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Blood clot contraction differentially modulates internal and external fibrinolysis
Author(s): ,
Valerie Tutwiler
Affiliations:
Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
,
Alina D. Peshkova
Affiliations:
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation
,
Giang Le Minh
Affiliations:
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation
,
Sergei Zaitsev
Affiliations:
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
,
Rustem I. Litvinov
Affiliations:
Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA. Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation
,
Douglas B. Cines
Affiliations:
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
John W. Weisel
Affiliations:
Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
Correspondence: John W. Weisel, Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, 421 Curie Blvd, BRB II/III, Room 1154, Philadelphia, PA 19104‐6058, USA|Tel.: +1 215 898 3573|E‐mail: weisel@pennmedicine.upe
ISTH Academy. W. Weisel J.
Feb 8, 2019; 273386
John W. Weisel
John  W. Weisel
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Background
Fibrinolysis involves dissolution of polymeric fibrin networks that is required to restore blood flow through vessels obstructed by thrombi. The efficiency of lysis depends in part on the susceptibility of fibrin to enzymatic digestion, which is governed by the structure and spatial organization of fibrin fibers. How platelet‐driven clot contraction affects the efficacy of fibrinolysis has received relatively little study.
Objective
Here, we examined the effects of clot contraction on the rate of internal fibrinolysis emanating from within the clot to simulate (patho)physiological conditions and external fibrinolysis initiated from the clot exterior to simulate therapeutic thrombolysis.
Methods
Clot contraction was prevented by inhibiting platelet myosin IIa activity, actin polymerization or platelet‐fibrin(ogen) binding. Internal fibrinolysis was measured by optical tracking of clot size. External fibrinolysis was determined by the release of radioactive fibrin degradation products.
Results and Conclusions
Clot contraction enhanced the rate of internal fibrinolysis ∼2‐fold. In contrast, external fibrinolysis was ~4‐fold slower in contracted clots. This dichotomy in the susceptibility of contracted and uncontracted clots to internal vs. external lysis suggests that the rate of lysis is dependent upon the interplay between accessibility of fibrin fibers to fibrinolytic agents, including clot permeability, and the spatial proximity of the fibrin fibers that modulate the effects of the fibrinolytic enzymes. Understanding how compaction of blood clots influences clot lysis might have important implications for prevention and treatment of thrombotic disorders.
Keyword(s)
blood clotting, clot retraction, fibrin, fibrinolysis, platelets
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