Etude Comparative Entre Dosage Anti-xa Spécifique Des Aod Et Activité Anti-xa Calibrée À L’héparine

Abstract

Direct oral anticoagulants (DOACs) that inhibit factor Xa, namely rivaroxaban and apixaban, are widely prescribed for the prevention and treatment of thromboembolic diseases. However, in the Algerian context, specific plasma assay of these molecules remains limited due to the small number of hemobiology laboratories equipped for this purpose and the high cost of specific calibrators. In practice, many laboratories therefore resort to heparin-calibrated (LMWH) anti-Xa assays as an alternative, without sufficient local validation of their performance for estimating DOAC concentrations. In this context, our study aims to evaluate the analytical performance and clinical concordance of the heparin-calibrated anti-Xa method compared with the assay using DOAC-specific calibrators. This retrospective analytical study, conducted at the hemostasis laboratory of the University Hospital Center (CHU) of Sétif (December 2025 – May 2026), included 27 patients on rivaroxaban (n = 11, 40.7%) and apixaban (n = 16, 59.3%), with a mean age of 68.22 ± 13.99 years. A total of 54 paired measurements, performed at pharmacological peak and trough, were obtained using two chromogenic anti-Xa methods on a STA Compact Max® analyzer: the reference method with specific calibrators (results in ng/mL) and the hybrid method with hybrid heparin calibrators (results in IU/mL). The analytical performance of the two methods was assessed using Spearman correlation, linear regression, Cohen's kappa coefficient, and ROC analysis (significance threshold: p < 0.05). A strong overall correlation was observed between the two methods (ρ = 0.802; p < 0.001). At trough, the correlation was significant for rivaroxaban (ρ = 0.773; p = 0.005) and apixaban (ρ = 0.612; p = 0.012), with a coefficient of determination R² = 0.797 for rivaroxaban. In contrast, at peak, the correlations were not significant for either molecule, due to systematic saturation of the hybrid heparin calibrator. Concordance of therapeutic classifications was moderate for rivaroxaban at trough (κ = 0.450) and null for apixaban at trough (κ = 0.000). ROC analysis revealed perfect diagnostic performance of the hybrid method for apixaban at trough (AUC = 1.000) and moderate performance for rivaroxaban at trough (AUC = 0.667). The heparin-calibrated anti-Xa method represents a useful screening tool for assessing residual DOAC concentrations in emergency settings, but cannot replace specific calibrators for precise quantification, particularly at pharmacological peak. Standardization of decision thresholds and larger-scale multicenter studies are needed to optimize its integration into Algerian hospital biological practice