OC 24.2 - Heterogeneous Growth of Platelet Thrombi

Background: Arterial thrombi are complex blood clots that rapidly occlude arteries and cause ischemic events such as heart attacks and strokes. Unlike homogeneous coagulation clots, arterial thrombi have a unique heterogeneous architecture created by the aggregation of platelets and von Willebrand Factor. This unique architecture has been observed in scales ranging from microfluidic assays to clots retrieved from patients following an ischemic event. Current cellular-scale aggregation models or continuum computational models produce this unusual large-scale architecture.

Aims: Aim 1 is to identify the growth of heterogeneous clot structures in multiple experimental models. Aim 2 is to model heterogeneous growth using a probabilistic, agent-based model.

Methods: The structure of thrombi growing in capillary tubes was quantified using 2D brightfield images and 3D microcomputed tomography. An agent-based model was generated in NetLogo with the transitions in platelet behavior described by probabilities of four simple phenomena: 1) platelet margination, 2) platelet rolling, 3) stable platelet capture and 4) stochastic embolization of platelets.

Results: Experimentally, high shear-induced platelet thrombi grow as distinct, periodic structures that merge into a single solid. This periodic architecture was also identified in thrombi retrieved from patients by thrombectomy. (Figure 1) Model parameters were fit based on experimental data using computer vision to determine what combination of values mimic structures seen experimentally. Our parsimonious model of platelet movement was sufficient to re-create the heterogeneous growth and architecture observed in vitro and in vivo and accurately predict responses to perturbations in the initial conditions. (Figure 2)

Conclusion(s): This work reveals the periodic heterogeneous structure of arterial thrombi and demonstrates how this structure is an emergent phenomenon from four simple actions. These insights help explain how arterial thrombi develop from single platelets to complex whole clots.