Abstract Number: PB0703
Meeting: ISTH 2020 Congress
Background: Thrombin generation (TG) test is a global hemostasis assay potentially suitable for detection of procoagulant conditions caused by elevated coagulation factor activity. However, commercially available TG assays may underestimate elevated TG in cases when fluorogenic substrate for thrombin is depleted or fluorescence is attenuated by the inner filter effect. An artifact correction approach called Calibrated Automated Thrombogram (CAT) is available but it remains unknown whether correction is either needed or sufficient to detect elevated TG.
Aims: We analyzed substrate depletion and its effect of TG parameters in plasma samples with elevated coagulation factor levels or reduced antithrombin, tested by commercial CAT platform.
Methods: CAT experiments and in-house software capable of internal thrombin calibration with or without substrate artifact correction.
Results: An increase in the Thrombin Peak Height (TPH) and Endogenous Thrombin Potential (ETP) after 2x- or 4x-fold increase in factors V, VIII, IX, XI, or prothrombin was detected in the presence and absence of artifact correction. CAT algorithm applied correction to every sample regardless of their procoagulant potential, decreasing TPH in low procoagulant samples by up to 10% and increasing TPH in all factor supplemented samples (except prothrombin) by up to 18%. Consistently, substrate was not consumed except in samples with elevated prothrombin or decreased antithrombin. For these highly procoagulant samples, uncorrected TPH or AUC values were underestimated and, in some cases, comparable to normal range, but application of CAT correction algorithm produced inconsistent or missing TG curves because of the failure of correction algorithm. Each sample that was poorly resolved by uncorrected or CAT correction analyses was characterized by the substrate depletion algorithm proposed in this work.
Conclusions: Our data suggest that substrate consumption correction algorithms are neither necessary nor sufficient for detection of extremely procoagulant samples, and can be replaced with a much simpler screening for substrate depletion.
To cite this abstract in AMA style:Chang W, Machlus K, Wolberg A, Ovanesov M. Algorithm for Detection of Procoagulant Samples with Elevated Prothrombin and Reduced Antithrombin by their Ability to Deplete Fluorogenic Thrombin Substrate [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/algorithm-for-detection-of-procoagulant-samples-with-elevated-prothrombin-and-reduced-antithrombin-by-their-ability-to-deplete-fluorogenic-thrombin-substrate/. Accessed November 26, 2020.
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