Fluid and Solute Transport in the Interstitial Space of Blood Clots

Abstract

Biological tissues can be described as porous media consisting of granular cells and a fibrous extracellular matrix. The transport of fluids and solutes through the interstitial space between cells regulates many physiological and pathological processes. In the case of blood clots, the ability of solutes to move into and out of the inner core of a clot dictates both growth and dissolution. Two physical properties that govern the rate of fluid and solute transport are the hydraulic permeability and diffusivity. Here, we report the experimental measurement of these two properties over a large range of clot compositions. Hydraulic permeability was calculated by measuring the interstitial fluid velocity through clots at a constant pressure gradient. The permeability changes by up to five orders-of-magnitude, spanning the range of 10 −5 -10 −1 μm 2 , depending on the absolute and relative volume fractions of-cells (platelets) and a fibrous protein (fibrin). The permeability of clots can be predicted using solutions to Stokes flow in disordered fibrous media in the low cell volume fraction limit and by the Brinkman equation for clots with moderate to high cell volume fractions. The diffusivity of macromolecule tracers was measured using fluorescence recovery after photobleaching (FRAP) in fibrin gels. Diffusion of macromolecules becomes hindered even at low fibrin volume fractions (<0.05). These data are the first measurements of permeability and diffusivity over the physiological range of blood clot compositions, and thus will allow for better modeling and predictions of clot growth. These findings have important implications in the development of drug delivery strategies for disrupting clot formation and enhancing clot dissolution. 457

Blood flow and mass transfer regulation of coagulation

“…Experimental measurements of fluid and solute transport in thrombi formed at a range of fibrin and platelet concentrations provide lookup tables of physical properties such as hydraulic permeability and diffusivity and insight into how these properties change with thrombus composition. 62,73 Thrombi elasticity is correlated to these transport properties, at least at low strains. 77 This link between measurements of clot mechanics through methods, such as ultrasound or thromboelastography, and interstitial transport, could guide therapeutic choices with respect to fibrinolytic agents and mechanical retrieval of thrombi.…”

“…72 Similar gap sizes were measured by focused ion bead-scanning electron microscopy of thrombi formed under flow in vitro. 73 …”