"What makes blood clots break off?" A Back-of-the-Envelope Computation Toward Explaining Clot Embolization.

Abstract

One in four deaths worldwide is due to thromboembolic disease; that is, one in four people die from blood clots first forming and then breaking off or embolizing. Once broken off, clots travel downstream, where they occlude vital blood vessels such as those of the brain, heart, or lungs, leading to strokes, heart attacks, or pulmonary embolisms, respectively. Despite clots' obvious importance, much remains to be understood about clotting and clot embolization. In our work, we take a first step toward untangling the mystery behind clot embolization and try to answer the simple question: "What makes blood clots break off?" To this end, we conducted experimentally-informed, back-of-the-envelope computations combining fracture mechanics and phase-field modeling. We also focused on deep venous clots as our model problem. Here, we show that of the three general forces that act on venous blood clots-shear stress, blood pressure, and wall stretch-induced interfacial forces-the latter may be a critical embolization force in occlusive and non-occlusive clots, while blood pressure appears to play a determinant role only for occlusive clots. Contrary to intuition and prior reports, shear stress, even when severely elevated, appears unlikely to cause embolization. This first approach to understanding the source of blood clot bulk fracture may be a critical starting point for understanding blood clot embolization. We hope to inspire future work that will build on ours and overcome the limitations of theseback-of-the-envelope computations.