Quality performance for indirect Xa inhibitor monitoring in patients using international external quality data

Abstract

ObjectivesChromogenic anti-activated factor X (FXa) assays are currently the “gold standard” for monitoring indirect anticoagulants. However, anti-FXa has been shown to vary according to the choice of reagents. In the present study, the performance of anti-FXa measurement was evaluated in order to gain more insight into the clinical applications. Furthermore, the longitudinal coefficient of variation (CV) was studied to investigate whether there is improvement over time.MethodsLaboratory tests results were evaluated for samples spiked with unfractionated heparin (UFH), low-molecular-weight-heparin (LMWH), fondaparinux and danaparoid sodium. External quality assessment (EQA) data from multiple years were used from more than 100 laboratories.ResultsComparison of the results for all methods showed significant differences in measured values between the frequently used methods (ANOVA: p < 0.001). The largest differences were observed for LMWH and UFH measurements. These differences may be caused by differences in method composition, such as the addition of dextran sulphate. Substantial interlaboratory variation in anti-FXa monitoring was observed for all parameters, particularly at low concentrations. Our results showed that below 0.35 IU/mL, the CVs for UFH and LMWH increase dramatically and results below this limit should be used with caution.ConclusionsOur study demonstrates that the choice of the anti-FXa method is particularly important for UFH and LMWH measurement. The variation in measurements may have an effect on clinical implications, such as therapeutic ranges. Furthermore, the longitudinal EQA data demonstrated a constant performance and, in at least 50% of the cases, improvement in the CV% of the anti-Xa results over time.

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory

“…Unlike a 'global' test like APTT, the measurement of anti-Xa activity is insensitive to fluctuations in the underlying hemostatic state (for example, coagulation factor defect following hemorrhage or DIC), which should prompt an adjustment in therapeutic targets to the clinical context and the possible identification of such defects. Finally, significant variability in heparin sensitivity has been reported between the different commercial kits [153][154][155][156].…”

Studies on hemostasis in COVID‐19 deserve careful reporting of the laboratory methods, their significance, and their limitations

“…First, a high variability in heparin plasma levels measurements between the available anti-Xa kits has been reported, especially for unfractionated heparin (UFH) and for low anti-Xa levels. 2 The authors did not specify the kit they used. If they have used a reagent that contains dextran sulfate (as most currently available reagents do), this could have led to an overestimation of the heparin levels.…”

“…First, a high variability in heparin plasma levels measurements between the available anti‐Xa kits has been reported, especially for unfractionated heparin (UFH) and for low anti‐Xa levels 2 . The authors did not specify the kit they used.…”

Response to “Studies on hemostasis in COVID‐19 deserve careful reporting of the laboratory methods, their significance and their limitation”: Don’t throw the baby out with the bathwater

“…We used HemosIL Liquid anti‐Xa kit (Werfen, Le Pré‐Saint‐Gervais, France) containing dextran sulfate but no exogenous antithrombin. It is indeed true that different anti‐Xa methods can give different results 2 . The anti‐Xa methods that are the least influenced by plasma proteins, ie, with dextrans and appropriate dilution, approach the plasma concentration best.…”