Abstract Number: OC 11.3
Meeting: ISTH 2021 Congress
Background: Blood clot contraction or the volume shrinkage of the clot plays a critical role in the restoration of blood flow past otherwise obstructive thrombi. Contraction is driven by platelet generation forces and results in the compression of red blood cells (RBCs) into a tessellated network in the core of the clot, leading to the terminology of polyhedrocytes.
Aims: The aim of this work was to determine the mechanism driving the redistribution of the clot.
Methods: Histology and scanning electron microscopy were utilized to characterize the ultrastructure of contracting blood clots and coupled with a poroelastic computation model.
Results: Through the use of microscopy we determined that clot contraction results in
1) redistribution of platelets/fibrin to the exterior of the blood clot,
2)densification of fibrin in the exterior region, and
3) packing RBCs into the core of the clot in a time dependent manner.
To reveal the physical mechanisms driving this segregation, a mechano-chemical model that relates the feedback between platelet contractility and the dynamic stiffness of the clot was developed. Our model predicts that as resistance to contraction of platelets increases, their mechanosensitive pathways are upregulated and the active free energy decreases. Redistribution lowers the system’s free energy. This mechanism of increasing contractility in response to substrate stiffness provides a basis for the kinetics of segregation as a function of clot composition and platelet contraction.
Conclusions: This has important clinical implications as patients with thrombotic conditions such as ischemic strokes and venous thromboembolism have impaired clot contraction compared to healthy subjects, pointing to a potential role of contraction in the pathogenesis of thrombosis. The finding that contraction drives the structural redistribution of clots observed here provides a potential basis for the decrease in efficacy of thrombolytic treatment with increasing time following symptom onset and has implications for the development of novel thrombolytics.
To cite this abstract in AMA style:Tutwiler V, Chen X, Litvinov RI, Khismatullin R, Kaufmanova J, Nagaswami C, Weisel JW, Shenoy VB. Active Sorting of Platelets and Red Blood Cells in Contracting Blood Clots is Driven by Platelet-generated Forces that Stiffen Fibrin [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/active-sorting-of-platelets-and-red-blood-cells-in-contracting-blood-clots-is-driven-by-platelet-generated-forces-that-stiffen-fibrin/. Accessed February 27, 2024.
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