Activated Partial Thromboplastin Time and Anti-Xa Measurements in Heparin Monitoring

Abstract

We examined the concordance of heparin levels measured by a chromogenic anti-Xa assay and the activated partial thromboplastin time (APTT) during unfractionated heparin therapy (UFH) and the biochemical basis for differences between these measures. We also investigated the endogenous thrombin potential (ETP) as a possible measure of anticoagulation. Paired measures of anti-Xa and APTT were performed on 569 samples from 149 patients on UFH. The anti-Xa values and the APTT were concordant in only 54% of measurements. One hundred twelve samples from 59 patients on UFH were assayed for APTT, anti-Xa, factor II, factor VIII, and ETP. Supratherapeutic APTT values but therapeutic anti-Xa results had decreased factor II activity. Subtherapeutic APTT but therapeutic anti-Xa values had high factor VIII activity. ETP correlated with anticoagulation status and UFH dose. In conclusion, factor II and VIII activity contributes to discordance between APTT and anti-Xa results. ETP measurements may provide an additional assessment of anticoagulation status.

A Systems Pharmacology Model for Predicting Effects of Factor Xa Inhibitors in Healthy Subjects: Assessment of Pharmacokinetics and Binding Kinetics

“…Consequently, it demonstrates that the anti‐FXa level may provide a more accurate assessment of anticoagulation. This observation agrees well with the suggestion to preferably use an anti‐FXa test and not a PT or aPTT test to evaluate anticoagulation 40, 45. The percentage of FXa inhibition has a relatively small inter‐individual variability because the anti‐Xa assay is directly based on enzymatic inhibition, which can be accurately measured using well‐defined chemical reagents that are not biologically derived.…”

“…For apixaban, however, the model is overpredicting the actual observed aPTT values (see Figure 3 d ). A possible reason might be the difference in thromboplastin reagent concentrations used in the rivaroxaban and apixaban clinical trials 40. Consequently, this may hamper the prediction of coagulation effects of different compounds.…”

“…However, unlike the relatively standardized PT testing, there is no standardization of reagents used for aPTT testing. The variation in coagulometers, the lot‐to‐lot variation of a given manufacturer's reagents, and the different buffers used in aPTT tests may significantly contribute to the varying results 25, 40, 46. It may be that for these reasons, the prediction for apixaban in the aPTT test was not good.…”

Comparison of the aPTT With Alternative Tests for Monitoring Direct Thrombin Inhibitors in Patient Samples

“…A recent study has shown that differences in the concentrations of several coagulation proteins (especially factor VIII) in patient plasma samples may explain this variability. 17 A number of hospitals, including our own, use the aPTT to monitor DTIs administered by continuous infusion. Given the questions raised about the use of the aPTT to monitor unfractionated heparin, there is reason to question whether a different method of monitoring parenteral DTIs should be used.…”

Mechanical circulatory support: balancing bleeding and clotting in high-risk patients

“…The ACT correlates poorly with the heparin dose. 33 Therefore, some centers use an anti-factor Xa level or aPTT to manage heparin. Whole blood assays including thromboelastography (TEG) and thromboelastometry (ROTEM) are used by some centers, but further studies to standardize these techniques are required.…”