A Novel In-Vitro Platform to Answer How, When, and Why Clots Embolize

Abstract

Purpose: Blood clots that form intra-vascularly can break off, or embolize, and occlude a distal site, leading to deadly sequelae such as strokes and pulmonary embolisms. Embolization is a highly mechanical phenomenon during which hemodynamic forces overcome a clot's resistance to wall delamination or bulk fracture. While we and others have characterized these resistances, no prior work has experimentally demonstrated their role in actually promoting embolization. Thus, our objective was to build an in vitro platform to study how, when, and why clots embolize.

Methods: We designed a pulsatile flow loop in which clot mimics made from human blood are coagulated onto a porcine aortic substrate, creating a realistic clot/vascular interface. We prepared clots at 20%, whole blood, and 60% hematocrit from six female and six male donors and subjected them to a scaled physiological venous flow profile. We measured intra-cycle shear strain and cycles-to-embolization and used a Monte Carlo approach to correlate both with previously published clot stiffness and fracture toughness data.

Results: With increasing hematocrit (20%, whole blood, and 60%), intra-cycle shear strain increased from 0.276 ± 0.031 to 0.320 ± 0.037 and 0.426 ± 0.051, while cycles-to-embolization decreased from 13,206 ± 2,072 to 8,618 ± 1,570 and 4,253 ± 1,425, respectively. Neither sex nor clot height had a consistent effect. Furthermore, shear strain was negatively correlated with clot stiffness, while cycles-to-embolization were positively correlated with fracture toughness.

Conclusion: Our platform enables the experimental study of clot embolization. We show that increased hematocrit leads to larger clot deformation and faster embolization, likely by decreasing clot stiffness and toughness.