During open-heart surgery, the status of hemostasis has to be constantly monitored to quickly and reliably detect
bleeding or coagulation disorders. In this study, a novel optimized piezo-based measuring system (PIEZ) for rheological monitoring of hemostasis was established. The applicability of the PIEZ for the evaluation of
nucleic acid-based drugs influencing coagulation was analyzed.
Thrombin aptamers such as
NU172 might be used during
extracorporeal circulation (ECC) in combination with a reduced
heparin concentration or for patients with
heparin-induced
thrombocytopenia (HIT). Therefore, the effect of the coagulation inhibiting
thrombin aptamer NU172 and the abrogation by its complementary
antidote sequence (AD) were investigated by this rheological PIEZ system. After the addition of different
NU172 concentrations, the coagulation of fresh human blood was analyzed under static conditions and using an in vitro rotation model under dynamic conditions (simulating ECC). The clotting times (CTs) detected by PIEZ were compared to those obtained with a medical reference device, a ball coagulometer. Additionally, after the circulation of blood samples for 30 min at 37 °C, blood cell numbers,
thrombin markers (
thrombin-
antithrombin III (TAT) and
fibrinopeptide A (FPA)) and a platelet activation marker (β-thromboglobulin (β-TG)) were analyzed by
enzyme-linked
immunosorbent assays (ELISAs). The increase of
NU172 concentration resulted in prolonged CTs, which were comparable between the reference ball coagulometer and the PIEZ, demonstrating the reliability of the new measuring system. Moreover, by looking at the slope of the linear regression of the viscous and elastic components, PIEZ also could provide information on the kinetics of the coagulation reaction. The shear viscosity at the end of the measurements (after 300 s) was indicative of clot firmness. Furthermore, the PIEZ was able to detect the abrogation of coagulation inhibition after the equimolar addition of
NU172 aptamer´s AD. The obtained results showed that the established PIEZ is capable to dynamically measure the hemostasis status in whole blood and can be applied to analyze
nucleic acid-based drugs influencing the coagulation.