Contraction of blood clots and thrombi: pathogenic and clinical significance

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Abstract

This review is the frst systematic description of spontaneous blood clot shrinkage, aka clot retraction or contraction. The driver of this process is the contraction of the actin-myosin complex inside activated platelets. The platelet contractile force is transmitted via focal contacts to extracellular fbrin fbers, causing compaction of the three-dimensional fbrin network along with the embedded erythrocytes. The main structural consequences of clot contraction include redistribution of the fbrin-platelet meshwork toward the periphery of the clot and compression of erythrocytes in the core of the clot followed by their deformation into polyhedral cells called “polyhedrocytes”. These structural signatures of clot contraction in ex vivo thrombi and thrombotic emboli derived from various locations indicate that thrombi undergo intravital contraction within blood vessels in vivo. Pathogenic consequences of clot contraction may vary. Thus, contraction of a thrombus changes the vessel lumen, thereby modulating local blood flow in the thrombotic occlusion area. Thrombus shrinkage changes its porosity and permeability for fbrinolytic enzymes. The extent of thrombus compression and densifcation can determine the likelihood of its mechanical rupture, i. e. thrombotic embolization. Several clinical studies have revealed that clot contraction is suppressed in the blood of patients with (pro)thrombotic conditions, such as ischemic stroke, venous thrombosis, and systemic lupus erythematosus. This reduction of clot contraction is due to platelet dysfunction caused by their chronic hyperactivation and energetic exhaustion. Clot contraction depends significantly on cellular and protein composition of the blood; in particular, a high hematocrit and hyperfbrinogenemia both reduce clot contraction, while activated monocytes enhance clot contraction by expressing tissue factor and promoting thrombin generation. The degree of clot contraction abnormalities in thrombotic states generally correlates with disease severity, which confrms the pathogenic importance of clot contraction. In patients with pulmonary embolism clot contraction is decreased signifcantly compared to that in isolated venous thrombosis, indirectly suggesting that a less compacted thrombus is more prone to embolization. This observation points to a potential diagnostic and prognostic value of the clot contraction assay as a novel test for ongoing or threatening thromboembolism. Collectively, contraction of blood clots and thrombi is an underappreciated and understudied process that has a major pathogenic and clinical signifcance in (pro)thrombotic conditions of various etiologies.

About the authors

R. I. Litvinov

University of Pennsylvania School of Medicine;
Kazan (Volga region) Federal University

Email: fake@neicon.ru

Rustem I. Litvinov – MD, PhD, Professor, Senior Research Investigator, Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine; Adjunct Professor, Department of Biochemistry and Biotechnology, Institute of Fundamental Medicine and Biology; Chief Researcher, Head of the Laboratory “Protein-Cell Interactions”, Kazan (Volga region) Federal University

421 Curie Blvd., Philadelphia, Pennsylvania, 19104, 

18 Kremlevskaya ul., Kazan, 420008

United States

A. D. Peshkova

Kazan (Volga region) Federal University

Author for correspondence.
Email: alinapeshkova@list.ru

Alina D. Peshkova – Postgraduate Student, Department of Biochemistry and Biotechnology, Institute of Fundamental Medicine and Biology; Junior Research Fellow, Laboratory “Protein-Cell Interactions”

18 Kremlevskaya ul., Kazan, 420008

Russian Federation

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Copyright (c) 2018 Litvinov R.I., Peshkova A.D.

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