Abstract Number: PB0458
Meeting: ISTH 2020 Congress
Background: Blood clots or intravascular thrombi undergo volume shrinkage driven by activated platelets. Clot contraction results in the compression of red blood cells (RBCs) into polyhedral structures (polyhedrocytes) in the core of the clot, while most fibrin and platelets concentrate at the clot periphery.
Aims: Determine the physical mechanisms driving this segregation.
Methods: The redistribution of the components in contracting clots were quantified using histology and scanning electron microscopy. Coupling experimental data with an active mechanochemical model allowed us to analyze why this segregated distribution was more favorable than a homogenous distribution.
Results: Platelets exert tension on the fibrin network leading to pressure on and compression of the RBCs. RBC compression and densification of fibrin leads to stiffening of the overall clot. A stiffer clot yields more resistance to platelet contraction, upregulating mechanosensitive pathways in platelets that trigger the generation of larger contractile forces and decreased active potential. This results in a lower energy for the overall system coupled when compared to a hypothetical homogenous clot distribution, therefore revealing an active cell sorting mechanism drives the structural non-uniformity of contracting clots. The finding that contraction drives the structural segregation of clots due to minimization of active and passive energy provides a theoretical basis for this important biological phenomenon.
Conclusions: Structural remodeling of blood clots contributes to the course and outcomes of thrombosis as it changes the properties of intravital blood clots and thrombi, including their ability to block a vessel lumen as well as to withstand mechanical deformations, rupture, and enzymatic lysis.
To cite this abstract in AMA style:Tutwiler V, Chen X, Litvinov R, Khismatullin R, Weisel J, Shenoy V. Clot Contraction Drives Structural Redistribution of Platelets, Fibrin and Red Blood Cells through Active Cell Sorting [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/clot-contraction-drives-structural-redistribution-of-platelets-fibrin-and-red-blood-cells-through-active-cell-sorting/. Accessed October 1, 2023.
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