# Dynamic and Quantitative Assessment of Blood Coagulation Status with an Oscillatory Rheometer
## 1 Introduction  
Annually, almost one million procedures in heart surgery are performed worldwide using a heart-lung machine [1]. The extracorporeal circulation (ECC) comprises several methods such as extracorporeal membrane oxygenation (ECMO) to provide respiratory support, extracorporeal life support (ECLS) and ventricular assist devices (VAD) to give cardiac support and dialysis [2,3]. Anticoagulants (e.g., heparin) are necessary to prevent life-threatening coagulation induced by the contact of blood with foreign surfaces [4]. To prevent bleeding or thrombosis during and after ECC, which can last several hours, a continuous monitoring of the coagulation status is necessary [5]. Currently, the modern intensive care does not provide a comprehensive point-of-care solution for the coagulation status and blood clotting problems, because a single medical device that fast and reliably detects all bleeding-based disorders (coagulation, fibrinolysis and platelet function) is lacking so far [2]. Thus, a haemostasis system that is able to perform fast and complex analyses with low or no sample preparation near the patient (point-of-care) is required. Currently, there are many physical approaches to realise such a haemostasis system, but none can be used as a point-of care system so far. For example a nanomechanic device filled with hydrogels to measure single platelets within a microfluidic channel was suggested as additional platelet function assay [6], but measurement of coagulation dynamics would not be possible. The acoustic radiation force orthogonal excitation optical coherence elastography (ARFOE-OCE) as a non-contact measurement of coagulation in whole blood is advantageous being non-invasive, however, can only determine the elastic shear modulus so far [7]. A laser illumination of the blood sample is detected by a high speed complementary-metal-oxide-semiconductor (CMOS) camera in the Laser Speckle Rheology (LSR) method. A close correlation to conventional coagulation results was recorded by the researchers, still needing further improvements for a miniaturisation towards a hand-held LSR system [8; 9]. We intend to address the point-of-care issue by rheometry, which can provide important information about the microstructure and dynamics of complex fluids such as polymer solutions and suspensions of colloid particles. Similar to those technical solutions, human whole blood is a complex suspension of various cell types and proteins that is subject to continuous variations. Mathematical models have shown a correlation between haematocrit and haemodynamic factors. Due to its diverse and changing states human whole blood can be regarded as a Newtonian as well as a non-Newtonian fluid [10; 11]. Monitoring the changes in viscoelastic properties of blood clotting provides a real-time indicator of the blood coagulation status of a patient. The conversion of fibrinogen into insoluble fibrin through the enzyme thrombin is an important step in the coagulation process [12]. Afterwards, following the coagulation cascade, fibrin is cross-linked with aggregated platelets leading to a platelet-fibrin mesh. This increases the viscoelastic modulus of coagulated blood [13]. The clotting time (CT) can be obtained by measuring changes of viscoelastic properties of human whole blood, which is an important indicator of the patient's coagulation status. During the coagulation process the viscoelastic modulus increases over time and the linear slope describes the dynamics of clot formation. The maximum plateau modulus provides information on clot firmness, which is dependent on blood fibrinogen level, fibrin cross-linking and platelet numbers [8]. In the long run, we intend to develop a small and relatively economical rheometer to be used in clinical diagnostics or even in a point-of-care setting. Here, the first step was to investigate if an already commercially used rheometer can detect the coagulation process and differentiate various coagulation assays.