Manuscript handled by: P. H. Reitsma
Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development
Version of Record online: 10 JUN 2014
© 2014 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 12, Issue 6, pages 860–870, June 2014
How to Cite
Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development. J Thromb Haemost 2014; 12: 860–70., , , , , , , , , .
Final decision: P. H. Reitsma, 21 March 2014
- Issue online: 10 JUN 2014
- Version of Record online: 10 JUN 2014
- Accepted manuscript online: 27 MAR 2014 05:55AM EST
- Manuscript Accepted: 21 MAR 2014
- Manuscript Received: 15 JAN 2014
- National Heart, Lung, and Blood Institute of the National Institutes of Health. Grant Number: R01HL102101
- blood platelets;
- clinical pathology;
- venous thromboembolism
A growing health problem, venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), requires refined diagnostic and therapeutic approaches. Neutrophils contribute to thrombus initiation and development in experimental DVT. Recent animal studies recognized neutrophil extracellular traps (NETs) as an important scaffold supporting thrombus stability. However, the hypothesis that human venous thrombi involve NETs has not undergone rigorous testing.
To explore the cellular composition and the presence of NETs within human venous thrombi at different stages of development.
Patients and Methods
We examined 16 thrombi obtained from 11 patients during surgery or at autopsy using histomorphological, immunohistochemical and immunofluorescence analyses.
We classified thrombus regions as unorganized, organizing and organized according to their morphological characteristics. We then evaluated them, focusing on neutrophil and platelet deposition as well as micro-vascularization of the thrombus body. We observed evidence of NET accumulation, including the presence of citrullinated histone H3 (H3Cit)-positive cells. NETs, defined as extracellular diffuse H3Cit areas associated with myeloperoxidase and DNA, localized predominantly during the phase of organization in human venous thrombi.
NETs are present in organizing thrombi in patients with VTE. They are associated with thrombus maturation in humans. Dissolution of NETs might thus facilitate thrombolysis. This finding provides new insights into the clinical development and pathology of thrombosis and provides new perspectives for therapeutic advances.