Monitoring of heparin therapy beyond the anti-Xa activity assay: Evaluation of a thrombin generation assay

Introduction: Global coagulation assays may be of added value to the anti-Xa assay for monitoring heparin therapy. Unlike most testing methods, the thrombin generation assay ( TGA) has the ability to assess the overall function of the hemostatic system, which provides information on the anticoagulation status of patients. We compared the TGA, measured with ST Genesia (R) STG-DrugScreen (R) reagent, with the anti-Xa assay for monitoring heparin therapy in inflammatory and non-inflammatory patients. We also determined reference values for STG-DrugScreen (R) thrombin generation (TG) parameters. Methods: Reference values were determined on 120 healthy donors. Furthermore, a spiking experiment with unfractionated heparin (UFH) and low molecular weight heparin (LMWH) was performed, and samples of patients receiving UFH or LMWH were analyzed with ST Genesia (R) and the anti-Xa assay. Results: High discrepancy between TG parameters and anti-Xa activity was observed for low LMWH anti-Xa levels. TG parameters were affected in 36/46 (time to peak) to 42/46 (peak height) patients during UFH therapy with sub-target anti-Xa activity levels. Conclusion: TGA seems insufficiently sensitive for low concentrations of LMWH. There may be an added value of the TGA for monitoring UFH in so-called heparin-resistant patients. Therefore, the TGA has the potential to be introduced as an additional tool for monitoring heparin therapy.