Abstract Number: PB0659
Meeting: ISTH 2020 Congress
Background: Thrombin generation (TG) assessed by Calibrated Automated Thrombogram (CAT-I) reflects the overall capacity of plasma to generate thrombin, thus evaluating the balance between the anti- and procoagulant processes. However, with this method the calibrator curve is usually not measured until completion which has a severe impact on the calculation of the TG parameters, especially under conditions where almost all substrate is consumed. Additionally, direct thrombin inhibitor (DTI) cannot be present in the calibration sample due to inhibition of the calibrator.
Aims: Development of a modified TG assay (CAT-II) and its comparison head to head with the CAT-I method using the same fluorometer.
Methods: TG was assessed with CAT-I and CAT-II in control plasma and plasma containing different anticoagulants (dabigatran, rivaroxaban, apixaban). In CAT-I, measurements were calibrated against the same plasma containing calibrator in the presence of fluorogenic substrate(Z-GGR-AMC). In contrast, CAT-II method used a standard concentration of thrombin in buffer and AMC in a separate plasma sample for calibration thereby not being influenced by the presence of DTI.
Results: TG obtained from CAT-I and CAT-II using anticoagulant free plasmas appeared to be identical with intra-assay variations less than 5% concerning all measured parameters (lag time, peak height, endogenous thrombin potential). When comparing the two different calibration methods in the presence of different anticoagulants, a high correlation was seen in the presence of rivaroxaban and apixaban (R2>0.97), but not with dabigatran, a direct thrombin inhibitor. CAT-II method showed dose-dependent inhibition of TG in the presence of dabigatran, while CAT-I was not able to detect it. Furthermore, hemoglobin or bilirubin does not interfere with the results of CAT-II.
Conclusions: Our results showed that there is no difference between the results of CAT-I and CAT-II method when it is applied in control plasmas, while the CAT-II method is able to correctly measure samples containing direct thrombin inhibitor.
To cite this abstract in AMA style:Giesen PLA, Gulpen A, van Oerle R, ten Cate H, Nagy M, Spronk HM. Calibrated Automated Thrombogram II: A New Thrombin Generation Test [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/calibrated-automated-thrombogram-ii-a-new-thrombin-generation-test/. Accessed March 4, 2024.
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