Detection of tPA-induced hyperfibrinolysis in whole blood by RapidTEG, KaolinTEG, and functional fibrinogenTEG in healthy individuals

Abstract

Background: Rapid identification of clinically relevant coagulopathies in, acute coagulopathy of trauma shock (ACOTS) has led to the development of faster point-of-care viscoelastic whole-blood-based tests like rapid thrombelastography (RapidTEG). The sensitivity of RapidTEG to detect hyperfibrinolysis, as compared to standard KaolinTEG, is unknown. To investigate this, the ability of RapidTEG, KaolinTEG, and functional fibrinogenTEG (FFTEG) to detect tPA-induced (tissue plasminogen activator) lysis in whole blood from healthy individuals was investigated. Our hypothesis was that the initial powerful clot formation in the RapidTEG assay would reduce the sensitivity as compared to the normally used KaolinTEG assay. We also evaluated the FFTEG assay.

Methods: In vitro comparison of the sensitivity of RapidTEG, KaolinTEG, and FFTEG to 1.8 nmol/L tPA in citrated whole blood (299 ± 23 ng/mL plasma) induced hyperfibrinolysis in 10 healthy individuals and duplicate titration of the tPA whole blood (WB) concentration from 0.09 to 7.2 nmol/L (14-1144 ng/mL plasma) in 1 healthy donor.

Results: At 1.8 nmol/L tPA, KaolinTEG, RapidTEG, and FFTEG all detected fibrinolysis but with different sensitivities. In the titration study, KaolinTEG and FFTEG displayed a continuous dose-response association and RapidTEG also displayed a dose-dependent response but only for higher levels of tPA, thus yielding a smaller "dose-sensitive range" compared to KaolinTEG and FFTEG.

Conclusion: This pilot study demonstrated that KaolinTEG, RapidTEG, and FFTEG all were able to detect lysis at 1.8 nmol/L tPA but with a difference in sensitivity. Furthermore, KaolinTEG and FFTEG showed a continuous dose dependence related to the tPA concentration, whereas RapidTEG only detected lysis at higher tPA concentrations.