APTT therapeutic range for monitoring unfractionated heparin therapy. Significant impact of the anti‐Xa reagent used for correlation

Introduction Unfractionated heparin (UFH) therapy is monitored by using the anti‐activated factor X (anti‐Xa) activity, or the activated partial thromboplastin time (APTT), which remains the most widely used assay. One of the main advantages of anti‐Xa relies on its hypothesized standardization, with a unique therapeutic range (0.30‐0.70 IU/ml) for all reagents, whereas APTT is influenced by numerous preanalytical and analytical parameters not related to the anticoagulant activity of UFH. Methods The aim of this study was to compare the anti‐Xa‐correlated APTT therapeutic ranges calculated using different combinations of APTT (n = 4) and anti‐Xa reagents (n = 4) in frozen citrated plasmas from 87 inpatients on UFH. Results The median APTT ratio ranged from 2.19 for the less sensitive to 3.23 for the most sensitive reagent, whereas the median anti‐Xa activity was between 0.37 IU/ml and 0.57 IU/ml. The APTT therapeutic ranges calculated to correlate with anti‐Xa activities between 0.30 and 0.70 IU/ml were found to be highly different from one combination of APTT reagent and analyzer to another. The same applied to the therapeutic range of a single APTT reagent calculated using different anti‐Xa assays performed on the same analyzer, leading to a lack of agreement as to whether a sample was classified as subtherapeutic, therapeutic or supratherapeutic in 8.0% to 23.0% of the patients, with kappa coefficients between 0.908 and 0.753. Conclusions These results suggest that the APTT therapeutic range calculated to correlate with anti‐Xa activities between 0.30 and 0.70 IU/ml is influenced not only by the APTT reagent, but also by the anti‐Xa reagent used for calculation.