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Recent Insights into the Molecular and Cellular Contributions to Venous Thrombosis

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Molecular and Translational Vascular Medicine

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

Deep vein thrombosis (DVT) and pulmonary embolism are common mortal/morbid diseases worldwide, and improvements in prophylaxis and therapy have been elusive. The basic pathophysiology of how a thrombus forms in vivo and how it resolves are now better understood through experiments with animal models. Inflammation can both cause and incite venous thrombosis. Leukocytes, platelets, and coagulation factors coalesce locally after a thrombogenic stimulus occurs. Cell adhesion molecules, such as P-selectin, bridge the interface of thrombosis and inflammation, and are both biomarkers for, and pathogenic in DVT. Once DVT forms, natural thrombolysis occurs primarily via the urokinase-type plasminogen activator (uPA)–plasmin system. Alternative pathways also exist for venous thrombus resolution, including the matrix metalloproteinases. A new concept in DVT resolution related to sterile inflammation is clearance of procoagulant necrotic leukocytes and platelets, in part mediated by TLR9 signaling. A consequence of DVT is the proximate vein wall injury, which is dependent on the mechanism and duration of the thrombus-vein wall contact. Both vascular smooth muscle cells and endothelial cells maintain normal vein homeostasis, but adopt an injury response after thrombosis that may lead to vein fibrosis. In humans, multiple biomarkers are now available, but increased specificity for venous thrombosis is still elusive. Some of these biomarkers such as P-selectin may also play a causative role, and be attractive therapeutic targets for nonanticoagulant DVT prophylaxis and treatment.

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Authors and Affiliations

  1. Department of Surgery, Section of Vascular Surgery, University of Michigan, 1500 East Medical Center Drive, CVC5463, Ann Arbor, MI, 48109, USA

    Peter K. Henke MD, Jose A. Diaz MD, Daniel D. Myers Jr. DVM, MPH, DACLAM & Thomas W. Wakefield MD

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  1. Peter K. Henke MD
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  2. Jose A. Diaz MD
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  3. Daniel D. Myers Jr. DVM, MPH, DACLAM
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  4. Thomas W. Wakefield MD
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Correspondence to Peter K. Henke MD .

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Editors and Affiliations

  1. , The University of North Carolina, McAllister Heart Institute, 101 Manning Drive, Chapel Hill, 27599-7525, USA

    Jonathon W. Homeister

  2. , The University of North Carolina, McAllister Heart Institute, 103 Mason Farm Road, Chapel Hill, 27599-7525, USA

    Monte S. Willis

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Henke, P.K., Diaz, J.A., Myers, D.D., Wakefield, T.W. (2012). Recent Insights into the Molecular and Cellular Contributions to Venous Thrombosis. In: Homeister, J., Willis, M. (eds) Molecular and Translational Vascular Medicine. Molecular and Translational Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-906-8_3

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