PhD Scientific Days 2025

Health Sciences I.

Assessment of the correlation between apixaban plasma concentration and its clinical efficacy

Name of the presenter

János Domonkos Stubnya

Institute/workplace of the presenter

Semmelweis University, Department of Intensive Therapy

Authors

János Domonkos Stubnya¹, Hanna Szász², Anna Párkányi¹, Máté Berczi¹, Dalma Skultéti¹, Adrienne Fehér³, Gellért Karvaly³, András Kállai¹, János Fazakas¹

1: Semmelweis University, Department of Intensive Therapy
2: Semmelweis University, Faculty of Medicine
3: Semmelweis University, Department of Laboratory Medicine

Text of the abstract

Introduction: Apixaban (AP) exerts its anticoagulant effect through direct, reversible inhibition of activated factor X (FXa). While several methods are available to determine serum drug levels, the relationship between concentration and clinical effect remains uncertain.
Aims: To compare serum AP concentrations measured by mass spectrometry (MS) and chromogenic anti-FXa assays (Chr), and to assess the corresponding anticoagulant effects at the measured drug levels using viscoelastic testing (VET).
Methods: The study included patients who had previously received VET-guided thrombolysis for pulmonary embolism (PE) at the Central ICU of Semmelweis University between April 2022 and September 2023, and were treated with apixaban (2×5 mg/day) during follow-up. At 1-, 3-, and 12-month control visits, MS and Chr drug level measurements were performed, along with ClotPro® VETs (EX, IN, and RVV tests), both before and 2 hours after AP administration. Data were analyzed using GraphPad Prism software (Spearman correlation, Wilcoxon test, linear regression, Bland-Altman analysis).
Results: A total of 22 patients were enrolled, yielding 110 individual measurements in total. MS yielded significantly higher apixaban concentrations than Chr (median: 149 vs. 128 ng/mL, p < 0.0001), as confirmed by Bland-Altman analysis. MS levels showed a moderate and significant correlation with CT values in EX (r=0.6565) and IN (r=0.6331), and a strong correlation in RVV (r=0.7616). However, linear regression revealed only modest coefficients of determination (R²: EX=0.44; IN=0.3028; RVV=0.5219), suggesting non-linear relationships. Comparison of trough and peak AP levels revealed statistically significant CT prolongation across all three tests (p<0.0001 for EX, RVV and IN), though all CT values in the IN test remained within the normal range regardless of drug level.
Conclusions: MS provided consistently higher AP plasma levels than Chr. While RVV tests showed the strongest correlation between drug level and anticoagulant effect, the low R² values imply that one cannot reliably infer one from the other. The modest CT prolongation in IN assays raises the possibility that 2×5 mg apixaban may yield only prophylactic-level anticoagulation. Our results highlight the importance of functional monitoring in guiding personalized anticoagulant therapy.
Funding: 2024-2.1.1-EKÖP-2024-00004