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48 - Role of Platelets and Thrombin in Metastasis
- from PART II - CLINICAL RESEARCH
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- By Boris Kobrinsky, New York University School of Medicine, United States, Simon Karpatkin, New York University School of Medicine, United States, David L. Green, New York University School of Medicine, United States
- Edited by David Lyden, Danny R. Welch, Bethan Psaila
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- Book:
- Cancer Metastasis
- Published online:
- 05 June 2012
- Print publication:
- 25 April 2011, pp 552-562
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- Chapter
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Summary
In response to vascular injury, platelets become adherent and undergo activation and aggregation. The formation of the primary hemostatic platelet plug occurs simultaneously with surface activation of coagulation, leading to thrombin generation and fibrin formation. Platelet function also contributes to thrombus formation in pathologic settings, leading to vascular occlusion, usually in the setting of underlying vascular disease. Platelets contain many biologically active mediators that are released upon activation, including growth factors, coagulation factors, adhesive ligands, proteases, heparanase, cytokines, chemokines, and vasoactive lipids. Other functions of platelets include a supportive role in vascular maintenance and regulation of angiogenesis, as well as putative roles in inflammation and immunity. Indeed, platelets are now linked to such diverse physiologic and pathologic processes as wound healing and tissue regeneration, response to microbial infection, inflammatory diseases, atherogenesis, tumorigenesis, and metastasis.
Platelets contribute to tumor cell metastasis by mediating tumor cell adhesion and subsequent extravasation, stabilizing platelet–tumor cell emboli in the circulation, and protecting tumor cells from the host immune system. In the tumor microenvironment, platelets become activated and may release growth factors, chemokines, matrix metalloproteinases (MMPs), and inflammatory mediators, with resulting production and remodeling of the extracellular matrix and tumor angiogenesis. In this chapter, we review the role of platelets and thrombin in metastasis. We review clinical trial data with aspirin and anticoagulants in cancer and cancer prevention, and speculate on the potential effect of thrombin in unmasking tumor dormancy.
18 - Platelets in other thrombotic conditions
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- By David Green, Simon Karpatkin, Department of Medicine (Hematology), New York University School of Medicine, New York, NY, USA, Peter W. Marks, Yale University School of Medicine, New Haven, CT, USA
- Edited by Paolo Gresele, Università degli Studi di Perugia, Italy, Valentin Fuster, Mount Sinai School of Medicine, New York, Jose A. Lopez, Seattle University, Clive P. Page, King's College London, Jos Vermylen, Katholieke Universiteit Leuven, Belgium
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- Book:
- Platelets in Hematologic and Cardiovascular Disorders
- Published online:
- 15 October 2009
- Print publication:
- 13 December 2007, pp 308-322
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- Chapter
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Summary
INTRODUCTION
The role of the platelets in the pathogenesis of venous thrombosis is still not fully defined. Evidence suggests that platelets contribute to venous clot formation, particularly under certain circumstances. Supporting evidence comes from laboratory studies as well as from clinical trials investigating the role of antiplatelet therapy.
In addition to their well-known function in thrombosis and hemostasis, platelets also mediate vascular integrity and regulate angiogenesis. The connection between hypercoagulation, thrombosis, and malignancy is by now well established. Thrombin exerts effects on tumor cells, vascular endothelium, and platelets, enhancing tumor cell growth, adhesion, angiogenesis, metastasis, and thrombosis. Thrombin thereby potentiates the malignant phenotype and initiates a “vicious cycle.”
PLATELETS IN VENOUS THROMBOSIS
The role of platelets in arterial thrombosis has been well defined, as noted elsewhere in this volume. Under conditions of high flow or shear stress, such as those found in arterioles, collagen exposed by injury to the endothelial surface activates von Willebrand factor, which subsequently recruits platelets to the site of injury or vessel narrowing. The platelets become activated and both recruit additional platelets as well as facilitate coagulation at the site of the nascent clot. The role of the platelet in venous thrombosis is less clear. However, several lines of evidence indicate that platelets are also involved in the pathogenesis of venous thromboembolism (VTE).
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