Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms

2020/03/18 by John M. Nicklas, Aviva Gordon, Peter K. Henke · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Venous Thromboembolism Diagnosis and Management #Inflammasome and immune disorders #Neutrophil, Myeloperoxidase and Oxidative Mechanisms #Thrombus #Neutrophil extracellular traps #Medicine #Thrombosis #Immune system #Venous thrombosis #Inflammation #Fibrinolysis #Pulmonary embolism #Context (archaeology) #Immunology #Pathology #Biology #Internal medicine

paper · pdf · doi:10.3390/ijms21062080

openalex publication_date 2020/03/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of treatment. Herein, we review the current literature, including the molecular mechanisms of fibrinolysis and collagenolysis, as well as the critical cellular roles of macrophages, neutrophils, and endothelial cells. We propose two general models for the operation of the immune system in the context of venous thrombosis. In early thrombus resolution, neutrophil influx stabilizes the tissue through NETosis. Meanwhile, macrophages and intact neutrophils recognize the extracellular DNA by the TLR9 receptor and induce fibrosis, a complimentary stabilization method. At later stages of resolution, pro-inflammatory macrophages police the thrombus for pathogens, a role supported by both T-cells and mast cells. Once they verify sterility, these macrophages transform into their pro-resolving phenotype. Endothelial cells both coat the stabilized thrombus, a necessary early step, and can undergo an endothelial-mesenchymal transition, which impedes DVT resolution. Several of these interactions hold promise for future therapy.

Citations

• Leukocytes and the Natural History of Deep Vein Thrombosis
• The Epidemiology of Chronic Venous Insufficiency and Varicose Veins
• Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization
• Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites
• Of Mice and Not Men: Differences between Mouse and Human Immunology
• The role of leukocytes in thrombosis
• Current incidence of venous thromboembolism and comparison with 1998: a community-based study in Western France
• Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function
• Neutrophil extracellular traps in immunity and disease
• Genetically engineered pigs as models for human disease
• The Role of Inflammation in Venous Thromboembolism
• Neutrophil Extracellular Traps in Arterial and Venous Thrombosis
• Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases

Cited by

• Deep vein thrombosis [wikipedia]

Related

• Fibrinolysis and Inflammation in Venous Thrombus Resolution
• Leukocytes and the Natural History of Deep Vein Thrombosis
• Venous Thrombosis and Post-Thrombotic Syndrome: From Novel Biomarkers to Biology
• Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization
• The coming of age of neutrophil extracellular traps in thrombosis: Where are we now and where are we headed?