Phase transitions during compression and decompression of clots from platelet-poor plasma, platelet-rich plasma and whole blood.

Unlabelled: Blood clots are required to stem bleeding and are subject to a variety of stresses, but they can also block blood vessels and cause heart attacks and ischemic strokes. We measured the compressive response of human platelet-poor plasma (PPP) clots, platelet-rich plasma (PRP) clots and whole blood clots and correlated these measurements with confocal and scanning electron microscopy to track changes in clot structure. Stress-strain curves revealed four characteristic regions, for compression-decompression: (1) linear elastic region; (2) upper plateau or softening region; (3) non-linear elastic region or re-stretching of the network; (4) lower plateau in which dissociation of some newly made connections occurs. Our experiments revealed that compression proceeds by the passage of a phase boundary through the clot separating rarefied and densified phases. This observation motivates a model of fibrin mechanics based on the continuum theory of phase transitions, which accounts for the pre-stress caused by platelets, the adhesion of fibrin fibers in the densified phase, the compression of red blood cells (RBCs), and the pumping of liquids through the clot during compression/decompression. Our experiments and theory provide insights into the mechanical behavior of blood clots that could have implications clinically and in the design of fibrin-based biomaterials.

Statement Of Significance: The objective of this paper is to measure and mathematically model the compression behavior of various human blood clots. We show by a combination of confocal and scanning electron microscopy that compression proceeds by the passage of a front through the sample that separates a densified region of the clot from a rarefied region, and that the compression/decompression response is reversible with hysteresis. These observations form the basis of a model for the compression response of clots based on the continuum theory of phase transitions. Our studies may reveal how clot rheology under large compression in vivo due to muscle contraction, platelet retraction and hydrodynamic flow varies under various pathophysiological conditions and could inform the design of fibrin based biomaterials.