# Dynamic and Quantitative Assessment of Blood Coagulation Status with an Oscillatory Rheometer
## 4 Discussion
For instance, the oscillatory rheometer identified all heparin/protamine concentrations as significantly different except the equimolar concentration when measuring clotting times (see Figure A9). In contrast to that, the ball coagulometer could not differentiate between equimolar heparin/protamine and 2.0 IU/mL heparin with 1.5 IU/mL protamine. The oscillatory rheometer (see Figure A10a,b) provided significantly different results (e.g., 2.0 IU/mL heparin/1.5 IU/mL protamine) for the linear slopes (clot formation) and the elastic shear modulus at the end of the measurement (maximum clot firmness). This example shows that further parameters can facilitate the interpretation of medical parameters in clinical practice. Further, it might be possible to detect clinical conditions that do not influence the clotting time (e.g., a slight thrombocytopenia), but have an influence on the clot formation and the clot firmness. So the rheometer was capable to detect the back titration of heparin with protamine which is normally performed with the Haemostasis Management system (HMS). That device determines the level of heparin in the blood, based on a titration with the heparin antagonist protamine. According to [PERSON], the equimolar concentrations of heparin and protamine provided the lowest clotting time [25]. A deficit and also a surplus of protamine lead to prolonged clotting time. This is due to the surplus of protamine exhibiting an anticoagulant activity itself by inhibiting factor V activation [26]. This phenomenon could be also observed within the oscillatory rheometer measurements, a surplus of protamine, led to a prolonged clotting time, the linear slopes and the viscous and elastic shear moduli were lower than in the control measurement. Currently, there are standardly used clotting measurements devices on the market (e.g., the simple KC 1A or sophisticated ROTEM) and also newer devices in their research phase. One example of a novel clotting measurement was reported by [PERSON] et al. [27]. The resonant acoustic spectroscopy with optical vibrometry (RASOV) measures the clot elastic modulus (CEM in kPa) via acoustic spectroscopy. A magnetic force produces a vibration to the sample surface and the result is a specific resonant frequency. Their study showed that the system is sensitive to various fibrinogen contents and is capable to assess different CEM of purified clots formed with varying amounts of fibrinogen and thrombin. On the one hand, the RASOV has the potential to analyse the clot structure, composition and its functional mechanical properties, but on the other hand it is not able to measure coagulation dynamics like the oscillatory rheometer in this study [27]. Despite several attempts to establish free oscillation rheometry, the Rotational thromboelastometry (ROTEM) remains the gold standard for sophisticated haemostasis monitoring [28]. It is a medical device that is currently used in clinical practice [29; 30; 31]. The ROTEM uses a fixed cuvette (Cup) with a cylindrical pin that is immersed into the cup filled with whole blood (gap of 1 mm). The movement of the rotating pin is restricted once the blood starts clotting. This is detected by a spring affixed to the pin. The kinetic change is detected optically by an integrated computer (TEMogram). Using several cuvettes at a time with different reagents, it is able to measure the interactions of coagulation factors, inhibitors and cellular components during the phases of clotting and subsequent lysis over time [32; 33; 34]. Compared to the ROTEM, Kinexus Pro provided also information on the coagulation process over time in dependence of the chosen coagulation assay and of various inhibitor concentrations. Furthermore, the rheometer is also capable to provide the clotting time (CT) and the clot firmness at a certain time point. In contrast to the oscillatory rheometer, ROTEM just measures the elasticity of the blood sample, but does not provide information on the shear moduli.