Micromechanical Force Measurement of Clotted Blood Particle Cohesion: Understanding Thromboembolic Aggregation Mechanisms

Abstract

Purpose Arterial shear forces may promote the embolization of clotted blood from the surface of thrombi, displacing particles that may occlude vasculature, with increased risk of physiological complications and mortality. Thromboemboli may also collide in vivo to form metastable aggregates that increase vessel occlusion likelihood. Methods A micromechanical force (MMF) apparatus was modified for aqueous applications to study clot-liquid interfacial phenomena between clotted porcine blood particles suspended in modified continuous phases. The MMF measurement is based on visual observation of particle-particle separation, where Hooke’s Law is applied to calculate separation force. This technique has previously been deployed to study solid–fluid interfacial phenomena in oil and gas pipelines, providing fundamental insight to cohesive and adhesive properties between solids in multiphase flow systems. Results This manuscript introduces distributed inter-particle separation force properties as a function of governing physio-chemical parameters; pre-load (contact) force, contact time, and bulk phase chemical modification. In each experimental campaign, the hysteresis and distributed force properties were analysed, to derive insight as to the governing mechanism of cohesion between particles. Porcine serum, porcine albumin and pharmaceutical agents (alteplase, tranexamic acid and hydrolysed aspirin) reduced the measurement by an order of magnitude from the baseline measurement—the apparatus provides a platform to study how surface-active chemistries impact the solid–fluid interface. Conclusion These results provide new insight to potential mechanisms of macroscopic thromboembolic aggregation via particles cohering in the vascular system—data that can be directly applied to computational simulations to predict particle fate, better informing the mechanistic developments of embolic occlusion.

CFD-DEM model of plugging in flow with cohesive particles

“…The cohesive energy is calculated in the JKR limit from the micromechanical force measurements reported by Yang et al 21 . We note that these values of cohesion energy are about 3-orders greater than the cohesion of clotted blood particles 28 .…”

CFD-DEM model of plugging in flow with cohesive particles

“…In the interpolation, we used data points obtained in the interval -4.2...-1.75 0 C where γ ice ∼25...174 mJ/m 2 . We note that these values of cohesion energy are about 3-orders greater than the cohesion of clotted blood particles 29 .…”