Internal lysis of contracted clots is accelerated by fiber alignment and bundling
6 affiliations
- 1Rutgers University, Department of Biomedical Engineering
- 2University of Pennsylvania, Department of Cell and Developmental Biology
- 3Rutgers University, Department of Chemical and Biochemical Engineering
- 4East Carolina University, Department of Physics
- 5University of Massachusetts Lowell, Department of Chemistry
- 6University of Central Oklahoma, Department of Mathematics and Statistics
Abstract
BACKGROUND: Clot contraction is the volume shrinkage of a blood clot due to action of platelet-driven contractile forces. Clot contraction is known to accelerate internal fibrinolysis (the physiological degradation of the fibrin network) but restrict external fibrinolysis (the exogenous delivery of thrombolytic agents) in whole blood. We previously showed that external fibrinolysis is limited in contracted clots due to the densified fibrin network in the periphery, but the mechanism of acceleration of internal lysis is unknown. OBJECTIVES: We aimed to identify the driving mechanism that accelerated internal lysis of contracted clots. METHODS: A comprehensive array of wet-lab experiments at the micro- and macroscopic levels, as well as computational modeling, were used to systematically disentangle the dominating mechanism leading to faster fibrinolysis of contracted clots during internal fibrinolysis. Scanning electron microscopy and confocal microscopy were used to visualize clots made with platelet-rich plasma and platelet-poor plasma to study the fibrin network structure. Platelet-driven tension was mimicked by applying uniaxial tensile strain in both large clots and individual fibers. RESULTS: Clot contraction results in fibrin network structural changes-notably, a dense periphery and heterogeneous core. Internal lysis of clots made with platelet-rich plasma that contract normally was faster than all other clots tested. Tension delays lysis of individual fibers but accelerates lysis when fibers bundle with a high percent strain. CONCLUSION: Apparent thickening of fibers due to fibrin bundling as a result of platelet-driven fibrin rearrangement and alignment, rather than platelet-driven tension on fibers, drives the acceleration of internal fibrinolysis of contracted clots.
Related
- Effects of Fibrinogen and Thrombin Concentrations on Clot Structure and Internal Clot Lysis Time
- Association between knowledge, attitude, and practice regarding family doctor contract services and perceived healthcare barriers among contracted residents: a cross-sectional study in Shanghai, China
- Structural basis for inhibition of the lipid flippase MurJ by phage lysis protein SglPP7 suggests convergent evolution with other Sgl peptides
- Cancer-associated stroke: a comparative analysis of thrombus composition, resistance to lysis, and plasma biomarkers
- Personalized Prediction of Venetoclax-Associated Tumor Lysis Syndrome in Acute Myeloid Leukemia Using Drug Exposure, Genetic Polymorphisms, and Clinical-Laboratory Characteristics.
BibTeX
@article{risman2026internal,
title = {{Internal lysis of contracted clots is accelerated by fiber alignment and bundling}},
author = {Rebecca A. Risman and Eva Iungbliudt and Joshua Packard and Igor Novikov and Mason Lee Verhaeghe and John W. Weisel and Brittany E. Bannish and Valeri Barsegov and Nathan E. Hudson and Valerie Tutwiler},
journal = {Journal of thrombosis and haemostasis : JTH},
year = {2026},
month = jul,
doi = {10.1016/j.jtha.2026.07.007},
url = {https://doi.org/10.1016/j.jtha.2026.07.007},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Internal lysis of contracted clots is accelerated by fiber alignment and bundling
AU - Rebecca A. Risman
AU - Eva Iungbliudt
AU - Joshua Packard
AU - Igor Novikov
AU - Mason Lee Verhaeghe
AU - John W. Weisel
AU - Brittany E. Bannish
AU - Valeri Barsegov
AU - Nathan E. Hudson
AU - Valerie Tutwiler
PY - 2026
DA - 2026/07/18
JO - Journal of thrombosis and haemostasis : JTH
DO - 10.1016/j.jtha.2026.07.007
UR - https://doi.org/10.1016/j.jtha.2026.07.007
AB - BACKGROUND: Clot contraction is the volume shrinkage of a blood clot due to action of platelet-driven contractile forces. Clot contraction is known to accelerate internal fibrinolysis (the physiological degradation of the fibrin network) but restrict external fibrinolysis (the exogenous delivery of thrombolytic agents) in whole blood. We previously showed that external fibrinolysis is limited in contracted clots due to the densified fibrin network in the periphery, but the mechanism of acceleration of internal lysis is unknown. OBJECTIVES: We aimed to identify the driving mechanism that accelerated internal lysis of contracted clots. METHODS: A comprehensive array of wet-lab experiments at the micro- and macroscopic levels, as well as computational modeling, were used to systematically disentangle the dominating mechanism leading to faster fibrinolysis of contracted clots during internal fibrinolysis. Scanning electron microscopy and confocal microscopy were used to visualize clots made with platelet-rich plasma and platelet-poor plasma to study the fibrin network structure. Platelet-driven tension was mimicked by applying uniaxial tensile strain in both large clots and individual fibers. RESULTS: Clot contraction results in fibrin network structural changes-notably, a dense periphery and heterogeneous core. Internal lysis of clots made with platelet-rich plasma that contract normally was faster than all other clots tested. Tension delays lysis of individual fibers but accelerates lysis when fibers bundle with a high percent strain. CONCLUSION: Apparent thickening of fibers due to fibrin bundling as a result of platelet-driven fibrin rearrangement and alignment, rather than platelet-driven tension on fibers, drives the acceleration of internal fibrinolysis of contracted clots.
SN - 1538-7933
SN - 1538-7836
ER -