Prediction of Thrombus Formation in Ladder Network and Stability of Thrombus in a Bifurcation

Thrombus formation on complex branched networks like extracorporeal membrane oxygenators (ECMO) is poorly understood. In this work, we built a COMSOL model on branched networks, to understand and predict the thrombus formation under blood flow. A microfluidic ladder network design was used to study the change in hemodynamics. The microfluidic ladder sizes are chosen to mimic the physiologically relevant shear rates of 300 s--1 and 700 s--1 in main channels and bypasses respectively. The COMSOL model results were analyzed to understand the flow dynamics inside the ladder network. We predicted the thrombus nucleation points in the ladder network, based on shear grad ients, velocity profile, thrombin transport and platelet concentration. Thrombi were modeled as 2D spheres in the predicted locations of the ladder network. Thrombus growth was modeled in six cases to account for the progressive growth of thrombi the ladder network. Shear rates, thrombin transport rate and platelet percentage were estimated for each case of simulation from COMSOL to develop a set of metrics for thrombus prediction. The predictions from the model were then validated using experimental data from a similar microfluidic ladder device. Experiments were done using recalcified whole human blood pumped into the device at a constant inlet flow rate of 2 microL min--1 . Observations from the experiment revealed that clots are formed at the intersection of bypasses with main channels and not all clots were occlusive. The formation of thrombus followed a pattern progressing from n th bypass to (n+1)th bypass. The geometry induced effects on thrombus formation patterns proved the hypothesis that geometry plays a vital role in spatio-temporal aspects of thrombus nucleation and growth. Images recorded in the experiments of ladder network revealed that not all thrombi in the ladder network went to complete occlusion. Hydrodynamic forces were found to control the occlusion scenario of the thrombus. Threshold of occlusion was studied in a thrombus growing in a straight channel and the results were extended to bifurcations---blood vessels branching into two smaller vessels. Our study revealed that bifurcation ratio and the occlusion of thrombus in a bifurcation are related to each other. Mathematical model developed to understand the critical bifurcation ratios can be used to study the interaction of multiple clots in a geometry from stability perspective. An integrated model that predicts thrombus nucleation and stability in a given geometry holds potential in development of therapeutic and diagnostic devices for blood disorders