Global coagulation assays to measure in vitro fibrinolysis

Abstract

Fibrinolysis is a critical component of hemostasis associated with poor outcomes if not treated early and effectively. Successful hemostasis management requires close fibrinolysis monitoring. The study aimed to compare the fibrinolysis detection capabilities of different viscoelastic hemostatic analyzers (VHA) and assays, including the new generation cartridge-based devices, and D-dimers under standardized conditions in vitro . Tissue plasminogen activator (tPA) induced fibrinolysis was assessed with D-dimers, TEG®6s (new generation; n = 160 samples) and TEG®5000 (older generation; n = 140 samples) at 30 min after maximum amplitude (MA, LY30) for the RapidTEG® (CRT) and Kaolin (CK) assays, and at 30 min after clotting time (CT; LI30) for the ROTEM® Sigma and ROTEM® Delta (new and older generations, n = 160 and n = 140 respectively) INTEM and EXTEM assays. Both VHA analyzers showed a monotonic relationship between lysis at 30 min and increased tPA concentrations. D-dimers had the highest sensitivity for detecting fibrinolysis compared with the VHA assays, however they had lower specificity at the highest tPA concentrations. Variance between duplicate measurements in the new generation devices was 1.6–3.7% for TEG®6s and 11.9–15.8% with ROTEM® Sigma. All VHA devices identified lower fibrinolysis levels than currently used in published treatment algorithms. Differences were observed between intrinsic versus extrinsic pathway activated assays in the ability to detect tranexamic acid fibrinolysis reversal. The results show that while D-dimers are more sensitive at detecting in vitro fibrinolysis, VHA devices could be used as a fast, effective, and portable alternative to detect fibrinolysis rapidly, with high sensitivity and specificity. • Viscoelastic hemostatic analyzers (VHA) can be used to detect fibrinolysis. • New and old generation VHA detected induced fibrinolysis with high sensitivity and specificity. • D-dimers had the highest sensitivity for detecting fibrinolysis, but lower specificity. • Current VHA fibrinolysis detection thresholds could be optimized for patient treatment.