stored at room temperature, 4°C, and −20°C for 24 h. The second tube was stored as whole blood at room temperature before measuring DOACs concentrations. DOACs were measured using dedicated clotting or chromogenic assays. Stability was assessed using non-parametric statistics, Passing-Bablok regression, and Bland–Altman analysis, with Acceptable Change Limits based on assay variability. Results: All DOACs showed good stability across conditions, with median recoveries ranging from 93% to 102%. No significant proportional errors were observed. Minor constant biases were observed for apixaban (at 4°C and −20°C), and more consistently for rivaroxaban and edoxaban. Dabigatran showed no significant bias. Variability was generally low (< 7%), and most measurements near clinical thresholds remained accurate. Conclusion: DOACs plasma levels remain stable after 24 h storage under various conditions. While minor biases exist, particularly for rivaroxaban and edoxaban, they are unlikely to affect clinical interpretation in most cases. Whenever needed, DOACs measurement can be deferred after blood drawing without jeopardizing results interpretation.