In this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices.

A reliable in vitro dynamic test method to evaluate device thrombogenicity is very important for the improvement of the design and safety of blood-contacting medical devices, while reducing the use of animal studies. In this study, a recirculating flow loop system was developed for thrombogenicity testing, using donor sheep blood anticoagulated with Anticoagulant Citrate Dextrose Solution A (ACDA) and used within 24–36 hr postdraw. Immediately before testing, the blood was recalcified and heparinized to a donor-specific target concentration. The heparinization level was based on a static pretest, in which latex tubes were incubated at room temperature for 30 min in blood with a series of heparin concentrations and evaluated for thrombus deposition. For dynamic testing, blood was recirculated at room temperature through a polyvinyl chloride (PVC) tubing loop containing a test material for 1 hr at 200 ml/min using a roller pump. Nine materials were investigated: a negative control (polytetrafluoroethylene [PTFE]), a positive control (latex), and seven commonly used biomaterials including PVC, two silicones with different formulations (Q-Sil and V-Sil), nylon, polyurethane (PU), high-density polyethylene (HDPE), and polyether block amide (PEBAX). The results showed that latex was significantly more thrombogenic than all the other materials (p < 0.05), PVC and Q-Sil exhibited intermediate thrombogenicity with significantly more thrombus surface coverage and thrombus weight than PTFE (p < 0.05), whereas PTFE and the rest of the biomaterials had little to no thrombus deposition. In summary, the test loop system was able to effectively differentiate materials with different thrombogenic potentials.