Quartz crystal microbalance (QCM) is widely used for the investigation of human blood mechanical properties, and shows high sensitivity for monitoring select dynamic processes, including red blood cell sedimentation and aggregation, coagulation, plasma protein absorption, as well as evaluating the bio-compatibility/affinity of different materials, etc. The present study provides a critical analysis of the challenges associated with data modelling and data interpretation, with respect to a QCM-based experimental setup. Here, the modelling approach selected for use is based on the analysis of the interactions that occur between an oscillating QCM surface and different blood components adhering to the surface. The resultant mathematical model overcomes these challenges by presenting simple, interpretable output parameters for monitoring experimental erythrocyte sedimentation in whole blood (WB), platelet aggregation in platelet rich plasma (PRP) and fibrin polymerisation in platelet poor plasma (PPP).