Model predictions of deformation, embolization and permeability of partially obstructive blood clots under variable shear flow

Abstract

Thromboembolism, one of the leading causes of morbidity and mortality worldwide, is characterized by formation of obstructive intravascular clots (thrombi) and their mechanical breakage (embolization). A novel two-dimensional multi-phase computational model is introduced that describes active interactions between the main components of the clot, including platelets and fibrin, to study the impact of various physiologically relevant blood shear flow conditions on deformation and embolization of a partially obstructive clot with variable permeability. Simulations provide new insights into mechanisms underlying clot stability and embolization that cannot be studied experimentally at this time. In particular, model simulations, calibrated using experimental intravital imaging of an established arteriolar clot, show that flow-induced changes in size, shape and internal structure of the clot are largely determined by two shear-dependent mechanisms: reversible attachment of platelets to the exterior of the clot and removal of large clot pieces. Model simulations predict that blood clots with higher permeability are more prone to embolization with enhanced disintegration under increasing shear rate. In contrast, less permeable clots are more resistant to rupture due to shear rate-dependent clot stiffening originating from enhanced platelet adhesion and aggregation. These results can be used in future to predict risk of thromboembolism based on the data about composition, permeability and deformability of a clot under specific local haemodynamic conditions.

In vivo measurement of blood clot mechanics from computational fluid dynamics based on intravital microscopy images

“…Expectedly, our stress results compare well with both the 2D in vivo stress calculations (see Figure 4 in Ref. [45]) and, the 40 dyn/cm 2 in vitro value for "dynamic" elastic modulus of less activated platelet aggregate (see Table 1 in [33]).…”

Plasma fibrin clot structure and thromboembolism: clinical implications

“…61 Recently published computational model simulations describing interactions between main clot components under shear flow suggest that blood clots with higher clot shell permeability are more prone to embolization under increasing shear rate. 62 It has been reported that some environmental factors affect fibrin clot structure in patients with DVT. Long -term exposure to particulate matter with a diameter of less than 10 μm (PM 10 ) has been associated with a denser fibrin network with K s decreased by 22% in 103 patients with DVT but not in controls, suggesting an increased risk of recurrent episodes in patients predisposed to venous thrombosis.…”

In Silico Hemostasis Modeling and Prediction

“…Using the continuous viscoelastic model of the preformed heterogeneous clots, it was recently shown that the stability of such thrombi against the flow is largely dependent on the internal permeability distribution. 41 Another continuous model of thrombus formation which takes into account platelet aggregation, secretion, and coagulation has been used to study the dynamics of thrombus formation on the tissue factor (TF) observed in vitro under venous shear rates. This model predicted the dependence of both clot size and internal composition on the surface density of the TF and the length of the corresponding region.…”