# Dynamic and Quantitative Assessment of Blood Coagulation Status with an Oscillatory Rheometer
## 4 Discussion  
In this study, an oscillatory rheometer was used to evaluate blood coagulation status in dependence of different coagulation activators and inhibitors. We are the first to investigate the applicability of the rheological measurements to the currently used coagulation parameters for intrinsic (activated partial thromboplastin time, aPTT), extrinsic (prothrombin time, PT) coagulation, heparin status and back titration of heparin with protamine. To our knowledge this has not been done as extensively as in our work. The rheometer could differentiate between extrinsic (PT) and intrinsic coagulation (aPTT) in a similar fashion as the reference system KC 1A. Here, the rheometer provided clotting times comparable to those measured with the ball coagulometer (KC 1A). As additional feature, the oscillatory rheometer provided linear slopes of elastic and viscous components that describe the kinetics of the coagulation process as the change of both shear moduli over time. The elastic and viscous shear moduli at a certain time point give information about the portion of each components in the fluid. In this work, we used the shear moduli at 300 s after addition of the coagulation activator Thromborel, which gave an indication of the firmness of the resulting blood clot. The clotting time of the oscillatory rheometer is comparable to the systems detecting the plasmatic coagulation (here ball coagulometer KC 1A). Furthermore, the change of shear moduli over time (linear slopes) and the shear moduli at a certain time point might be comparable to viscoelastic monitoring devices such as free oscillation rheology (FOR) [24] or the Rotational Thromboelastometry (ROTEM). Apart from simply differentiating between extrinsic and intrinsic coagulation, the oscillatory rheometer was able to differentiate between various heparin concentrations added to the blood samples. Overall, human whole blood in combination with coagulation activator or inhibitor has larger deviations (Kinexus Pro, coefficient of variation for e.g., citrated blood with Thromborel; \(\
u_{\rm 1 Hz}(\rm G^{\prime})=7.11\%\)) than calibration fluids (Kinexus Pro, coefficient of variation for e.g., xanthan 0.2%; \(\
u_{\rm 1 Hz}(\rm G^{\prime})=2.1\%\)), which is due to the biological variation even with the same donor (day-to day variability). During extracorporeal circulation, the contact of blood to the large foreign surface requires a relatively strong systemic anticoagulation. Therefore, the present heparin concentration should be monitored to timely react with the addition of further heparin if necessary. The results of the heparin and protamine titration showed that with the dynamic measurements of the oscillatory rheometer were \begin{table}
\begin{tabular}{l c c c c c c} \hline \hline
**Sample** & **Kinexus Pro** & **KC 1A** & **Kinexus Pro** & & \\ \hline  & **CT/s** & **CT/s** (KC 1A)** & **G\({}^{\prime}\) (Pa)** & **G\({}^{\prime\prime}\) (Pa)** & **m** (G\({}^{\prime}\)/Pa.s\({}^{-1}\)) & **m** (G\({}^{\prime\prime}\)/Pa.s\({}^{-1}\)) \\ \hline Control & \(28.5\pm 1.4\) & \(27.2\pm 1.9\) & \(18.4\pm 4.1\) & \(1.8\pm 0.4\) & \(554.5\times 10^{-3}\pm 6.5\times 10^{-3}\) & \(82.0\times 10^{-3}\pm 1.6\times 10^{-3}\) \\ \hline  & & & & 2 IU/mL heparin with: & & \\ \hline
0.5 IU/mL & & & & & & \\ \hline
10 IU/mL & & & & & & \\ \hline  & & & & & & \\ \hline  & & & & & & \\ \hline
3.0 IU/mL & & & & & & \\ \hline  & & & & & & \\ \hline  & & & & & & \\ \hline \hline  & & & & & & \\ \hline \end{tabular}
\end{table} 
Table 4: Summary of the clotting time (CT), elastic (G\({}^{\prime}\)) and viscous (G\({}^{\prime\prime}\)) shear moduli at 300 s and linear slopes (m (G\({}^{\prime}\)) and m (G\({}^{\prime\prime}\))). Citrated blood was heparinised (2.0 IU/mL) and antagonised with various concentrations of protamine (0.5-3.0 IU/mL) before activation with Thromborel (\(n=3\)). Citrated blood without heparin activated by Thromborel served as control. more sensitive than those of the ball coagulometer.