Evaluation of Global Hemostatic Assays in Response to Factor VIII Inhibitors

Abstract

Global hemostatic assays including thromboelastography (TEG), Innovance ETP (endogenous thrombin potential), and Thrombinoscope could measure thrombin generation potential and be useful to guide management of patients with factor VIII (FVIII) inhibitors. However, the performance characteristics of these global assays in the presence of FVIII inhibitors are incompletely characterized. In this study, the normal range of thrombin generation potential was measured in 20 healthy individuals by all 3 assays. In 5 commercial and 7 clinical samples with FVIII inhibitors, it was shown that PPP-reagent thrombinoscope shows a dose-dependent response to different levels of FVIII inhibitors from the same patients, while Innovance ETP shows virtually no response to FVIII inhibitors. The TEG is more sensitive to FVIII inhibitors than thrombinoscope. Importantly, we show the same levels of FVIII inhibitor from different patients results in different levels of inhibition for thrombin generation potential by thrombinoscope, which potentially explains the phenotypic heterogeneity of patients with FVIII inhibitors. Global assays such as thrombinoscope, but not Innovance ETP, show appropriate sensitivity to FVIII inhibitors that could offer an objective and clinically relevant marker to guide patient management.