Monitoring unfractionated heparin therapy: Lack of standardization of anti-Xa activity reagents

Abstract

Introduction: One of the main advantages of using anti-Xa instead of activated partial thromboplastin time in monitoring of unfractionated heparin (UFH) therapy relies on its hypothesized standardization, with a unique therapeutic range defined to be 0.30 to 0.70 IU/mL. The aim of the present study was to compare the inter-reagent agreement of anti-Xa activity.

Methods: Citrate tubes were obtained from 104 inpatients on UFH. Plasma samples were stored frozen in aliquots at -70°C before being shipped to three accredited coagulation laboratories to be evaluated for anti-Xa activity using their routine assay(s). Pooled normal plasmas spiked with dilutions of the 6th International Standard of UFH to achieve anti-Xa activities up to 1.0 IU/mL were evaluated using the same techniques.

Results: In the plasmas from patients on UFH, the median anti-Xa activity ranged from 0.37 IU/mL with one reagent to 0.57 IU/mL with another; results were in between (0.45 IU/mL) using two other reagents. Comparisons of results obtained using the different reagents demonstrated unacceptable bias up to 0.24 IU/mL between some reagents (41% difference). The concordance as whether anti-Xa activities measured using different reagents were within or outside the therapeutic range was between 0.411 and 0.939 (kappa). Similar discrepancy was demonstrated for anti-Xa activities when evaluating normal plasma spiked with the International Standard. A discrepancy of the same order of magnitude was demonstrated in the 2017 External Quality Assessment Program provided by the External Quality Control in Assays and Tests exercises.

Conclusions: The reported discrepancy between test results obtained using different anti-Xa assays clearly suggests a lack of standardization of that assay with potentially significant impact on the patients' anticoagulation.

Keywords: aPTT; anti-Xa activity; monitoring; standardization; unfractionated heparin.